Cytology - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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CYTOLOGY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AM ES N. P ARK ER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Cytology: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00331-7 1. Cytology-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on cytology. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CYTOLOGY ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Cytology ........................................................................................ 4 The National Library of Medicine: PubMed ................................................................................ 58 CHAPTER 2. ALTERNATIVE MEDICINE AND CYTOLOGY .............................................................. 105 Overview.................................................................................................................................... 105 National Center for Complementary and Alternative Medicine................................................ 105 Additional Web Resources ......................................................................................................... 105 General References ..................................................................................................................... 106 CHAPTER 3. DISSERTATIONS ON CYTOLOGY ................................................................................ 107 Overview.................................................................................................................................... 107 Dissertations on Cytology.......................................................................................................... 107 Keeping Current ........................................................................................................................ 108 CHAPTER 4. PATENTS ON CYTOLOGY ........................................................................................... 109 Overview.................................................................................................................................... 109 Patents on Cytology................................................................................................................... 109 Patent Applications on Cytology ............................................................................................... 137 Keeping Current ........................................................................................................................ 149 CHAPTER 5. BOOKS ON CYTOLOGY .............................................................................................. 151 Overview.................................................................................................................................... 151 Book Summaries: Federal Agencies............................................................................................ 151 Book Summaries: Online Booksellers......................................................................................... 153 Chapters on Cytology................................................................................................................. 154 CHAPTER 6. MULTIMEDIA ON CYTOLOGY .................................................................................... 159 Overview.................................................................................................................................... 159 Audio Recordings....................................................................................................................... 159 CHAPTER 7. PERIODICALS AND NEWS ON CYTOLOGY ................................................................. 161 Overview.................................................................................................................................... 161 News Services and Press Releases.............................................................................................. 161 Academic Periodicals covering Cytology ................................................................................... 164 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 167 Overview.................................................................................................................................... 167 NIH Guidelines.......................................................................................................................... 167 NIH Databases........................................................................................................................... 169 Other Commercial Databases..................................................................................................... 171 APPENDIX B. PATIENT RESOURCES ............................................................................................... 173 Overview.................................................................................................................................... 173 Patient Guideline Sources.......................................................................................................... 173 Finding Associations.................................................................................................................. 177 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 179 Overview.................................................................................................................................... 179 Preparation................................................................................................................................. 179 Finding a Local Medical Library................................................................................................ 179 Medical Libraries in the U.S. and Canada ................................................................................. 179 ONLINE GLOSSARIES................................................................................................................ 185 Online Dictionary Directories ................................................................................................... 187 CYTOLOGY DICTIONARY ........................................................................................................ 189

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INDEX .............................................................................................................................................. 263

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with cytology is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about cytology, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to cytology, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on cytology. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to cytology, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on cytology. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON CYTOLOGY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on cytology.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and cytology, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “cytology” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Brush Cytology in the Diagnosis of Neoplasia in Barrett's Esophagus Source: Diseases of the Esophagus. 10(4): 233-237. October 1997. Contact: Available from Harcourt Brace and Company, Ltd. Journal Subscription Department. Foots Cray, Sidcup, Kent, DA 14 5HP. Summary: Endoscopic esophageal brushings for cytology, in addition to biopsies for histology, are often taken from patients with Barrett's esophagus, in an effort to improve sensitivity for detecting neoplasia (cancer). This article reports on a retrospective review performed to assess the value of cytology in assessing patients with Barrett's esophagus. One hundred and sixty two patients (87 with esophageal or gastroesophageal junction adenocarcinoma, 65 with nondysplastic Barrett's esophagus, and 10 with dysplastic Barrett's esophagus) had biopsies and brushings taken for histological and cytological

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assessment. Eighty-two of 92 patients with carcinoma or high-grade dysplasia (changes in cells) had true positive malignant cytology. Seven of 65 patients with nondysplastic but inflamed Barrett's esophagus had false positive malignant cytology. One of these patients had an esophagectomy (removal of the esophagus) on the basis of cytology, but no tumor was found in the resection specimen. This translates into an 89-percent sensitivity and specificity of cytology for detecting esophageal columnar neoplasia. The authors conclude that cytology from Barrett's esophagus in the presence of severe inflammation can be misleading. Cells from a benign Barrett's ulcer may appear frankly malignant when examined in isolation. The authors stress that esophagectomy should not be performed on the basis of cytological evidence alone. 3 figures. 1 table. 13 references. (AA-M). •

Oral Exfoliative Cytology Procedures: Conventional, Brush Biopsy and ThinPrep Source: Journal of the Tennessee Dental Association. 81(1): 17-20. Winter 2001. Contact: Available from Journal of the Tennessee Dental Association. 2104 Sunset Place, Nashville, TN 37212. E-mail: [email protected]. Summary: This article compares three techniques (conventional, brush biopsy and thinprep) for oral exfoliative cytology (looking at the cells of an oral lesion without surgical biopsy). In the conventional oral cytology smear method, the suspicious oral lesion is scraped with a moistened tongue blade, a cement spatula, or a cotton tipped applicator in the clinician's office. After brief preparation in the dental office, the sample is sent to a laboratory for analysis. The author reviews the shortcomings of this technique. Recently, a newer type of oral screening procedure, the brush biopsy (Oral CDx) has been developed. In this method, lesion cells are collected by rotating a stiff nylon bristle brush against the epithelial surface and smearing on a microscope slide. This method also involves sending to a laboratory for analysis. The oral brush biopsy procedure is quite similar to conventional oral cytology smear except for a different collection device and computer assisted screening. The third option, the ThinPrep method, is a liquid based technique that can result in significant improvement in sample selection and specimen quality. This technique decreases the number of false negative diagnoses and results in a more sensitive test. The author stresses that any oral exfoliative cytologic procedure which reduces false negatives or positives would enable the procedure to be a more effective tool in screening for oral cancer, its precursors, and other specific viral and fungal diseases. With earlier detection of oral cancer by performing a follow up biopsy, patient morbidity and mortality should subsequently decline. The author contends that only the ThinPrep method provides a uniform, debris free, monolayer of transepithelial cells which can result in a more accurate interpretation of the screening specimen by an oral and maxillofacial pathologist. 4 figures. 11 references.

Federally Funded Research on Cytology The U.S. Government supports a variety of research studies relating to cytology. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable 2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to cytology. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore cytology. The following is typical of the type of information found when searching the CRISP database for cytology: •

Project Title: A CELL-BASED ASSAY TO MEASURE HCV DRUG SUSCEPTIBILITY Principal Investigator & Institution: Parkin, Neil T.; Virologic, Inc. South San Francisco, Ca 94080 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by investigator): Chronic infection with hepatitis C virus (HCV) is an important cause of life-threatening liver disease worldwide. Current treatments for HCV are poorly tolerable and incompletely effective, especially for HCV of certain subtypes (1a and 1b) that are prevalent in North America, Europe and Japan. Thus there are many pharmaceutical companies which are developing novel anti-HCV drugs. However, based on experience with other chronic viral infections such as HIV-1, antiviral drug resistance will likely be an important cause of failure of antiviral chemotherapy. Thus we anticipate the need for assays to measure susceptibility of patient-derived HCV to antiviral drugs. The goal of this project is to develop a rapid (105 per second, and can laser-irradiate specific cells leading to various outcomes including death, optoinjection, photobleaching, and molecular uncaging. This system is the foundation for the development of a new research-oriented cell analysis and processing instrument, called LEAPTM, which has the capability to implement HCS assays in a very high-throughput manner (HC/HTS). Feasibility studies are proposed to develop software and run cell-based assays to evaluate the speed of the LEAP platform in HC/HTS. The resulting platform, which also incorporates a targeted treatment laser, will enable new types of drug discovery approaches. Phase II will go on to optimize and implement various cell-based assays in biologically relevant experimental systems, resulting in data supporting this powerful new tool for drug discovery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACUTE MYOCARDIAL INFARCTION SENSOR Principal Investigator & Institution: Singh, Waheguru P.; Lynntech, Inc. College Station, Tx 77840 Timing: Fiscal Year 2004; Project Start 05-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Patients suffering Acute Myocardial Infarction (AMI) symptoms in Emergency Rooms are subjected to cardiac marker testing. These "cardiac markers" have great potential as early indicators of the presence of AMI when analyzed together for extended time periods. Traditional methods of detecting these protein concentrations such as Enzyme-Linked ImmunoSorbent Assay (ELISA) is expensive to perform, and only test one protein at a time. In a typical month, Hermann Hospital in Houston, TX submits over 9,500 samples for cardiac marker analysis. The average cost of performing these tests is $100 per sample, resulting in an expenditure of close to $1,000,000/month. With over 4,000 hospitals nationwide, this number extrapolates to an astonishing 48 billion dollars annually for cardiac marker testing. This data suggests the need for an inexpensive sensor, capable of in-house biological fluid analysis of all cardiac marker proteins: simultaneously. By combining the selective recognition element properties of Lynntech's patent-pending iprotein-imprinted conducting polymer, with a Field-Effect Transistor (FET) acting as the transducer, Lynntech, Inc. proposes to develop a hand-held, disposable cartridge sensor capable of determining the entire array of cardiac marker concentrations simultaneously. The proposed device would be a point-of-care AMI monitoring sensor, capable of relaying critical AMI cardiac markers (i.e. Myoglobin, Creatine Phosphokinase (CPK)-MB, Total CPK, CPK-MB isoforms, and Troponin I/T) statistics, thereby reducing the lag time between the onset of AMI symptoms and treatment. The proposed sensor platform circumvents the problems associated with other biological sensors such as signal drift, costs associated with expensive protein (antibody) ligands, lack of selectivity, sensitivity, biological molecule attachment to electrode surface and limited shelf-life. Lynntech has gathered a strong research team to help perform the tasks during the Phase I research effort by recruiting the help of Georgia Tech's Dr. Janata to assist in the area of FET technology and Dr. Roe, a research physician at The Duke Clinical Research Institute, to offer his expertise in cardiac marker testing. Within the $20 billion global market for in vitro diagnostics, the fastest-growing segments are "cutting-edge"

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diagnostic test systems & technologies such as molecular diagnostics, non-invasive technologies, point-of-care testing, flow cytology, and nucleic acid testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIRWAY SMOOTH MUSCLE MODULATES INFLAMMATION IN ASTHMA Principal Investigator & Institution: Panettieri, Reynold A.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: OF PROPOSED PROGRAM (Applicant's Abstract) This proposal is an interdisciplinary effort that focuses on defining the cellular and molecular mechanisms by which airway smooth muscle (ASM) orchestrates and perpetuates airway inflammation. The central hypothesis states that synthetic responses of ASM modulate airway inflammation and remodeling in asthma. Although many studies have identified mechanisms that regulate inflammatory cell trafficking and activation, few have asserted a role for myocytes in modulating airway inflammation. ASM synthetic responses are defined as secretion of cytokines, chemokines, growth factors and expression of cell adhesion molecules and matrix components. To test our central hypothesis, four Projects and three Core Units are proposed. Project 1 will characterize the molecular signaling pathways that regulate cytokine-induced synthetic responses in human ASM. Preliminary data demonstrate that selective inhibition of pathways activated by IL-1beta and TNF-alpha has differential effects on the modulation of synthetic functions by these cytokines. These findings support a central hypothesis that cytokines regulate ASM synthetic functions through the coordinated activation of diverse signaling events. Recently established techniques for the transfection and microinjection of human ASM cells will enable delineation of the precise molecular mechanisms by which cytokines activate these pathways. Project 2 will determine how cell-matrix receptors such as CD44 promote airway inflammation, remodeling and airway hyperresponsiveness (AHR) by altering ASM function. Allergen-induced AHR is markedly inhibited in mice treated with antibodies that inhibit CD44 and in CD44 null mice. However, IgE production and leukocyte recruitment were unaffected in these animals. These data support the hypothesis that local CD44-matrix interaction regulates AHR. Using genetically manipulated mice and segmental allergen challenge (SAC) models, the relative contribution of CD44 expression on hernatopoetic cells versus lung cells and the molecular basis by which CD44 modulates AHR and airway remodeling will be determined. Project 3 will define the role of G protein coupled receptor (GPCR) trafficking and signaling in modulating inflammatory responses of ASM. GPCRs play a critical role in regulating multiple ASM functions including contraction, relaxation, and synthetic function. The dynamic regulation of GPCRs results in their movement or trafficking within the cell. Recent studies support the hypothesis that such movement is controlled by multiple mechanisms and that GPCR trafficking plays an important role in regulating signaling. A comprehensive series of studies using ASM cultures and transgenic mouse models are proposed to determine the mechanisms by which GPCR localization and trafficking regulate ASM signaling and function. Project 4 will study the mechanisms by which epithelial-ASM or -fibroblast interactions foster airway remodeling and inflammation. Cultured epithelial cells from asthmatics manifest a proinflammatory, fibrogenic phenotype towards ASM cells and fibroblasts. These data support the hypothesis that epithelial cells from asthmatics secrete substance(s) that act on fibroblasts and ASM to promote the structural airway changes in asthma. Using SAC and a novel epithelial cell culture model, the factors that promote fibrogenesis and the

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signaling pathways they activate in mesenchymal cells will be determined. Three Core Units support four Projects. Core A will perform murine physiology, histology, cytology and will establish cell lines derived from wild type and transgenic mice. Core B will supply the Projects with physiological studies and clinical specimens from asthmatics and normals. Core C will provide administrative and fiscal support. Using hypothesisdriven molecular studies of genes, proteins, cells, tissues, animal models and asthmatic patients, this interdisciplinary program will also provide new insight into the pathogenesis and treatment of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANAL DYSPLASIA IN HIV+ AND HIV- MEN Principal Investigator & Institution: Wilkin, Timothy J.; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The rate of anal carcinoma among HIV positive men is 70/100,000 person years. This is higher than the rate of cervical carcinoma prior to the onset of routine cytology screening. Anal squamous intra-epithelial lesions (ASIL) are pre-malignant lesions that can be found by screening cytology analogous to cervical dysplasia. It is felt that persistent infection with oncogenic subtypes of human papillomavirus (HPV) is the most important cofactor for development of anal carcinoma. Prior to the routine use of highly active anti-retroviral therapy, screening for anal dysplasia was studied in large cohorts of predominantly white HIV+ and HIV- men who have sex with men. High rates of ASIL and anal infection with HPV were found. It is not clear how this applies to other groups of HIV+ men including minorities, heterosexual men, and intravenous drug users, and how the rate of HPV and anal dysplasia may have changed after widespread use of HAART. This study will enroll 350 HIV+ men and 200 HIV- men who are 40% Hispanic and 40% African-American. Forty percent of the HIV+ men will report intravenous drug use or sex with women as their risk behavior for HIV. A standardized questionnaire will be administered to determine past sexual behaviors. Each participant will undergo anal cytology and anal HPV testing. Those individuals with oncogenic HPV at the first test will be followed with anal cytology and HPV testing every six months for a total of two years or five exams. Each participant with abnormal cytology will undergo high-resolution anoscopy with biopsy. Factors associated with prevalent ASIL and HPV infection including immunologic and sexual parameters will be compared using logistic regression. Persistence of HPV will be defined as the time to the first negative test for HPV and will be analyzed using Cox proportional hazards model. Factors associated with persistence will be included in a multiple Cox model. The influence of HAART will be assessed in both the prevalence and prospective components by including a term in the multiple models for length of time on anti-retroviral therapy with suppression of HIV. This study will help provide important new information on which groups of HIV+ men may benefit from screening and how HAART may modify this risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ANALYSIS OF ROLE OF THE YEAST UBP6-ENCODED HYDROLASE Principal Investigator & Institution: Golin, John E.; Professor; Biology; Catholic University of America 620 Michigan Ave Ne Washington, Dc 20064 Timing: Fiscal Year 2002; Project Start 04-SEP-2002; Project End 31-AUG-2004

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Summary: (provided by applicant): In yeast, broad-spectrum resistance inhibitors is mediated by a series of membrane transporters that are members of the ABC superfamily and use ATP to power drug efflux. The genes involved include PDR5, YOR1, and SNQ2. These loci are in turn regulated by zinc cluster transcriptionfactors encoded by the PDR1, YRR1 (PDR2) and PDR3 genes. Dominant gain-of-function mutations in PDR2 cause hyper-resistance via the over expression of YOR1, SNQ2 and at least one other target. Curiously, this target requires the presence of the Ubp6 ubiquitin hydrolase. Null mutations in UBP6 create hypersensitivity to inhibitors of protein translation. Using microarray analysis, the Ubp6-dependent PDR2 target will be identified. Subsequent genetic analysis will identify other genes that work along with UBP6. This work, along with some simple molecular cytology should help determine the precise role of this hydrolase in the cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTISTS

BIOCHEMICAL

CYTOLOGY

OF

ANAEROBIC

PARASITIC

Principal Investigator & Institution: Muller, Miklos; Associate Professor; Lab/Biochemical Parasitology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-JUL-1978; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): The goal of the proposed project is to test the hypothesis that core metabolism of the medically important cavity parasites of humans, the amitochondriate Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis differs markedly from that of their human host. It will also be explored to what extent the unique and diverse "chimeric" metabolic patterns of these organisms are due to evolutionary losses or new acquisitions of enzymes. In the next grant period emphasis will be placed on two critical but essentially unexplored aspects of "amitochondriate" parasites, a) carbohydrate (glycogen) reserves and their regulation and, b) enzymes involved in electron transport, to complement accumulating data on glycolysis and its distal extensions. a) Enzymes involved in the mobilization of glucose from glycogen and of glycogen synthesis will be expressed in heterologous systems, purified and studied with biochemical methods, with special emphasis on their regulatory properties. In addition, both the sequences and physiological characteristics of the enzymes will be evaluated in comparison with existing data in order to obtain insight into their evolutionary relationships. b ) Enzymes transferring reducing equivalents from glycolytically reduced NADH and ferredoxin to diverse electron acceptors and O2 will be explored with essentially the same approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOCHEMICAL CYTOLOGY OF NORMAL AND MALIGNANT TISSUES Principal Investigator & Institution: Novikoff, Phyllis M.; Assistant Professor; Pathology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-JAN-1975; Project End 31-MAR-2004 Summary: The long-term objectives are to determine cellular origins and lineage pathways in hepatoma formation in experimental hepatocarcinogenesis rat models. The discovery of new cell types within bile ductules (basal blast-like cells, transitional cells) in rat livers during chemical carcinogenesis suggested that other stem-like cells may exist in carcinogen-treated livers besides the previously reported oval/bile ductule cells (BD) cells. The specific aims are to determine: l) the specific cells within bile ductules

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that give rise to preneoplastic nodules (PN) and that repopulate the liver; 2) the mechanisms by which BD cells migrate and invade liver cords to form PN and whether these mechanisms are similar to those utilized by malignant cells undergoing metastasis; and 3) functional properties of ductule transitional cells that have integrated into the hepatic cord. Livers from carcinogen-partial hepatectomy (PH) protocols (Solt-Farber) will be studied for the following: l) expression of proteins during migration of BD cells into sinusoids (e.g.cytoskeleton), invasion of BD cells into liver parenchyma (e.g. extracellular matrix, adhesion receptors, endothelium, matrix metalloproteinases and inhibitors) and acquisition by transitional cells of either hepatocyte or nodular differentiation markers (e.g. transporter, secretory, cell communication) and 2) the presence of point mutations in the pS3 tumor suppressor gene in BD cells and nodules. Livers will also be injected with retroviral marker gene (E.coli-beta gal lacZ nls gene) after PH step of the protocols to label replicating basal cells to determine cell lineage pathways in PN development and in liver restoration. BD cell types and their interrelations to each other and with extracellular components will be analyzed by microscopic methods (light, confocal, electron, immunocytochemistry). Laser capture microdissection microscopy will be used to isolate specific hepatic cells from liver sections for analysis of p53 gene mutations by PCR/single strand conformation polymorphism/DNA sequencing procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOMARKERS IN PHOTOTHERAPY OF BARRETT'S ESOPHAGUS Principal Investigator & Institution: Wang, Kenneth K.; Associate Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The purpose of this study is to define the role of biomarkers in photodynamic therapy of Barrett's esophagus. Barrett's esophagus is felt to be the predisposing condition for the most rapidly increasing cancer in Caucasian males. This is a randomized prospective trial to determine the effect of photodynamic therapy on biomarkers in Barrett's esophagus and to determine the role of biomarkers in predicting response to therapy. Preliminary studies have indicated that photodynamic therapy appears to be more effective in patients who do not have specific biomarkers. In addition, it appears that patients who undergo photodynamic therapy may have improvement in histology without improvement in biomarkers. Photodynamic therapy may induce mutations in certain genes even in normal appearing tissue. It is the goal of this protocol to determine the effect of photodynamic therapy on biomarkers that have been established to be predictors of progression to neoplasia in Barrett's esophagus. These biomarkers will include assessment of cell proliferation, ploidy, p53 expression, p53 mutations, P16 promoter hypermethylation, P16 loss, and P53 loss. Methods of assessment will include denaturing high pressure liquid chromatography, image cytometry, fluorescent in situ hybridization, and immunohistochemistry. Patients with and without biomarkers will be randomized to receive photodynamic therapy and a proton pump inhibitor or a proton pump inhibitor alone. Patients treated with photodynamic therapy will receive standard dosages of sodium porfimer (2 mg/kg) and photoradiation (130 J/cm fiber) using a balloon light delivery system. Patients will have their biomarkers assessed at six month intervals. Biological sampling will be done by biopsy and cytology to enhance sampling of the mucosal surface. In addition, primary cultures of Barrett's esophagus and squamous epithelium will be assessed for mutagenesis after photodynamic therapy in vitro to determine the rate of mutagenesis of p53. It is hoped that this study will help to define the role of photodynamic therapy in

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mucosal ablation of Barrett's esophagus in terms of patient selection and biomarkers that may predict response to therapy. These observations can be extended to other forms of ablative therapy in future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER CANCER AND URINARY SCHISTOSOMIASIS IN GHANA Principal Investigator & Institution: Shiff, Clive J.; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Bladder cancer in Africa is frequently associated with infection by the urinary trematode parasite, Schistosoma haematobium and has been the subject of several hospital-based studies. In fact, a recent review of the topic was unable only to quote any data on the epidemiology and associated risk factor analysis for bladder cancer in Africa. There is a need to establish the role of this condition in endemic areas, and to determine the nature and frequency of various risk factors so that public health authorities can formulate effective control strategies. Recent research has suggested that chronic inflammation due to chronic and repeated insults from microorganisms may increase oxidative stress damage in tissue resulting in genetic changes that set the stage for malignant transformation of tissue. Urinary schistosomiasis is a persistent infection of young people that becomes chronic as they age, providing a nidus in the urothelium, which may attract bacteria, viruses and other inflammation stimulants. These, in their plethora may be the source of the repeated insults that contribute to tissue hyperplasia. However, in order to establish the true public health importance of bladder cancer, it is necessary to collect epidemiological data from an endemic area. This can be done in Ghana where S. haematobium is prevalent. Using appropriate sampling procedures, within the limitation of a small grant, sufficient infected individuals can be examined with noninvasive techniques which will provide data on the prevalence and intensity of infection as well as on the existence of biomarkers of cancer and co-infections detected by urine examination. Ultrasound examination will provide evidence for lesions of the urothelium classified for magnitude. Finally where indicated, and with informed consent, invasive examination by collection of biopsy material may be necessary for verification of the nature of any lesion. Cytological examination of urine sediment and subsequent testing of tissue for proteomics analysis in later studies will provide information on the various insults occurring in the bladder and the extent of local inflammatory responses and their association with developing cancer. The study has the potential to be extended in order to consider the mechanism of genetic change and selection of oncogenes on an epidemiological basis, and to assess the frequencies with which these occur in people living in such endemic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BRAIN MATURATION: FUNCTION FOR RAPID EYE-MOVEMENT SLEEP Principal Investigator & Institution: Shaffery, James P.; Psychiatry and Human Behavior; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 01-SEP-1995; Project End 31-MAR-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER CENTER SUPPORT GRANT Principal Investigator & Institution: Varmus, Harold E.; Director and Ceo; SloanKettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 01-JAN-1977; Project End 31-DEC-2002 Summary: Memorial Sloan-Kettering Cancer Center (MSKCC) is a free-standing institution founded as the New York Cancer Hospital in 1884 and now located in the upper east side of New York City, adjacent to the health sciences campuses of Cornell University Medical College and Rockefeller University. The Center's mission is the progressive control and cure of cancer through programs of research, patient care, and education. MSKCC is dedicated to the study of cancer through a defined spectrum of laboratory research, an interactive program spanning basic and clinical science, a strong capability for basic-to-clinic technology transfer, a structured program of clinical cancer research, state-of-the art clinical programs, including in-patient and out-patient clinical care, community care focused on early diagnosis and specific cancers and a strategically selected set of priorities in population-based research that addresses issues of both local and national importance. The research activities of MSKCC are administratively organized in seven research programs: Molecular Biology, Cell Biology, Cellular Biochemistry and Biophysics, Immunology, Molecular Pharmacology and Therapeutics, Clinical Research and Cancer Prevention and Control. These Programs are supported by 13 CCSG-supported Core Facilities as well as others supported entirely by institutional resources. The Core Facilities for which CCSG support is requested are: General Animal, Animal Health, Transgenic Mouse, Glassware Washing, Media Preparation, Flow Cytometry, Microchemistry, Molecular Cytology, Analytical Pharmacology, Human Tissue Procurement, Research Pharmacy Support, Biostatistics, and Clinical Research Support. Funds are also requested for Clinical Protocol Scientific Review and Monitoring and for Development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTER FOR ECOGENETICS AND ENVIRONMENTAL HEALTH Principal Investigator & Institution: Eaton, David L.; Associate Dean for Research; Environmental and Occupational Health Studies; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2005 Summary: The theme of the Center for Ecogenetics and Environmental Health (CEEH) is "Biochemical and Molecular Mechanisms Underlying Human Variability in Response to Environmental Exposures". The interactions between genetics and environmental are complex, and defy explanation through traditional through traditional disciplinary pathways of investigation. The purpose of the CEEH is to provide an administrative infrastructure and technical support to foster the disciplinary collaborations necessary to extend basic mechanistic studies of environmental health problems to direct application in human populations. The center consists of 5 research cores: 1) Biotransformation and Disposition, 2) Carcinogenesis, 3) Reproductive and Developmental Toxicology, 4) Neurotoxicology, and 5) Cardiopulmonary Susceptibility. Each of these Cores consists of 7-10 senior investigators and 2-5 associate investigators representing several different departments and programs throughout the University. The funded research of these investigators is enhanced by 5 facility cores which provide access to: 1) electron spin resonance spectroscopy, 2) state-of-the-art molecular biology tools and resources to assist in the conduct of large scale molecular biomarker work, 3) analytical cytology techniques such as flow cytometry and fluorescence activated quantitative cytometry, 4)

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support for development and maintenance of transgenic animals of value in toxicological research, and 5) molecular structure visualization. The Pilot Projects Program supports 6 exploratory research projects into innovative new ideas related to the theme of the CEEH for one year. A Community Outreach and Education provides a mechanism to disseminate important research findings of CEEH investigators to the general community, as well as a coordinating function to extend and enhance existing community education programs to include more emphasis on issues related to environmental health sciences. An Ethical, Legal & Social Issues (ELSI) core is being proposed which will explore the ethnical, legal and social issues surrounding the area of public health genetics and human genome research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLEX GENETICS OF D-M INCOMPATIBILITIES Principal Investigator & Institution: Hartl, Daniel L.; Professor of Biology and Chairman; Organismic & Evolutionary Biol; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Hybrid male sterility factors are the key to understanding speciation in animals and the molecular basis of Haldane's rule that impaired reproduction of the heterogametic sex is the first stage in reproductive isolation. The Dobzhansky-Muller model for the origin of reproductive isolation assumes that separated conspecific populations undergo independent gene substitutions which, when combined together in the hybrid, result in hybrid sterility or inviability. Virtually nothing is known about the genetic or molecular basis of hybrid incompatibility factors. A succession of sex-ratio meiotic drive systems and their suppressors that remodel spermatogenesis has been suggested as one mechanism associated with hybrid male sterility in Drosophila. In this amended proposal, we focus on the refined genetic mapping, positional cloning, sequencing, molecular analysis and evolutionary studies of at least 5-6 hybrid male sterility factors on the right arm of chromosome 3. These have each been mapped to approximately 1-2 cM regions using genetically marked P-element transgenes present at many different locations in chromosome 3 of D. mauritiana. These marked genomic regions have been introgressed into a standard genetic background of D. simulans and the homozygous introgression hybrids tested for fertility. Across the third chromosome, 19 factors are associated with hybrid male sterility in suitable genetic backgrounds. One of these factors, denoted tmy, is associated not only with severely reduced hybrid male fertility but also with sex ratio meiotic drive. Using a novel genetic mapping strategy that allows easy phenotypic identification of recombinants with an exchange in the region of interest, the tmy gene has been mapped to a region of 10 kb or smaller. This same mapping strategy will be used to refine the map positions of the other hybrid male sterility factors, which will have sufficient resolution to support positional cloning. Each hybrid male sterility factor will be cloned and sequenced and its molecular organization determined, and if feasible will be used for germline transformation rescue. The tmy system will be analyzed in detail cytologically. Preliminary evidence suggests a high rate of second-division Y chromosome loss and fragmentation. Downstream functional analysis of the other hybrid male sterility factors is beyond the scope of the present proposal but is of course a long-range goal. Each of the 5-6 hybrid male sterility factors that will be isolated will be subjected to an evolutionary analysis for its rate and pattern of molecular evolution, using phylogenetic analysis, polymorphism and divergence analysis between D.

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melanogaster, D. simulans and D. mauritiana, and intrapopulation analysis of polymorphisms and haplotypes to look for evidence of recent selective sweeps. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CELL AND TISSUE ANALYSIS Principal Investigator & Institution: Lein, Pamela J.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Description (provided by applicant): The Cell and Tissue Analysis Core Facility (formerly Histopathology) was established in 1986 in response to the need of Center investigators for plastic glycol-methacrylate (GMA)-embedded tissue sections for histopathologic evaluations. The plastic tissue sections (1-2 um thick) enable a resolution halfway between standard paraffin-embedded sections and sections observed under low magnification in an electron microscope. In GMA sections, cells and cell components not readily seen in standard paraffin-embedded sections can be easily visualized [e.g., mast cells and basophils (and their granules), capillary endothelial cells and pericytes, and basement membranes]. Since its inception, this Core Facility has expanded the services offered to Center investigators to accommodate the growing need for expert assistance with immunocytochemical analyses of tissue samples and cultured cells as well as the preparation of publication quality photomicrographs. In the advent of the sequencing of the human genome and the rapid advances in genomics, proteomics and metabonomics, it is becoming clear that determining the physiological relevance of these global changes in DNA expression will require imaging of these molecular changes at the level of cells and tissues, using techniques such as in situ hybridization, tissue arraying, FRET, FRAP and imaging of green fluorescent protein (GFP)-labeled proteins in live cells. Thus, the investigators anticipate that the need for the Cell and Tissue Analysis Core Facility will continue to grow in the future. The Core provides: 1) a wide range of histological and cytological services; (2) photographic and digital imaging; and, (3) professional consultation to NIEHS Center members and those in their laboratories. Through the Core facility, Center investigators also have costeffective access to equipment and services available through the Johns Hopkins University School of Medicine Microscopic Facility. The Core Facility Directors and staff also keep abreast of new developments in histopathology, cell imaging and digital photography and help Center investigators choose and develop the appropriate techniques for their research projects, analyze and interpret their data, and ultimately organize and prepare their results for publication and presentation. The overall objective of the Cell and Tissue Core Facility is to provide histopathology and cell imaging services, so that pathophysiological and toxicological investigations will be backed by morphological data at both the level of cells and tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--CELL BIOLOGY Principal Investigator & Institution: Leopold, Philip L.; Assistant Professor; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: This Program Project represents a cohesive group of laboratories and investigators that share common goals and strategies focussing on the use of adenovirus-mediated gene therapy to the respiratory tract as a therapeutic tool for treating cystic fibrosis. These laboratories also share a need for several techniques

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including morphological analysis of data generated by gene transfer studies and specialty techniques for growing handling, and analyzing cell cultures to which genes are transferred. The Cell Biology Core provides to the investigators a variety of imaging and detection methods and specialty cell culture techniques to study interaction of vectors with target cells, expression of vector-encoded transgenes, and the physiological impact of transgene expression. Toward this end, the Cell Biology Core maintains stateof- the-art equipment for fluorescence and brightfield image acquisition, documentation, and presentation and facilitated aces to additional medical center resources such as histological, ultrastructural, and confocal facilities. The staff of the Cell Biology Core has extensive training in a variety of cytological, and cell culture techniques and will dedicate time and resources to make those assets available to the participating projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CELL IMAGING Principal Investigator & Institution: Piston, David W.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The Cell Imaging Core provides access state-of-theart equipment for optical and electron microscopy and also provides expert training and consulting on the use of these methodologies. The facility maintains digital and confocal fluorescence microscopes, transmission and scanning EMs, and associated image processing and output systems. The addition of research electron microscopy was accompanied by improved equipment and expertise for specimen preparation (for both optical and electron microscopy). The staff provides effective and accessible instruction to facilitate development of functional imaging skills for all users. Scheduled access for equipment and expert assistance is done by a convenient web page interface. Because modern microscopy and digital imaging involve a large number of technical components from optics to software to chemistry, the Cell Imaging Core maintains an active development program to keep the instrumentation and systems current, functional, accessible, and easy to use. Individual researchers could not support this type of high-quality microscopy in their own labs due to the high cost of the instrumentation and maintenance and because the requisite expertise is uncommon. In addition, the Core has developed significant expertise directly related to digestive disease research: from imaging methods for intact crypts to in vivo analysis of blood and fluid flow in rodents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--IMMUNOLOGY Principal Investigator & Institution: Morris, Lynn; University of Kwa Zulu-Natal Private Bag X01, Scottsville Durban, Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Description (provided by applicant): The CAPRISA Immunology Core will perform viral characterization, humoral and cellular immunity assays, HLA genotyping and" macrophage resistance assays in three separate laboratories at the National Institute for Virology in Johannesburg and the HIV-1 Molecular Virology laboratory at the Africa Center/University of Natal in Durban. This core will meet the immunological needs of two CAPRISA projects; the acute seroconvertor project and the project involving highly exposed persistently seronegative individuals. To perform the assays needed by both projects, the core has four components: Viral characterization and humoral immunity

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laboratory led by Core Leader, Lynn Morris; Cellular immunity laboratory led by Core co-Leader, Clive Gray; HLA genotyping laboratory led by Core co-Leader, Adrian Puren; and Macrophage function laboratory led by Core co-Leader, Sharon Cassol. The humoral immunity laboratory will be involved in virus isolation and characterization as well as an assessment of neutralizing antibody activity to both autologous and heterologous viruses. Envelope genes of isolates of interest will be cloned and used in transient expression systems to more clearly define their activity. Envelope genes will be sequenced to determine what genetic changes are associated with changes in co-receptor usage or resistance to virus neutralization. The cellular immunity laboratory will establish methodologies to assess the breadth and magnitude of CD4+ and CD8+ T cell responses. Gamma interferon ELISPOT assays will be used from freshly isolated PBMC to screen for peptide and optimal epitope responses. Flow cytometry (FACS) will be used to identify specific CD4+ and CD8+ T cell IFN-g responses to either pools or single peptides. Simultaneous DNA ploidy analysis on gated CD4+ T cells will be used to assess T helper cell responsiveness to a range of HIV-1 subtype C-derived proteins and peptides. T cell lines and clones will be grown in the cellular immunity laboratory and used to map CTL epitopes. To achieve CTL epitope mapping, all B cell lines will be HLA genotyped at high resolution by the HLA laboratory. The HLA laboratory will assist in defining the HLA-restriction and identifying epitopes, performing typing at both low and high resolution by sequence specific primer (SSP)-PCR and automated sequencing, respectively. The macrophage function laboratory in Durban will work closely with the cellular immunity laboratory at the National Institute for Virology to examine the role of macrophages in resistance to HIV-1 infection. Activation and functional status of monocyte-derived macrophages and dendritic cells will be assessed. Cytokine/chemokine expression patterns will be examined by flow cytometry, RNase protection, ELISA and cytology. Activation of signaling cascades will be examined. PCR-based assays will be performed to determine if pre-integration or integrated DNA, or early and late mRNA transcripts are present in macrophages. The CAPRISA investigators involved in this core will also participate in the training program as outlined in the administration core. In this regard, the core will work in collaboration with three US laboratories based at the University of Washington (Julie McElrath) on the highly exposed persistently seronegative individuals project and Duke University on humoral immunity assays (David Montefiori) and CTL assays (Guido Ferrari). The assays undertaken by the four components in this core will determine which responses correlate with viral control and viral escape in the acute seroconvertor project and potential reasons for the phenomenon of immunological resistance to HIV-1 in the highly exposed persistently seronegative individuals project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--LABORATORY FACILITY Principal Investigator & Institution: Meiselman, Herbert J.; Professor and Vice-Chair; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: It is proposed to establish a Laboratory Core in order to support the research activities of the University of Southern California Comprehensive Sickle Cell Center (USC CSCC). This proposed Laboratory Core represents a consolidation of three ongoing activities of the present USC CSCC: 1) Biorheology-BiophysicsCore [H.J. Meiselman, PI]; 2) Diagnostic Laboratory [C.S. Johnson, Director]; 3) Haplotype Laboratory [A.L. Hiti, Director]. The specific aims of the Laboratory Core include: 1) For Project 1 (Dr. T. Fisher, PI), to provide relevant RBC rheologic and morpholgic data as

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aids in defining relations between blood group polymorphismsand specific markers of disease severity; 2) For Project 2 (Dr. C. Johnson, PI), to provide relevant RBC morphologic and rheologic data, specific ELISA assays, and RBC FACS analyses in support of studies exploring pulmonary hypertension; 3) For Project 3 (Dr. T. Coates, PI), to provide rheologic/morphologic data, biophysical techniques, and specialized hematological measurements in support of studies examining hypoxia-flow relations; 4) For Project 4 (Dr. P. Malik, PI), to provide hematological and rheological analyses for mouse and human RBC, hemoglobin analyses, and specific FACS assays, to help characterize RBC populations; 5) For Project 5 (Dr. V. Kalra, PI), to provide biophysical and rheological techniques such as RBC density fractionation and cyclic deoxygenation to aid studies of mechanisms of alveolar damage; 6) For all investigators associated with the USC CSCC, to provide relevant laboratory consultation, and to provide reference laboratory and consultative services to the local and regional medical community. It should be noted that this Laboratory Core represents a new, integrated approach to providing biochemical, biophysical, hematological, and rheological information to Center researchers. It is thus anticipated that this Core will increases the understanding of the patho-physiological events occurring in sickle cell disease, thereby leading to improved patient care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MOLECULAR CYTOLOGY FACILITY Principal Investigator & Institution: Novifoff, Phyllis; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 15-MAY-1990; Project End 31-MAR-2007 Summary: (provided by applicant): The Molecular Cytology Core will continue to provide a comprehensive state-of-the-art morphologic facility to study structure and function of liver cells. It will analyze chemical and antigenic properties of subcellular membrane compartments as well as the functional properties of subcellular compartments and their interrelationships. Light, electron and confocal microscopic techniques will be used to analyze the different levels of complexity of liver cells, in combination with methodologies that label specific macromolecules of the intra-and intercellular membrane systems and of the nucleus. Because of the variety of microscopes and in situ methods available in the facility, liver cells can be studied at different levels of organization, i.e., from their overall topology to their subcellular membrane properties and macromolecular composition in both the living and nonliving state (after fixation). The advantage of analyzing liver cells by in situ procedures is that cellular and subcellular architecture is maintained and properties of membrane systems and their interrelations in intact cells can be directly observed in real time or as fixed by preservatives at specific times. This approach reveals information regarding the organization and function of membrane and cytoskeleton compartments in cellular events that may be lost when cells are fractionated. The Director of the Molecular Cytology Core has a broad background regarding the basic cell biological processes that occur in the liver. She provides the Program investigators with technical expertise and with valuable guidance in the design and execution of their studies. She also provides interpretation of the microscopic observations for investigators as required. The Director oversees the daily activities of the personnel in the Core as well as assigning them to specific projects as needed, according to their expertise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--MORPHOLOGY/PATHOLOGY CORE Principal Investigator & Institution: Suzuki, Kinuko L.; Professor of Pathology and Laboratory Me; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: The Morphology/Pathology Core (MPC) has now been in existence for the past five years. The purpose of this core since its inception is to provide basic morphological services, consultation in experimental plans related to morphology and pathology, basic morphological services and assistance in the interpretation of experimental results. Services provided include assistance in obtaining human brain specimens, gross dissections, routine and special nervous system histology staining. Highly specialized staining techniques are also offered, including immunostaining, histochemistry, in situ hybridization, and quantitative autoradiography. Over these past five years, the number of investigators utilizing this facility are not quite the numbers anticipated in the original application. In spite of this, there has been a relatively constant utilization, from a low of five to a high of seven investigators each with multiple supported grants utilize this core facility. Since the inception of this core an impressive number of research slides have been processed. In an attempt to not overutilize the technical staff of this core and to avoid prolonged processing delays, over 21 research technologists, fellows, or students from laboratories utilizing this core have been trained in the various aspects of tissue preparation, sectioning and staining. Individual training time was from one hour to 57.5 hours. Activities taught included prepare tissue for cryostat sectioning, use of routine laboratory microtome, stain slides, and finally thin section tissues and examine by electronmicroscopy. This is excellent training for new investigators, students, and fellows. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--TISSUE /PATHOLOGY Principal Investigator & Institution: Kurman, Robert J.; Professor of Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Organized collection and expert pathologic evaluation of human tissues and biologic fluids is pivotal to the translational mission of this SPORE project. Thus this Tissue/Pathology Core is designed to provide well-characterized human biological specimens to researchers participating in the Johns Hopkins Cervical Cancer SPORE and other similar research efforts. In addition to the growing need for sophisticated sample acquisition, investigators increasingly depend on Pathology support to ensure proper tissue preparation and characterization for selected studies. This Core will also provide expert pathologic evaluation of specimens and technical support. Specifically, this core will: 1. Obtain written informed consent and collect specimens from patients for translational research without compromise of patient care or confidentiality, 2. Collect cervical carcinoma and pre-malignant lesions, as well as normal tissue, 3. Provide normal control tissue in addition to neoplasms whenever possible, 4. Process and store tissues to address the requirements of all SPORE investigators, 5. Support the development and implementation of immunologic assays, 6. Collect blood, secretions and exfoliated cells (e.g. cervical scrapes) from patients, including those enrolled in clinical trials for the SPORE projects, 7. Provide specimens that are well-characterized with respect to site of origin, pathologic grading and staging, and proportion of neoplastic and stromal tissue, 8. Provide quality-controlled specimens in a timely

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fashion as inexpensively and efficiently as possible, 9. Use well-defined mechanisms for prioritization of the distribution of requested specimens to investigators within and external to the Johns Hopkins SPORE, 10. Route specimens for virologic analyses (e.g. HPV testing and typing), immunophenotyping (e.g.HLA typing), EBV-immortalization, microarray or laser-capture microdissection in fee per service facilities. The samples are tracked using a password-protected Filemaker Pro relational database that will be web enabled for access by our off-site projects. The activities of the Resource Core will be integrated with those of the Administrative/Clinical Core and the Biostatistics and Bioinformatics Core to ensure that specimens and clinical information are appropriately catalogued and disseminated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--TISSUE CULTURE AND CELL ANALYSIS Principal Investigator & Institution: Nagaraj, Ram H.; Associate Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEFINING THE SENSITIVITY & SPECIFICITY OF BIOMARKERS Principal Investigator & Institution: Belinsky, Steven A.; Director Lung Cancer Program; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Lung cancer is the most common cause of cancer death in the United States, accounting for more life lost than breast, prostate, colon and rectal cancer combined. Of the estimated 190,000 individuals who are diagnosed each year, over 180,000 succumb to the disease. Increasing insight into the molecular basis of lung cancer pathogenesis offers hope to combat this disease. Lung cancer development and progression involves the inactivation of tumor suppressor genes and activation of oncogenes. While the accumulation of genetic alterations has been shown to be involved in the progression of lung epithelial cells from hyperplasia, metaplasia, dysplasia, carcinoma in situ, invasive carcinoma, and finally metastatic carcinoma, recent work in the previous funding period of this SPORE project has demonstrated that epigenetic changes represent another important molecular change in lung cancer. With that background, the specific aims of the current proposal are: Specific aim 1. To utilize a newly derived microarray approach to identify novel hypermethylated genes which will help comprise methylation marker panels providing for full coverage of the non-small cell lung cancer genome. Specific aim 2. To utilize the marker panels from specific aim 1 to develop an epigenetic progression model based upon studies of precursor lesions and early stage lung cancer. Specific aim 3. To test the epigenetic marker panels for their efficacy as prognostic markers to identify patients with Stage I non-small cell lung cancer at very high risk for rapid disease recurrence. case-control study comparing sputum samples from 33 incident cases and their matched controls was conducted. The presence of any of four methylation markers examined was associated with a 6.3-fold increase in the risk for lung cancer. Moderate atypia or worse in sputum was also associated with a 4.1-fold increase in the relative risk for lung cancer over this time period. Interestingly, the methylation markers and cytology were not highly correlated with each other, though each was predictive of lung cancer risk, hence the two biomarkers were synergistic in conveying a 13.8-fold increase in relative risk. Through

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this cohort and a Phase II chemoprevention trial, studies with appropriate power will be designed to test specific hypotheses related to prediction of cancer risk and monitoring of chemoprevention interventions. This project is an inter-SPORE collaboration with Colorado that links clinical and epidemiologic findings with the development of promoter hypermethylation as molecular markers through the following three specific aims. Specific aim 1 will conduct a nested, case-control study within the Colorado cohort to evaluate longitudinally the ability to detect in sputum genes inactivated by methylation as biomarkers for predicting lung cancer risk either alone or in combination. Specific aim 2 will examine the dynamics of the field cancerization process by determining the concordance between methylation changes detected in sputum and bronchial biopsies from the same subject. Specific aim 3 will determine whether a panel of methylation markers can be used to predict the efficacy of the chemopreventive agent Iloprost in a randomized Phase II study through evaluation of bronchial biopsies and sputum collected at study entry and following completion of the intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPING NEW APPROACHES FOR CERVICAL CANCER CONTROL Principal Investigator & Institution: Kiviat, Nancy B.; Chief; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Invasive cervical cancer (ICC) is an AIDS defining disease [CDC Update, 1993]. Our studies show that women with HIV-2 or HIV- I infection are at increased risk of ICC and development of cervical intraepithelial neoplasia 3/carcinoma in situ (CIN 3/CIS). Screening programs based upon cytology, detection of human papillomavirus (HPV), and visualization of the cervix have all been proposed for use in resource poor settings, however, none of these methods are practical approaches to cervical cancer control in areas of endemic HIV infection. Novel approaches must be developed to identify and treat women at high risk for ICC in HIV endemic areas. We hypothesize that, in contrast to most HIV seronegative women who are infected with oncogenic types of HPV; HIV seropositive women co-infected with oncogenic types of HPV acquired the molecular changes which permit, and are associated with progression to ICC even before cytologic changes are detected, or when only mild changes such as CIN 1 are present. We further hypothesize that such molecular changes, which are predictive of increased ICC risk can be identified and could serve as the basis for sensitive and specific assays, with high predictive value, for the early identification of HIV, infected women at high risk of ICC. Our approach to developing relevant molecular assays is based on the knowledge that the set of expressed genes, or "expression profile" of normal cells differs from that of cancer and dysplastic cells of the same tissue type [Fields, 1994]. We propose to biopsy HIV seropositive and HIV seronegative women infected with oncogenic HPV types and with varying grades of cervical lesion abnormalities (CIN 1, CIN 2/3, CIS, ICC) and examine the expression profiles of these different lesions to identify changes in gene expression that are characteristic of malignancy but occur prior to ICC (i.e., in CIS). Once such profiles are identified, we will determine and compare the frequency with which abnormally expressed genes are present in earlier precursor lesions among HIV seropositive and HIV seronegative women. Validation on additional samples, and proof of principle testing on stored longitudinal samples from women who did and did not subsequently develop CIN 3/CIS, will be performed. This will provide the rationale for future development of "low tech" ELISA assays for detection of the protein products of

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the over-expressed genes of interest and for longitudinal studies demonstrating the utility of this approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL ESTROGENIZATION OF RAT PROSTATE Principal Investigator & Institution: Prins, Gail S.; Professor; Urology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-JUL-2005 Summary: Brief exposure of rats to estrogen early in life (developmental estrogenization) leads to permanent alterations in the prostate gland and is associated with an increased incidence of hyperplasia, dysplasia, and adenocarcinoma with aging. Accordingly, it has been hypothesized that early estrogen exposure during developmental critical periods may be a predisposing factor for BPH and/or prostatic carcinoma. The long-term objectives of this investigation are to elucidate the cellular and molecular mechanisms by which neonatal estrogens initially imprint or transform the prostate gland. In the past grant periods, we have collected significant evidence to show that early estrogen exposure interrupts the process of branching morphogenesis, alters stromal cytology associated with the budding prostatic ducts and blocks certain prostatic epithelial cells from entering a normal differentiation pathway. These alterations are mediated, in part, through transient and permanent perturbations in steroid receptor expression in the prostate. Evidence also documents that TGFbeta paracrine communication between stromal and epithelial cells is interrupted following neonatal estrogenization. Preliminary evidence now leads us to hypothesize that several key developmental pathways downstream of steroid receptor action are permanently altered following estrogenic exposure. This proposal focuses on further characterizing specific developmental genes involved in prostate morphogenesis that are regulated by estrogens. The specific aims of the new proposal are: Specific Aim 1: Determine the regulatory role of fetal and neonatal estrogen on the expression of prostate homeobox genes (Hox 13 and Nkx3.1) during prostatic morphogenesis and epithelial differentiation. Specific Aim 2: Determine the effects of developmental estrogenization on secreted regulatory genes (Shh, Wnts, BMPs, Fgf) and their cognate receptors which mediate epithelial-mesenchymal communication during prostate development. Both in vivo and in vitro models will be employed to investigate the temporal and spatial expression of these developmental genes and their hormonal regulation. Methods include immunocytochemistry, in situ hybridization, laser capture microscopy followed by RT-PCR, Northern and Western analysis, receptor antagonists and micronized ligand or antibody applications. These studies are related to the normal and pathologic development of the prostate gland. Results will further define the mechanism of action of estrogen's actions on the prostate during early development and lead to a better understanding of the hormonal and developmental basis for abnormal prostatic growth with aging, particularly in the formation of prostatic adenocarcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET AND DURATION OF CERVICAL HPV INFECTION Principal Investigator & Institution: Goodman, Marc T.; Professor; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-OCT-2004 Summary: (Adapted from Investigator's Abstract) This project will establish a multiethnic cohort of women for long-term follow-up to identify factors that influence

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the persistence or resolution of human papillomavirus (HPV) infection of the uterine cervix. The specific aims are to 1) study the association of the dietary intake of fruits and vegetables, and the plasma levels of carotenoids, alpha-tocopherol, and vitamin C with HPV persistence; 2) examine the role of HPV type, quantity (viral load), and multiple (synchronous) HPV infections in HPV persistence; and 3) examine the interaction between nutritional (e.g., beta-carotene) and viral (e.g., HPV 16) factors on the risk of persistent HPV infection. A multiethnic cohort of 1,152 HPV-positive women, aged 18 and older, will be established among patients attending the obstetrics and gynecology clinics of three large medical centers in Honolulu. The cohort will include appreciable numbers of Asian (Japanese, Filipino, Chinese, Korean) Polynesian (Hawaiian, Samoan) and Caucasian women. The cohort will be followed longitudinally with the following data collected at baseline, month 4, month 8, month 12, month 24 and month 36 (6 visits): (a) a cervical cytological (Pap) smear for pathological review; (b) colposcopic visualization of the cervix for confirmation of cytology; (c) a cervical sample for HPV DNA analysis; and (d) a blood sample to measure micronutrient levels. An abbreviated questionnaire will be administered at baseline and an expanded interview will be conducted at month 4 including information on diet, tobacco and alcohol use, and sexual and reproductive history. A diet history and follow-up interview will be conducted at each annual visit. Cervical biopsy specimens obtained from cohort members will be reviewed by the study pathologist and sections will be archived at no cost to the present study. Analysis of the data will focus on the evaluation of dietary and plasma micronutrient levels and viral characteristics that influence the persistence of HPV infection using a generalized estimating equation (GEE) approach that corrects for the correlation between the repeated measures. The identification of these factors may provide insight into the natural history of HPV infection, and may improve our ability to characterize women who are at greatest risk for developing HPV-associated neoplasia. Such knowledge may also assist in the development of appropriate screening strategies involving HPV DNA detection that could be targeted at women who would benefit most from intensive follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEGREGATION

DROSOPHILA

GENES

AFFECTING

CHROMOSOME

Principal Investigator & Institution: Goldberg, Michael L.; Professor; Molecular Biology and Genetics; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-MAR-2005 Summary: (Applicant's Abstract): Mistakes in chromosome segregation during meiosis or mitosis can lead to spontaneous abortion or to abnormalities such as Down syndrome, They have also been implicated in the genetic progressions leading to cancer and aging. Our laboratory studies several genes in Drosophila that are required for proper chromosome segregation. We believe that this organism offers important advantages in genetics, genomics and cytology that provide unique opportunities to investigate chromosome behavior and cell cycle progression during cell division. We first focused on an evolutionarily conserved gene called zwlO. Mutations in zwlO not only disrupt chromosome segregation, but they also prevent the operation of the spindle assembly checkpoint that regulates anaphase onset. The ZW1O protein displays an unusual, dynamic pattern of localization during the cell cycle, moving between chromosomal kinetochores and kinetochore microtubules. We found that this pattern is influenced by bipolar tension across individual chromosomes. We also discovered that ZW1O is part of a large protein complex, one of whose activities is to target the

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molecular motor dynein to the kinetochore. The first specific aim describes further investigations on ZW1O.We will use real-time video microscopy to characterize the distribution of a ZW1O-GFP fusion protein during the cell cycle. We will determine which domains of ZW1O are required for various aspects of its intracellular distribution and function. We will analyze double mutant combinations to position ZW1O in the biochemical pathways underlying the spindle checkpoint and other aspects of anaphase onset. We will also test whether all aspects of the zw10 mutant phenotype, including its effects on the spindle checkpoint, are caused by the absence of dynein at the kinetochore. The second specific aim is to characterize biochemically and genetically the large complex of which ZW1O is a part. Preliminary efforts to purify the complex by affinity chromatography have been promising. We will use several techniques to verify the association of candidate proteins with ZW1O. We will then identify these proteins by mass spectrometry, and will determine whether they are subject to post-translational modification. Our ultimate goal is to obtain antibodies against these proteins, as well as mutations in the genes encoding them. The third specific aim will exploit our identification in the previous funding period of a set of new mutations that cause precocious sister chromatid separation, aneuploidy, or metaphase arrest in Drosophila. We will study the phenotypes associated with these mutations in more detail, clone selected mutant genes, and then investigate the intracellular location of the corresponding gene products. Because we are focusing on genes not previously known to function in any aspect of mitosis, we believe the genetic and antibody reagents obtained by the proposed studies will provide a broadened and unique view of the events occurring at anaphase onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF MECHANICAL STRAIN ON OSTEOCYTE FUNCTION Principal Investigator & Institution: Bonewald, Lynda F.; Lee M. and William Lefkowitz Professor o; Oral Biology; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: Significance: Although osteocytes make up over 90% of all bone cells, little is known about their function, compared to other bone cells, the osteoblast and the osteoclast. The osteocyte is the cell ideally situated in bone to sense mechanical strain and translate that strain into signals for bone formation and bone resorption. However, the role of osteocytes in modulating strain effects on bone modeling and remodeling is unclear: Approach: This Program Project Application was initiated to develop a time approach to clarify the mechanisms by which osteocytes sense and respond to mechanical strain in a manner that results in either bone loss, remodeling, or pathologic repair. The focus of this application is to determine the role of the osteocyte in signaling bone resorption. The mechanisms whereby osteocytes translate mechanical strain into signals include intracellular and extracellular signaling initiate or controlling osteoblast/osteoclast activity and the expression of genes necessary and specific for osteocyte function. The specific aims of the program project are: 1) determine the role and regulation of gap junction function in osteocytes, 2) to determine the levels of mechanical strains sensed by the osteocyte resulting from the mechanical stimulation of bone, 3) to identify osteocyte specific genes and their regulation by mechanical strain and 4) to determine the role of the osteocyte in osteoclast formation. Innovation: Novel approaches to answer these questions include the use of an osteocyte-like cell line, the use of bioengineering micro- mechanisms techniques to measure strain sensed by individual osteocytes, fluorescence image analysis to examine gene expression in single cells, novel animal models, and gene array technology to examine genes regulated by

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mechanical strain. Investigators and Environment: The program project is composed of investigators with specific talents, training and expertise in the areas of molecular biology, cell known for its contributions in the area of bone and cartilage biology. Knowledge gained will lead to identification of ways to regulate or inhibit the osteocytic signals of resorption that can be used towards the prevention and treatment of bone loss due to immobilization, space flight, microdamage, aging and disease states such as osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PLASTICITY

ENDOCANNABINOIDS

AND

GABAERGIC

CONTROL

OF

Principal Investigator & Institution: Alger, Bradley E.; Associate Professor; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Cannabinoids, the bioactive ingredients in marijuana and hashish, affect the brain by acting at specific, membrane bound. Gprotein-coupled receptors (CB1s). Endogenous ligands for CB1 exist (endocannabinoids), but information on receptors, receptor localization, endogenous agonists and associated second-messenger systems does not reveal the detailed workings of the endocannabinoid system, i.e., the cells that release endocannabinoids and the cells that respond to them. At the cellular level almost nothing is known about endocannabinoid release or its functional roles. Depolarization of hippocampal CA 1 pyramidal neurons releases endocannabinoids, which bind to CB 1s on presynaptic terminals of a sub-class of interneurons synapsing on them. Activation of CB1s causes a transient decrease in GABA release. This process, called DSI (depolarization-induced suppression of inhibition), represents a unique means for detecting the release and studying the actions of endocannabinoids. Using electrophysiological and optical recording techniques on hippocampal slices from normal rats and mice, and from genetically altered mice, we will test the hypothesis that neuronal excitability is governed by the endocannabinoid system. Details of the functional roles of endocannabmoids in CAl DSI remain unclear. Moreover, endocannabinoid receptors exist in other parts of the brain, and it is not known if they perform the same functions everywhere. The dentate gyrus (DG) differs from CA 1 in many ways, including neuronal circuitry and mechanisms of plasticity, such as long-term potentiation (LTP). CB 1s in the DG are associated with the same class of interneurons as in CAl. The DG is an ideal model for testing the generality of the endocannabinoid hypothesis. The DG is a gateway to the hippocampus from extrahippocampal areas and so understanding how plasticity is controlled there will be especially important. Finally, a major scientific and clinical problem is "tolerance" to the application of exogenous cannabinoids. It is not known if tolerance to exogenous cannabinoids affects the endocannabinoid system. Our Specific Aims are to test the hypotheses: 1. That endocannabinoids are necessary and sufficient to mediate DSI. 2. That endocannabinoid release facilitates NMDARdependent LTP induction in CAl. 3. That mediation of DSI is a function of endocannabinoids in dentate gyrus. 4. That endocannabinoid release facilitates induction of LTP in dentate gyrus. 5. That the development of tolerance to exogenous cannabinoids affects the endocannabinoid system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENHANCING TUMOR VACCINES WITH CO-STIMULATORY MOLECULES Principal Investigator & Institution: Kaufman, Howard L.; Associate Professor; Surgery; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The identification of tumor-associated antigens recognized by T-cells and a better understanding of how these T-cells are activated has renewed interest in the use of tumor vaccines for the treatment of cancer. The two signal hypothesis of T-cell activation states that T-cells require both an antigen-dependent signal delivered by HLA restricted epitopes and an antigen-independent signal delivered by co-stimulatory molecules. In fact, the lack of co-stimulatory molecule expression by tumor cells predicts that T-cells may be suppressed at sites of active tumor growth. This application seeks to understand the potential role of introducing costimulatory molecules into growing tumors as a method for enhancing local and systemic T-cell responses against the tumor. Recombinant poxviruses have been utilized to express human genes because of their stability, replication accuracy, and strong immunostimulant properties. The first aim is to study a recombinant vaccinia virus expressing the human B7.l co-stimulatory molecule in a dose escalation phase I trial in patients with malignant melanoma. The vaccine will be administered monthly as a direct intra-tumoral injection in an effort to activate tumor-infiltrating lymphocytes and evaluate the effects on systemic immunity. Patients will be evaluated for toxicity, clinical response, and systemic immune response by IFN-gamma ELISPOT assay. The second aim is to evaluate a novel recombinant vaccinia virus expressing three co-stimulatory molecules (B7.1, ICAM-1, and LFA-3), which has been superior to vaccinia-B7.l in preclinical studies. This vaccine will be tested in a similar dose escalation phase I clinical trial with similar endpoints. The third aim will be to evaluate the local effects of the vaccine through quantitative real-time PCR of fine needle aspirates taken from injected tumor lesions. Completion of these aims will demonstrate the safety and immunological effects of direct tumor injection of recombinant vaccinia viruses expressing costimulatory molecules. This may have important implications for the future design of tumor vaccines in melanoma and other settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESOPHAGEAL CYTOPROTECTION--AGENTS AND MECHANISMS Principal Investigator & Institution: Orlando, Roy C.; Professor of Medicine & Chief; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-AUG-2004 Summary: The long term goal of this proposal is to understand the pathogenesis of the human disease, reflux esophagitis (RE), and this approached mechanistically and from the relatively uncommon vantage point of the target tissue, the esophageal epithelium (EE). In this grant, we focus on the barrier properties of the EE, and especially that of the intercellular junctions (ICJs). The ICJs have importance as an essential defense against H+ entry into EE and as the initial target for H+ attack and damage that culminates in esophagitis. Therefore, one major goal is to characterize the barrier properties to select ions and molecules of the lumen-facing, apical cell membranes (ACMs) and ICJs using in vitro rabbit EE in Ussing chambers, and to determine how exposure to luminal acid alters these properties. Also, since many patients with RE have normal acid contact time on pH monitoring, experiments in Ussing chambered-EE are designed to identify (nonacidic) factors within the refluxate, meals and the esophageal inflammatory reaction that

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Cytology

can contibute to breaking the barriers to H+ entry into EE, and for those identified, to localize the site of action to ACMs and/or ICJs and characterize, by pH-microelectrodes, the ability to lower pHi. Further, there is evidence to suggest that patients with RE have defects in (epithelial) barrier function, and that those with nonerosive esophagitis have damage localized to the ICJs. Since localization to the ICJs is key to validating our proposed pathogenesis of heartburn and esophagitis, another goal is to confirm, using in vivo PD measurements during salt superfasions, that this defect is localized to the ICJs. Moreover, there is a high rate of relapse following medical therapy and preliminary data suggest that this is attributable to persistent defects within the EE. Therefore, we hypothesize that the defects are due to persistent esophageal inflammation and studies proposed to correlate histologic esophagitis on endoscopic biopsy with relapse frequency after cessation of medical therapy. Also, defects in epithelial defense are sought by PD measurements during acid perfusion in asymptomatic elderly Caucasian males, a group at high risk for RE, and if found, to determine if the defect is in the barrier, and age or genetics related. Another goal is to use morphology (epifluorescence/confocal microscopy, freeze fracture, TEM, immunocytochemistry). Ussing chambers and SDS-PAGE technology, to study the structure/function of the ICJs in healthy EE and to assess the mechanisms of H+ damage. This effort coupled with the studies above should provide new insights into the pathogenesis of RE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EYE RELATIONSHIPS

MOVEMENTS:

FORCE,

MOTION,

AND

ANATOMY

Principal Investigator & Institution: Goldberg, Stephen J.; Professor; Anatomy and Neurobiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 06-DEC-1995; Project End 31-JUL-2004 Summary: The exquisite precision with which the eyes acquire, pursue and fixate visual targets appears to stand in contrast to the more gross methods used to correct abnormalities in the system. Extraocular muscles (EOMs) may be surgically shortened or repositioned to compensate for inappropriate motor activity. Botulinum toxin type A can be injected in order to weaken a particular muscle so that it may perform better in relation to other muscles, although force changes after such injections have not been systematically studied. The predicted outcome of these measures can be unreliable and the interventions may need to be repeated in the same patient because it's often difficult to obtain the proper alignment of the eyes with a single procedure. While the clinical effectiveness of these strategies is unquestioned, there is obvious need to improve their precision and predictability. This proposal, using cats and monkeys, will primarily focus on two related aspects of eye movement control exposed by perturbing the normal system. I) How does EOM contractile force change from O-2 months post botulinum toxin injection and do those changes directly relate to eye displacement changes? 2) How precise are motoneuron MN firing patterns during repeated identical movements and how might that precision be altered after botulinum toxin injection? Additionally, is there a relationship between VIth nerve branching and orbital and global layer of the lateral rectus muscle? Studies of EOM electromyography (EMG), muscle immunohistochemistry and myosin expression will be carried out concurrently with the examination of these questions. The correlative evaluation of MN firing, whole muscle plus motor unit force, muscle cytology and EMG measures with eye displacement is unique and unavailable in either normal or botulinum toxin treated motor systems. It is hoped that these studies will provide information critical to clinicians seeking to

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improve patient outcomes as well as basic researchers who want to understand the complex dynamics of eye movements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS OF SILURANA TROPICALIS DEVELOPMENT Principal Investigator & Institution: Harland, Richard M.; Professor and Chair; Molecular and Cell Biology; University of California Berkeley Berkeley, Ca 947205940 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): To pursue the aims of this 'Request For Applications" we will assess the utility of Silurana (Xenopus) tropicalis for standard genetic manipulations. To date, a limited number of organisms have been exploited for forward genetic analysis. However, it has become clear that different organisms have different strengths. Our main goal in this proposal is to establish methods that will test the utility of Silurana tropicalis as an additional useful organism for genetic manipulation. A good theoretical rationale has been established, namely that the animal has a relatively short life cycle, and is relatively easy to raise in a lab setting. The embryos develop externally, and in enormous numbers, so are available for screens of early developmental defects. S. tropicalis is a tetrapod, more closely related to humans than is the fish, and therefore more useful for examination of processes such as limb development. By comparison with Xenopus laevis, a pseudotetraploid, S. tropicalis appears not to have undergone either complete or partial genome duplications, so we do not expect multiple genes to have overlapping and therefore redundant functions. In addition, the kinds of embryological experiments that can be done in Xenopus are sufficiently different from those that can be done in the fish, that the use of mutant animals will provide new information about cell and tissue interactions. We will carry out a genetic screen, map deletions cytologically, and optimize insertional mutagenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GROWTH REGULATION DURING DROSOPHILA DEVELOPMENT Principal Investigator & Institution: Edgar, Bruce A.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-AUG-1994; Project End 31-JUL-2007 Summary: (provided by applicant): This proposal is to continue ongoing studies of the cell growth control in Drosophila. We have three long-term objectives: 1) to define the cell-intrinsic mechanisms that control cell mass increase (growth); 2) to determine how cell cycle progression is coordinated with growth; and 3) to learn how patterned growth is regulated during organ morphogenesis. Four specific aims are proposed. In Aim 1 we characterize the molecular, cellular, and developmental functions of rheb, a conserved G-protein that appears to function in the insulin signaling/tuberous sclerosis (TSC)/target of rapamycin (TOR) pathway, which governs nutritionally regulated cell growth. Under this aim we also ask whether the control of ribosomal RNA synthesis is used as a means of nutritional or developmental growth control. Aim 2 proposes two forward genetic screens. One screen will select for loss-of-function suppressors of rhebmediated growth, and should identify downstream effectors in the insulin/TSC/TOR pathway. The other screen is for genes that, when over-expressed, cause clonal overgrowth in the developing eye; this should isolate several classes of genes that promote cell proliferation. Aim 3 proposes molecular tests to determine how cellular growth regulates Cyclin E and E2F to drive G1/S transitions in the cell cycle. Aim 4 applies the yield of previous aims to the problem of development. We employ epistasis

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Cytology

tests using known growth regulators, as well as gene expression profiling, to define growth-regulatory targets of the TGF-beta/BMP4 homolog, dpp, and the homeobox transcription factor, Ubx, which orchestrate patterned growth in the developing fly wing. We test the roles, in developmentally regulated growth, of dMyc, rRNA synthesis, components of the insulin/TOR signaling pathway, and others. The project as a whole makes extensive use of genetic epistasis tests, mosaic analysis, quantitative cytological assays of growth and proliferation, gene mapping, and gene expression profiling. This work will define new genes and mechanisms involved in growth control and should impact general paradigms in cell and developmental biology. It has relevance to medical conditions involving cell and tissue growth including cancer diagnosis and therapy, regeneration, wound healing, diabetes and other metabolic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH INSTRUMENTATION

PERFORMANCE

SCANNING

CYTOMETRRY

Principal Investigator & Institution: Hunter, Edward A.; Q3dm, Inc. 10110 Sorrento Valley Rd, Ste B San Diego, Ca 921211644 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 31-JAN-2004 Summary: In Phase I, the proposal aims to develop a product prototype of an incremental scanning image cytometer previously demonstrated at UCSD. In addition to instrument hardware, to be either obtained "off-the-shelf" or specially manufactured for Q3DM, the investigators will also develop software to support the image cytometer. In Phase II, the proposal aims to develop a new type of image cytometer based on continuous scanning. Phase II will culminate in shipping versions of the continuous scanning and the incremental scanning image cytometers. In addition, cell-classification tools will be developed and a multi-color fluorescence capability will be added. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH RESOLUTION 3D X-RAY DIFFRACTION MICROSCOPE Principal Investigator & Institution: Kirz, Janos; Anthropology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: The three dimensional imaging of a small cell by an extended form of X-ray crystallography (or equivalently the development and use of a soft X-ray diffraction microscope for use in cell biology) is proposed. This instrument is designed to provide three-dimensional images of frozen hydrated cellular and sub-cellular structures at better than 20 nm resolution. The instrument does not use optical elements to form the image instead it records the diffraction pattern of the coherently illuminated object, and using techniques borrowed from crystallography, performs the reconstruction using an iterative algorithm. This way the resolution is not limited by the optics, and future developments should improve the resolution limit further. The diffraction pattern from a non-crystalline specimen is a continuous (speckle) pattern. Unlike the case with crystals this pattern contains sufficient information to overcome the phase problem of crystallography by sampling the diffraction pattern at a finer scale. Undulator radiation at the National Synchrotron Light Source is used to provide coherent illumination of the specimen. The diffraction pattern is recorded using a CCD detector. Special care is taken to shield the detector from all but the desired information. A single pattern yields a twodimensional image. To obtain three-dimensional reconstruction the specimen is rotated

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and a set of diffraction patterns is collected. Frozen hydrated specimens are used to minimize the effects of radiation damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN PAPILLOVIRUS TESTING IN ADOLESCENTS Principal Investigator & Institution: Kahn, Jessica A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Jessica Kahn, M.D., M.P.H., completed clinical training in Adolescent Medicine and Gynecology at Children's Hospital, Boston and an MPH degree at the Harvard School of Public Health in 1999. She then joined the faculty at Children's Hospital Medical Center to pursue a career in patent-oriented research. David Bernstein, MD, the project Sponsor, brings expertise in clinical research regarding viraI STI, has extensive NIH funding, and has experience mentoring new investigators. The Sponsor, Advisory Board Members and Collaborators form a multidisciplinary research team with diverse expertise. The research environment will support a didactic program that includes relevant courses in advanced qualitative and quantitative methods, training in research ethics, and interaction with other clinical investigators. Dr. Kahn's overall career goal is to become an independent clinical investigator whose work will focus on the prevention of HPV infection and cervical cancer. She plans to achieve this goal through the translation of data regarding 1) the biomedical aspects of HPV infection and 2) the psychological and behavioral impact of testing for HPV into adolescent- specific, effective clinical strategies for cervical cancer prevention at the individual and population levels. The objective of this research plan is to explore the potential role of HPV testing in cervical cancer prevention programs targeting adolescents. The specific aims and methods for achieving each aim follow. Aim 1 To determine predictors of Pap smear foIlow-up in adolescents. Aim 1 will be examined using existing prospective data from a sample of 490 urban, racially diverse adolescents. Aim 2 To examine the psychological and behavioral effects of positive HPV testing in female college students. Aim 2 will be examined using existing longitudinaI data from a sample of 608 racially diverse college women. Aim 3 To explore the psychological, behavioral, and relationship-related effects of positive HPV and Pap smear testing in adolescents. Aims 3, 4, and 5 will be examined using prospectively collected, qualitative and quantitative data in a sample of 250 urban adolescent girls at high risk for HPV infection. Aim 4 To determine the accuracy and acceptability of self-testing for HPV DNA in the above sample of urban adolescent girls. Aim 5 To determine the cumulative prevalence and rates of persistence and regression of HPV infection, and correlation of HPV test results with cervicaI cytology, in the above sample of urban adolescent girls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ID-TAG PROTEIN PROFILING ARRAY FOR THE MOLECULAR CHARACT Principal Investigator & Institution: Shen, Li; Superarray Bioscience Corporation 7320 Executive Way, Ste 101 Frederick, Md 21704 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The long-term objective of this proposal is to develop a simple, reliable, sensitive, and cost-effective technological platform that will allow the simultaneous and quantitative analysis of multiple antigens in human tumor samples derived from archived tissue specimens. Such a platform is urgently needed in

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Cytology

the clinical laboratory setting to thoroughly characterize cancer. Multiplex analysis of molecular markers can augment and improve conventional methods for determining the primary anatomical site of tumor origin, predicting tumor behavior, and formulating effective therapy. SuperArray Inc.'s proprietary ID-Tag Protein Profiling technology is an antibody-based multiplex detection. Multiple ID tags are used to track multiple protein targets simultaneously. ID-tag signal can be further amplified to increase assay detection limit. Therefore, it is very promise to develop a simple clinical diagnostic tool that will be supersensitive and allow the simultaneous analysis of multiple antigens from archival material such as paraffin-embedded sections and alcohol-fixed cytology specimens. In this phase I proposal, SuperArray, Inc., will collaborate with Dr. Jian Yu Rao, Department of Pathology, University of California at Los Angeles, to evaluate the feasibility and application of the ID-Tag Protein Profiling Array technology for the molecular characterization of human cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING PATIENT SAFETY BY EXAMINING PATHOLOGY ERRORS Principal Investigator & Institution: Raab, Stephen S.; Professor of Pathology; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): A critical component of improving patient safety is reducing medical errors. A paucity of information exists on anatomic pathology diagnostic errors and their effect on patient outcomes. Many previously published studies are limited to single institutions and report variable diagnostic error percentages from less than 1 percent to 43 percent of all patients who undergo a biopsy or excisional procedure, with no correlation between error and outcome. A major goal of this project is to establish a Web-based, pathologist-driven, national, voluntary anatomic pathology error database. These data will be used for continuous quality improvement targeted at error reduction and clinical outcomes improvement. Four specific aims will be addressed. First, archival and on-going errors and their associated outcomes, detected by cytologic-histologic correlation and by secondary review of cases at interdepartmental conferences, will be identified retrospectively at four institutions and entered into the database. Each institution will enter their error data into the Web-based database on site, and the date will be sent electronically to the applicant institution for centralized analysis. Second, quarterly and annual quality performance reports, relating to these errors and outcomes, will be generated by the applicant institution research team and disseminated to each institution. These reports will include aggregate diagnostic error and outcome percentages, institution-specific error and outcome percentages, and aggregate and institution-specific error and outcome percentages stratified by multiple potential risk factors for error, such as specimen type. Quantitative analysis of these data will result in objective multi-institutional performance measures. Specific factors (e.g., specimen type, organ, clinical factors, pathologist and practice characteristics) associated with increased risk for diagnostic error will be identified. Third, root cause analysis will be performed to determine the potential sources of errors, and error reduction programs will be implemented at each institution, based on the results of the root cause analysis. Fourth, the success of these interventions will be determined by monitoring post-interventional error and the effects of error on patient outcomes. This project will provide valuable information regarding diagnostic pathology errors; it will set the groundwork for future studies focused on the

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examination of other types of diagnostic pathology error and the effect of error reduction programs in pathology practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOMETRY

IN

VIVO

IMMUNOFLUORESCENCE

MICROSCOPY

AND

Principal Investigator & Institution: Lin, Charles P.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The overall long-term goal of this multidisciplinary research program is to apply new optical technology to investigate early changes associated with cellular immune response and to monitor response to therapy over time in vivo and at the cellular level. Specifically, we proposed to develop in vivo immunofluorescence microscopy for imaging specific cell surface markers expressed by vascular and lymphatic endothelial cells, circulating leukocytes, and tissue dendritic cells. The technology that enables noninvasive, real-time cellular imaging is a video rate confocal and multiphoton fluorescence microscope that we recently developed in our laboratory. We will apply this technology to study important steps involved in the regulation of cellular immune response in vivo, including endothelial cell activation, leukocyteendothelial interaction, and dendritic cell recruitment and migration. In addition, we proposed to develop an in vivo flow cytometer, a novel technology for real-time, noninvasive detection and quantification of circulating cells that are tagged with fluorescent antibodies or antibody fragments. We will use this system to monitor changes in specific T cell population in response to immunomodulation, to detect circulating tumor cells and to investigate the correlation between tumor cell shedding and metastatic potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFRARED MICROSPECTROSCOPY FOR CERVICAL CANCER SCREENING Principal Investigator & Institution: Diem, Max; Professor; Chemistry; Hunter College Room E1424 New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): This proposal is aimed at establishing Infrared Microspectroscopy (IR-MSP) as a faster, less expensive, more objective and more accurate technology for the detection of cervical dvsplasia than presently used methods. Screening for cervical disease is presently carried out via a cytological procedure (the Papanicolaou, or "Pap" test), that was first proposed in the late 1940's [Papanicolaou, 1948]. Although regularly scheduled gynecological screening using the Pap test has reduced the incidence of, and mortality from, cervical cancer enormously, there remains a relatively high rate of inaccurate or inconclusive diagnoses [US Department of Health and Human Services, 1989]. Classical cytology is a visual inspection method based on locating and recognizing cells with altered morphology as an indicator of disease. The morphological changes are a consequence of cellular mutations. Although well established, this approach suffers from the fact that the interpretation of morphological change is human-based and therefore, subjective in nature. Furthermore, operator fatigue, training and experience influence the quality, reliability and reproducibility of cytological diagnoses. To alleviate the inherent limitation of visual inspection, computer based inspection by imaging technology has been developed and utilized over the past

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ten years. However, computer based image analysis has not significantly improved the reliability of the diagnoses, and has not proved cost effective [Hutchinson, 1996]. IRMSP is a novel technique that recognizes abnormality by detecting cellular composition and variations therein, rather than by changes in morphological features. In fact, IR-MSP detects the precursor of the morphological change. The actual measurement carded out in IR-MSP is objective and quantifiable; consequently, the diagnostic method is more sensitive, specific, reproducible and reliable than existing methods. In this proposal, the methodology for IR-MSP testing of cervical smears will be developed, including the purification of the exfoliated cells, preparation of a cell monolayer on a suitable substrate, spectral imaging of about 104 individual cells via an infrared microspectrometer equipped with a focal plane array detector, and analysis of the collected data via multivariate statistical methods to arrive at a diagnosis. This work has the potential to improve cervical cancer screening by further reducing false positive and false negative diagnoses, and introducing fast and point-of-care routine screening tests. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTEGRATED OPTICAL/MAGNETIC RESONANCE MICROSCOPY Principal Investigator & Institution: Wind, Robert A.; Staff Scientist; Battelle Pacific Northwest Laboratories Box 999, 902 Battelle Blvd Richland, Wa 99352 Timing: Fiscal Year 2002; Project Start 10-SEP-1999; Project End 31-MAY-2004 Summary: Magnetic resonance microscopy (MRM), including microscopic imaging and spectroscopy are becoming increasingly important in cancer diagnosis and treatment. Both morphometric and metabolic changes in cells can be detected with MRM which may assist in early evaluation of therapeutic response. However, the results are often ambiguous due to heterogeneity of responses and the long measuring times circumvent the potential for following dynamic cellular processes. To improve this situation, we propose to develop and test a microscope in which proton MRM and optical microscopy (OM) can be performed simultaneously to study heterogeneous mammalian cell populations. With this technology, information from OM measurments will be used to guide MRM measurements, significantly improving the speed and accuracy by which MRM measurements can be obtained. High resolution OM (fluorescent) images will be used to select a subpopulation of cells undergoing a physiological response. These OM images will then be used to guide MRM experiments such that water images and metabolite spectra are obtained from only the cells of interest within the population. In the R21 phase of this proposal, an integrated OM/MR microscope in which 2 or more monolayers of cultured human cells growing within a perfusion system will be designed, constructed and tested. Each layer will have a field of view of 1 mm2. The probe will operate in a standard wide-bore (89 mm) vertical magnet with a field of 11.7 Tesla. Our goal is that this probe will be able to determine OM images with 1.5 muM spatial resolution in seconds, and measure proton MR metabolite spectra of 1,000-2,000 randomly distributed human cells within 15-60 minutes. In the R33 phase of this research, the utility and limitations of the integrated microscope will be evaluated by examining cells undergoing apoptosis, a process of critical importance to cancer therapy. Studies will be conducted to evaluate the ability of the instrumentation to identify subpopulations of cells at early and late phases of apoptosis induced by both chemicals and expression of specific genes. The ability of OM to guide MR measurements to specific cell populations or to neighboring populations will be determined. It is anticipated that the successful development of this instrumentation will, ultimately, greatly enhance the speed, specificity and utility of noninvasive MR methods in cancer research.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRATHECAL CANCER THERAPY USING I131 NAI Principal Investigator & Institution: Wong, Franklin C.; Associate Professor, Nuclear Medicine An; Nuclear Medicine; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 04-SEP-2001; Project End 31-MAY-2005 Summary: Leptomeningeal metastasis (LM) is a difficult management problem of patients with various types of cancers. If left untreated, it is invariably fatal. There is essentially no effective treatment. Serious untoward effects are associated with current therapies including neural-axis irradiation and/or intrathecal chemotherapy. The former is limited by radiotoxicity to the underlying nervous tissues while the latter, by intrathecal breakdown and poor penetration of the meninges to reach the tumors. On the other hand, the locoregional use of radiopharmaceuticals such as beta-emitters with millimeter ranges may overcome such hurdles. Beta emission from iodine-131 has a limited range of 2-3 mm that is not impeded by diffusion. It will deliver large radiation to the tumors in the CSF and meninges while sparing the cerebral cortices and the spinal cord. Others using tumor-specific I-131 labeled anti-tenascin monoclonal antibodies have found partial therapeutic success but encountered hematotoxicity. Since hematotoxicity from I-131 compounds has been correlated with total body exposure and labeled antibodies are known to be retained in the body for days, exclusion of the antibody moiety may enhance excretion of unnecessary radiopharmaceuticals and decrease hematotoxicity to allow higher initial dosage for better efficacy. This study aims to determine the regional distribution, dosimetry, potential toxicity and efficacy of intrathecal I-131 sodium iodide (NaI). It is a widely available radiopharmaceutical for effective thyroid cancer therapy. Our preliminary modeling results have found sufficient dosimetry to treat tumor cells in the CSF and meninges, while sparing the underlying brain and spinal cord. This Phase I study will measure the whole-body, organ and regional dosimetry of intrathecally injected I- 131 NaI to correlate with potential efficacy and side effects including thyrotoxicity, hematotoxicity and neurotoxicity. Five to six groups of 3 patients will be studied according to the IRBapproved protocol ID98- 331. In brief, study patients will undergo intrathecal injection of I-131 NaI, followed by blood and urine collection and scintigraphic imaging at determined intervals for pharmacokinetics and dosimetry. Eradication of tumor cells in the CSF will be the primary indicator of efficacy. The CSF cytology, MRI, thyroid, hematology and neuropsychology profiles and neurological status will be followed up to 6 months and contrasted with dosages and dosimetry to determine a reliable set of parameters for further studies. At the end of the study period, our team shall have generated a sufficient set of data to determine whether it is worthwhile to pursue a phase II clinical trial of intrathecal I-131 NaI for the treatment of LM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LASER PHOTORADIATION THERAPY OF MALIGNANT TUMORS Principal Investigator & Institution: Berns, Michael W.; Professor; Surgery; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-MAY-1982; Project End 31-JUL-2004 Summary: The long term objective of this project is the development of Photodynamic Therapy (PDT) for application in the clinical management of patients with cancer. This goal will be accomplished by (1) gaining a more complete understanding of the basic

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mechanisms of PDT, and (2) conducting careful clinical studies in order to demonstrate safety and efficacy. The specific aims of the basic science studies are to investigate the fundamental mechanism(s) of PDT action on tumor microvasculature at two levels: (1) Human dermal microvascular endothelial cells (MEC); and (2) tumor-induced capillary proliferation in the rabbit cornea. The specific aims of the clinical studies are to determine the efficacy of PDT in Carcinoma In Situ (CIN) in the female genital tract employing topical (non-systemic) drug application. To elucidate further the mechanism(s) of PDT action on human MEC different photosensitizers will be studied with respect to: (1) cellular uptake/retention kinetics (2) subcellular localization/binding (3) subcellular phototoxicity (4) photosensitizer photobleaching and predictive value of fluorescence for phototoxicity (5) mechanism(s) of cellular uptake. Those photosensitizers that show significantly more PDT activity than PHOTOFRIN/R "standard" in the human MEC culture studies will be evaluated in the rabbit cornea model. The purpose of these studies will be to elucidate the mechanism(s) of PDT action on tumor microvasculature by examining each of the photosensitizers with respect to: (1) light and drug dosimetry parameters for optimal tumor microvasculature destruction (2) light and electron microscopic study of the time course of tumor microvasculature destruction and (3) determination of photosensitizer localization in tumor microvasculature structures using electron microscope autoradiography. Once potential photosensitizers have demonstrated photosensitizing capabilities in cell culture experiments, a determination will be made in the rabbit cornea model of the relevant light and drug dosimetry parameters necessary to produce optimal tumor microvasculature destruction. The parameters to be studied are: (1) time interval between intravenous injection of photosensitizer and light exposure (2) photosensitizer (mg/kg body weight) and total light (J/cm2) doses (3) laser irradiation: power density (mW/cm2) and spot diameter. In order to study topical drug PDT (as opposed to systemic drug injection) in a human clinical setting, a randomized, placebo controlled study in 120-140 patients with CIN II or III of the cervix will be undertaken. Eligible patients will undergo colposcopy, cytology, and photographic documentation, and colposcopic guided biopsy of abnormal lesions. One month later, a repeat colposcopy, cytology and photographic documentation will be done to assure that spontaneous regression has not occurred and patients will then be randomized to PDT or control. Response will be evaluated at 3 month intervals for up to one year post treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

LIVER

CELL

MEMBRANE

PROTEINS--EXPRESSION

AND

Principal Investigator & Institution: Wolkoff, Allan W.; Professor of Medicine; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 15-MAY-1990; Project End 31-MAR-2007 Summary: (provided by applicant): This is a Program Project to continue investigation of the function and trafficking of specific liver cell! surface membrane proteins. Four projects involving 12 faculty investigators representing ten academic departments are proposed. The first Project will characterize specific cellular components mediating vesicle trafficking and sorting. Endosomal vesicles at specific stages of the endocytic pathway as well as exocytosing Herpes simplex vesicles will be examined. Our recent development of novel fluorescence microscopy technologies should greatly facilitate these studies. The second Project has characterized genomic regulators of connexin 32, and has recently demonstrated interactions between connexins and tight junction

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proteins. Interactions with the three other Projects regarding connexin trafficking continue. The third Project is focused on the isolation and characterization of trafficking mutants in the endocytic pathway. The Trfi mutant is the original trafficking mutant that we isolated. The gene that complements this mutation has been cloned and encodes a novel Casein Kinase II catalytic subunit. A second mutant cell line has been isolated, and protocols are proposed for isolation of additional lines. The trafficking defects of Trfl have been important tools for collaborative studies with the other Projects. The fourth Project is new and is focused on hepatocellular membrane trafficking in reverse cholesterol transport. Roles for caveolin and for phosphatidylcholine transfer protein in this process will be examined. This Project was added to the Program because of collaborations that developed with the existing three Projects. This Program also provides two Core facilities. The Administrative and Supporting Services Core provides the necessary secretarial, bookkeeping, and common equipment functions. The Molecular Cytology Core provides cytochemical and morphologic services. All of these Projects are concerned with interrelated areas of hepatocyte membrane biology and pathobiology. The expertise of the investigators is complementary, and the ability to work and interact within the framework of a Program promotes the sharing of ideas, methodology, and resources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEASUREMENT OF CTL RESPONSES TO HUMAN PAPILLOMA VIRUS Principal Investigator & Institution: Anderson, Karen; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 04-AUG-2000; Project End 31-JUL-2005 Summary: (Applicant's Description): Human papillomavirus (HPV) represents a unique tumor antigen system to determine whether a cell-mediated immune response can directly alter the development of cancer. DNA from human papillomaviruses (HPV) can be found in most cervical carcinomas, and the HPV E6 and E7 gene products are implicated in cervical carcinogenesis through their interaction with p53 and Rb. An intact cell-mediated immune system is thought to be critical for control of HPV infection, since 1) the vast majority of infected HPV+ patients will spontaneously clear their infection, 2 ) the development of cervical neoplasia is HLA-linked, and 3)immunodeficiency, such as HIV infection, alters the progression of HPV infection. There are several ongoing clinical trials [involving] vaccination with HPV E6 and E7derived antigens, but many questions regarding the endogenous iLnmune response to remain to be addressed. Hypothesis: Infection of patients with human papillomavirus (HPV) subtype 16 triggers a measurable endogenous CD8+ cytotoxic T lymphocyte (CTL) response to HPV-derived peptides, and the failure to develop functional antiHPV CTL correlates with persistence of infection and progression to cervical neoplasia. To address this hypothesis, Dr. Anderson plans to accomplish the following aims: 1) Using a combination of tetramer and ELISpot assays, determine whether normal HLAA2+ blood donors have measurable and functional HPV16 E6 and E7-specific CTL, and whether these CTL can be expanded in vitro. 2) Determine if HPV16-infected patients mount an anti-HPV CTL response that inversely correlates with progression of cervical neoplasia. This will be done by enumerating, expanding, and phenotyping CTL from HPV16+ patients who have a range of cervical abnormalities, from normal cytology to cervical carcinoma. Dr. Anderson's research will be performed in a laboratory at the Dana-Farber Cancer Institute under the sponsorship of Dr. Lee M, Nadler, a leader in

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the f i eld of tumor immunology and experienced mentor of many successful physician/scientists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANICS AND DEFORMATION RESPONSES OF LUNG CELLS Principal Investigator & Institution: Hubmayr, Rolf D.; Director; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Applicant's abstract): There is overwhelming evidence that large lung deformations trigger edema and inflammation. This evidence has generated an intense debate about the choice of ventilator settings for patients with injured lungs and has fueled research on the mechanisms of ventilator-induced lung injury (VILI). The number of mechanisms and the complex interplay between them complicate analyses of experiments on whole lungs. For this reason, we propose to test our principal hypothesis (that deformation represents a pro-inflammatory stimulus for epithelial and endothelial lung cells) in whole organ as well as in reduced systems. In studies detailed under Aim 1, we will define the relationships between substratum deformation and the inflammatory signaling responses of alveolar epithelial and pulmonary capillary endothelial cells in culture. We postulate that cyclic deformation of sufficient amplitude up-regulates production and release of inflammatory mediators and consider calcium oscillations accompanying intermittent non-lethal plasma membrane stress failure events to be a possible signal transduction mechanism. Aim 2 is to underscore the biologic relevance of the cell culture work by testing in a rat model of VILI whether alveolar epithelial cells express mediators of inflammation and whether this expression requires input from alveolar macrophages. Aims 3 and 4 are to dissect the responsible mechanisms by characterizing the effects of substratum strain on cell shape and the mechanical interactions between cytoskeleton and plasma membrane. We postulate (1) that deformed cells minimize plasma membrane stress by inserting lipid molecules from intracellular stores and (2) that plasma membrane stress and the probability of stress failure vary with cytoskeletal stiffness. The recognition and transduction of deforming stresses is a rapidly expanding area of research. Much of its focus has been on membrane channel physiology and the regulation of lipid and protein mediators. The signal itself (the change in cell shape and the associated stress-distribution), the interactions between the cytoskeleton and the plasma membrane, and the implications of these interactions for plasma membrane stress failure have in comparison received little attention. This is the gap in knowledge that we intend to fill. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM OF VIRULENCE REGULATION BY MEMBRANE ACTIVATORS Principal Investigator & Institution: Dirita, Victor J.; Professor; Laboratory Animal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 15-MAR-1999; Project End 31-MAR-2009 Summary: (provided by applicant): Virulence gene regulation in Vibrio cholerae requires the action of four unusual transcription regulatory proteins, pairs of membrane localized transcription activator/effector molecules called ToxR/ToxS and TcpP/TcpH. Working models for the mechanisms of action of these proteins hold that ToxR and TcpP collaborate to activate expression of a protein ToxT, which activates genes

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encoding virulence factors cholera toxin and toxin co-regulated pilus. By contrast, ToxR alone - independently of TcpP - can regulate expression of OmpU and OmpT, two outer membrane proteins. Interactions between the activators and effectors are predicted to take place in the periplasmic space, although in general the roles of the effectors are less well characterized. TcpH acts to block a proteolytic mechanism that targets periplasmic domain of the TcpP. Whether TcpH plays any other role in the function of TcpP will be assessed in this study. FoxS may serve to confer higher order structure on ToxR essential for its function. Specific hypotheses generated from these mechanistic models of membrane-localized activator function will be tested. Much of what we understand about these proteins has come from genetic and biochemical studies, and these will continue in the work proposed herein. With advances and imaging and cytological resources available for studying the prokaryotic cell, studies aimed at developing reagents and experimental approaches for studying membrane localization of transcription complexes are also proposed. Specific Aims I. Determine the mechanism of ompU and toxT activation by ToxR. II. Determine the role of DNA binding and RNA polymerase interaction by TcpP for toxT activation. Ill. Define the mechanisms and consequences of activator/effector periplasmic interactions. IV. Develop cytological methods for analyzing membrane localized activator function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF BLADDER CANCER PROGRESSION Principal Investigator & Institution: Lokeshwar, Vinata B.; Urology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-JAN-1997; Project End 31-MAY-2007 Summary: (provided by applicant): Identification of "molecular determinants" that regulate bladder cancer (BCa) progression could improve treatment and recurrence monitoring for BCa patients. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronidase (HAase) is an enzyme that degrades HA into angiogenic fragments. HYAL1 is the major HAase expressed in bladder tumor (BT) cells. It regulates BCa growth and invasion both in vitro and in BT xenografts. While HYAL1 wild type (wt) is enzymatically active and is exclusively expressed in highgrade BCa, 5 HYAL1 variants are enzymatically inactive and expressed in normal and low-grade BCa tissues. In BT tissues, both tumor cells and the stroma produce HA, however, HAS1 type HA-synthase is exclusively expressed in BT cells. The measurement of urinary HA and HAase levels (HA-HAase test) has high accuracy in detecting BCa. This proposal is designed to investigate the therapeutic and prognostic potentials of HYAL1, HYAL1 splice variants, and HAS1 in BCa progression. Furthermore, in a multi-center trial whether the HA-HAase test, either alone or in combination with other urine tests, can be used for monitoring BCa recurrence will be evaluated. To define HYAL1 function(s) in BCa growth and progression, the efficacy of anti-HAase therapy will be tested in BT xenografts, following delivery of HYAL1antisense cDNA using a viral system or by treatment with a HAase inhibitor. The mechanism of HYAL1 action will be examined by analyzing alterations in cell cycle regulators, matrix degrading enzymes, and angiogenic factors (Aim 1). A possible neutralizing effect of HYAL1 variants on BCa growth and invasion will be examined by cDNA transfection of HYAL1wt expressing BT cells with HYAL1 splice variant cDNAs. Differential expression of HYAL1 variants in BT tissues will be correlated with BT prognosis (Aim 2). HAS1 function in BT growth and progression will be evaluated by transfecting BCa cells which either express or are blocked in HYAL1 production, using HAS1-sense and HAS1-antisense constructs. Expression of HAS1 and its variant

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Cytology

(HAS1v) in BT tissues will be correlated with BCa prognosis (Aim 3). In a multi-center trial, the utility of the HA-HAase test, urine cytology, BTA-Stat, NMP22 tests, individually and in combination, will be examined for precision to monitor tumor recurrence in 100 to 150 BCa patients. The results will be compared to clinical findings (Aim 4). The proposed study will reveal the function, therapeutic and/or prognostic potentials of the HA, HYAL1 and related molecules in BT progression. Furthermore, it will establish whether the HA-HAase test or its combination with other tests can precisely monitor BCa recurrence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEIOSIS GORDON CONFERENCE Principal Investigator & Institution: Villeneuve, Anne M.; Associate Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 028920984 Timing: Fiscal Year 2002; Project Start 05-JUN-2002; Project End 31-MAY-2003 Summary: The Meiosis Gordon Conference will be held from June 16-21, 2002 at ColbySawyer College in New London, New Hampshire. This conference will focus on research aimed at understanding the mechanisms of meiosis, the specialized cell division process by which diploid organisms generate haploid gametes. Meiosis is of central importance to sexually reproducing organisms, since precise partitioning of chromosomes during meiosis is critical for the normal development and viability of an embryo. Failure to execute the meiotic program correctly can lead to chromosomal aneuploidy, one of the leading causes of miscarriages and birth defects in humans. Further, cellular processes that are integral parts of the meiotic program, such as genetic recombination, sister chromatid cohesion, and cell-cycle checkpoint control, are also crucial for maintaining genome integrity in somatic cells. In particular, these processes repair DNA damage and prevent chromosome missegregation events that could otherwise lead to cancer. Thus understanding the control of meiosis and meiotic chromosome segregation is highly relevant both for efforts to ensure normal development of human embryos and to forestall the development of neoplasia. The Meiosis Gordon Conference will provide an opportunity for 140 scientists from throughout the world to meet and discuss the most recent developments in the meiosis field. Most attendees are principal investigators at academic research institutions, but postdoctoral fellows, graduate students and members of government and industrial laboratories will also attend. There will be about 40-45 invited speakers, whose lectures will cover all aspects of meiosis in model organisms as well as in humans. A range of approaches will be presented including cytology, genetics, cell biology and biochemistry. Plenary sessions will cover meiotic DNA replication and initiation of meiotic recombination; pathways, mechanisms and regulation of meiotic recombination; nuclear reorganization, homolog pairing and synapsis during meiotic prophase; chromosome condensation, cohesion and meiotic chromosome axes; meiotic centromeres and chromosome segregation; sessions and workshops will also provide opportunities for scientific discussion and exchange of ideas. The Meiosis Gordon Conference is one of only two regularly held meetings that concentrate on meiosis. The other meeting is held in alternate years in Europe and provides a more limited opportunity for participation, especially for scientists from the United States. The Meiosis Gordon Conference thus provides the most important forum for presenting and discussing new findings regarding a process that is central to sexual reproduction and to maintenance of genome integrity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENTORED INVESTIGATOR AWARD IN WOMEN'S HEALTH Principal Investigator & Institution: Boardman, Lori A.; Women and Infants HospitalRhode Island 101 Dudley St Providence, Ri 029052499 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The purpose of this award is to provide support for Dr. Lori Boardman to pursue formal training in the fields of biostatistics, epidemiology and public health, thereby attaining the necessary theoretical and methodological background to further a career in patient- oriented research. The final three years of the award will be devoted to the design, implementation, analysis of data and preparation of the results of a randomized controlled trial of two smoking cessation interventions in a cohort of women referred for the evaluation of abnormal Papanicolaou smears. The primary aims of this study are to evaluate smoking cessation rates between the two groups and to confirm self-reports of cessation through measurement of cervical mucus cotinine. The secondary aims are to determine the regression rate of cervical neoplasia in women who quit smoking compared to those who continue and to assess the independent and combined contribution of human papillomavirus and smoking on the natural history of atypical or low-grade cervical neoplasia (includes cytology and/or histology). This trial will be conducted with the guidance of a multidisciplinary and experienced team including experienced women's health and behavioral health researchers, epidemiologists, an oncologist, and a statistician. Immediate Career Objectives: Pursue formal training in research design and analysis by obtaining a master's degree in public health; Improve abilities to design, perform, analyze and communicate research findings through the preparation of a master's thesis and formal presentations of ongoing research stemming from clinical work in cervical neoplasia; Implement and complete a randomized trial of two smoking cessation interventions in women with cervical neoplasia. Lone-Term Career Objectives: Become an independent and productive investigator in the field of women's health care; Secure independent grant funding for patient-oriented research; Become a leader in academic medicine and mentor more junior investigators interested in women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROFLUIDIC ANALYSIS OF BLOOD CYTOLOGY AND GENETICS Principal Investigator & Institution: Gascoyne, Peter R.; Associate Professor; Molecular Pathology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR EPIDEMIOLOGY OF PERSISTENT HPV INFECTION Principal Investigator & Institution: Franco, Eduardo L.; Professor and Director; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2003; Project Start 11-SEP-1996; Project End 31-JUL-2005 Summary: (provided by applicant): This competing continuation grant is the second and last request for renewal of CA70269, the original funding for an epidemiologic study of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a low-income female population in Sao Paulo, Brazil. In collaboration with Brazilian colleagues, three of the authors began the study in 1993 in an attempt to understand

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Cytology

attributes of the natural history of HPV that could be instrumental in designing strategies for preventing cervical cancer. Considering the public health and economic importance of cervical cancer and the widespread interest in HPV vaccines and in using HPV in cancer screening there is a need for long-ranging multidisciplinary studies of the natural history of HPV. The study accrued 2529 female subjects through March 1997. Subjects have been followed up in scheduled returns every 4 months in the first year, and twice yearly thereafter for a total of 5 years. Participants undergo a questionnairebased interview have a cervical specimen taken for Pap cytology and HPV testing, and a blood sample drawn for HPV antibody serology. Follow-up will have been completed at the time current funding for the cohort study finishes in August 2002. The study's original objectives (1996-99 funding period) were: (1) to study the prevalence and incidence of persistent HPV infection in asymptomatic women; (2) to verify the hypothesis that persistent HPV infection increases risk of cervical lesions; (3) to search for determinants of persistent cervical HPV infection; (4) to search for molecular variants of HPV that may lead to an increased risk of cervical lesions; (5) to verify the hypothesis that viral burden in the cervix may be correlated with persistent infections and with lesion risk; and (6) to study the antibody response to HPV as a predictor of persistent HPV infection and of lesion risk. In the last successful continuation (1999-02 funding period) these objectives were expanded to include: (7) the search for specific HLA haplotypes associated with HPV persistence and lesion severity, and (8) to test the hypothesis that p53 gene polymorphism may influence resistance against viral persistence and to lesion development. This competing continuation is to conduct indepth statistical analyses of the database accrued during the study and to add a new objective: (9) to study the role of insulin growth factors in mediating risk of persistent HPV infection and cervical lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETICS OF TAME BEHAVIOR Principal Investigator & Institution: Kukekova, Anna V.; J a Baker Inst for Animal Hlth; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Anxiety, autism, schizophrenia, and similar problems have enormous impact on families and society. Despite their strong genetic component, their complex heterogeneous inheritance seriously constrains efforts to identify their causes. A new approach to identify genes implicated in behavioral traits in a canid model system is proposed. Two strains of silver fox (Vulpes vulpes) developed over 40 generations of selective breeding at the Russian Institute of Cytology and Genetics exhibit remarkably different patterns of hereditary behavior. The long-term goal of our project is to identify genes contributing to behavioral differences in these foxes, to enable their evaluation in human neurological and behavioral syndromes. The current proposal is essentially a pilot study, to establish proof of the principal underlying our tong term goals. Specific aims for the current proposal are to: construct a first generation meiotic linkage map of the fox genome; develop three-generation experimental backcross fox pedigrees informative for tame/friendly behavior; perform a genome wide scan to identify QTLs associated with behavioral phenotypes in these experimental fox pedigrees; and evaluate selected candidate genes for co-segregation with fox behavioral phenotypes. To achieve these aims, advantage will be taken of recent progress in canine molecular and comparative genetics. The fox meiotic map will be built by genotyping fox pedigrees with a set of canine derived microsatellites and optimized by incorporation of markers specific for genes implicated in human and/or

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rodent neurophysiology and behavior. Experimental three-generation backcross pedigrees informative for tameness will be developed by crossbreeding tame/friendly and wild type foxes, then backcrossing the F1 progeny to tame/friendly parents. Simulation studies predict power levels > 0.8 for QTL detection in the proposed genome wide scan, for all modestly optimistic scenarios. A set of candidate genes implicated in human and/or rodent behavior will be evaluated for co segregation with tame and wild type behavioural phenotypes using existing and three-generation experimental fox pedigrees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORGAN CENTER(RCMI)

STATE

UNIVERSITY

BIOMEDICAL

RESEARCH

Principal Investigator & Institution: Adams, Clara I.; Biology; Morgan State University Baltimore, Md 21251 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Description (provided by applicant): MSU has been a recipient of a Research Infrastructure in Minority Institution (RIMI) grant since 1995. As a result of the progress made in this RIMI program and other research programs, MSU has received and implemented a Ph.D. Bioenvironmental Sciences program (BSP), a M.S. and doctorate in Public Health, and several other programs. Additionally, as the number of doctoral programs increased at the institution along with the overall student enrollment, the caliber and number of faculty hired and the research productivity of the faculty has greatly increased. Therefore, in order for the institution to continue to enhance its research capacity and capabilities, MSU is requesting funds in this application to establish a Biomedical Research Center Research Centers in Minority Institutions (RCMI) program. It would focus on Stress and Cardiovascular Diseases, HIV/AIDS, Neurodevelopment/Neurodisorders and Environmental Health, as well as toxicological problems that plague our communities, our state and our nation. Consequently, the goal of this RCMI program is to further enhance the research infrastructure and research capabilities at the institution. This would be done by establishing a diverse multidisciplinary research environment that integrates information across biomedical, behavioral, and environmental health disciplines which are centered around the health concerns of the urban environment. The specific aims of this application are to: 1) amplify an administrative structure in order to enhance the efforts and accomplishments of the program s that it can interface with the ongoing university administrative structure, such that the benefits to MSU can be realized to the maximum level possible; 2) develop an Internal Advisory Committee (IAC) and an External Advisory Committee (EAC) that can provide critical advice on ways in which the investigators can enhance the research productivity of the Center; 3) establish state-of-the-art Core laboratories in the areas of histochemistry/cytology, molecular biology and environmental health/toxicology that would provide research capabilities, technical services and support to investigators addressing research questions in the areas of stress and cardiovascular diseases, HIV/AIDS, neurodevelopment/neurodisorders and environmental health and toxicological problems. In establishing these Core laboratories, the investigators plan to purchase equipment and supplies for the Core laboratories, and hire laboratory directors to direct and coordinate the activities of these Core laboratories in such a way that the research capacity that addresses the health and. health disparities identified can be enhanced; 4) provide support for graduate students who are engaged in research that addresses the health and health disparities identified above; 5) provide support for faculty pilot projects in the areas of stress and

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cardiovascular diseases, HIV/AIDS research, neurodevelopment/neurodisorders and environmental health/toxicology/biosensor research; and 6) establish an evaluation plan that addresses the formative and summative evaluation of the Center. In summary, by establishing an RCMI program at MSU, with the goals delineated in this program, the investigators will further enhance the institution's mission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NANOSTRUCTURED SUBSTRATES FOR CELL ASSAYS Principal Investigator & Institution: Israel, Barbara A.; Chief Operating Officer; Platypus Technologies, Llc 505 S Rosa Rd, Ste 150 Madison, Wi 53719 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term goal of this Phase I SBIR is to develop optimized components (nanostructured substrates) for use in the creation of a novel class of rapid, liquid crystal based cellular assays of enumeration, proliferation and function. There is a need for new technologies that are less labor intensive, consume fewer cells and reagents, can be performed in less time, allow for separation of chemotaxis from chemokinesis, provide better control over spatial and temporal aspects of the delivery of concentration gradients and are amenable to high throughput formats. Platypus Technology (tm) can be the foundation for such assays to accelerate basic cell research, drug discovery, and evaluation of anti-cancer drugs. The combination of nanostructured substrates with liquid crystals requires no labels or additional reagents to report the presence of cells. It will provide a unified platform for many diverse cellular assays. In this proposal, we will fabricate substrates with nanoscale topography by three methods: nanoscale molding, abrasion of polymeric materials and oblique deposition of thin films of gold. We will comparatively evaluate the ability of these substrates to: align liquid crystals in the presence of non-specific adsorption of proteins in cell media, support cell functions of epithelial, fibroblast and vascular endothelial cells, report cell numbers, and retain functional stability during a six-month storage period. At the completion of these studies we will have optimized the core component of a new technology for enumeration and functional evaluation of cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NATURAL HISTORY OF ANAL NEOPLASIA IN HIV INFECTED MEN Principal Investigator & Institution: Palefsky, Joel M.; Professor of Medicine; Stomatology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 25-SEP-1991; Project End 31-JUL-2004 Summary: (adapted from the Abstract): This is a re-submission of a competing renewal application for continuing support of a grant entitled "Natural History of Anal Neoplasia in HIV-infected Men" (R01 CA54053). Data from the first five years of the study show a high baseline prevalence of anal disease among HIV-positive men and a very high incidence of anal squamous intra-epithelial lesions (ASIL), including highgrade squamous intra-epithelial lesions (HSIL). With the recent advent of "highly active and retroviral therapy" (HAART), which includes protease inhibitors, possibly HIVpositive individuals will live longer, and may show a shift in the HIV epidemic from morbidity and mortality from opportunistic infections to those of more chronic diseases with a slow natural history, such as cancer. Because anal HSIL likely represents the precursor lesion to invasive anal cancer, and progression to cancer may take a number

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of years, the increased longevity of HIV-positive individuals due to HAART may, therefore, increase their risk of anal cancer. This is especially of concern given the preliminary data which suggest that the improved immune function associated with HAART does not lead to anal disease regression among men with ASIL before they began HAART. Thus, with the use of HAART a substantial number of HIV-positive men may be at risk of invasive anal cancer. In this renewal, the Investigator has three specific aims: (1) to study the natural history of ASIL and anal human papilloma virus (HPV) infection among patients on HAART; (2) to compare the natural history of ASIL and anal HPV infection to those not on HAART; and (3) to continue follow-up of the HIVpatients to define more fully the natural history of ASIL and anal HPV infection in these men. To reconstitute their cohort, this research group will recruit 350 new HIV-positive patients without HSIL and will continue to follow their existing HIV-positive and HIVnegative patients. The researchers will examine the men at 6-month intervals with an interview, an anal examination including cytology, HPV testing, and anoscopy with biopsy of visible disease. Blood will be obtained from HIV-positive patients for CD4/CD8 counts and HIV viral load at each visit. In all patients, additional anal examinations will be performed at 3-month intervals if anal disease is detected on cytology or histology. All patients diagnosed with HSIL will be referred for therapy. Similar to cervical cancer but unlike other malignancies related to HIV, invasive anal cancer is most likely a preventable disease. Because a large proportion of HIV-positive individuals will soon be on HAART, an understanding of the effect of these drugs on the natural history of anal disease and anal HPV infection will be essential in order to design a screening program for high risk individuals as well as better treatment and prevention efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATURAL HISTORY OF CIN2 IN ADOLESCENTS Principal Investigator & Institution: Moscicki, Anna-Barbara; Professor; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: This is a 5 year prospective study designed to: 1) examine the natural history of CIN-2 (cervical intra-epithelial lesions) subset of high grade squamous intra-epithelial lesions (HSIL) among adolescents, and 2) identify immunologic and behavioral factors associated with regression of CIN 2 lesions. The study of immunologic and behavioral factors that may influence CIN 2 regression will include: sustained local (cervical) Th-1 like cytokine response, systemic cytotoxic T lymphocyte (CTL) responses to HPV (for HPV 16 positive women only), size of lesion at diagnosis, amount of cervical immaturity (ectopy) at diagnosis, and hormonal contraception. Other factors that will be monitored for possible effects include high risk sexual behavior and outcomes (multiple partners, substance use, pregnancy, sexually transmitted infections, and bacterial vaginosis). Last, this study proposes to compare local immunologic responses among women who at baseline visit are diagnosed with CIN-1, CIN-2 and normal histology on biopsy. Approximately 40,000 young women 19 years or younger are expected to undergo cervical cytology screening within the Northern California Kaiser Permanente clinics over a 24 month period. Adolescents aged 13-19 years with abnormal cytology (estimated N=2680) will be recruited. Baseline examination will include interview and cervical samples for HPV DNA testing and quantitative cytokine studies using reverse transcriptase polymerase chain reaction techniques. Colpophotographs will be obtained to determine lesion size. All samples will be obtained prior to biopsy. Those with biopsy-confirmed CIN 2 (N=416) will be followed every 3 months using interview,

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colposcopy, HPV DNA testing, and cytology and undergo immune studies (cervical cell cytokine analysis using real-time RT-PCR and peripheral blood CTL assays on women with HPV 16 infection) until the end of the study. Women with CIN-3 are exited for standard therapy. Those with biopsied confirmed low grade (L) SIL or less will exited. Understanding of the natural history of CIN 2 will be critical in efforts to construct costeffective strategies for cancer screening in adolescents. In addition, defining immunologic factors associated with CIN 2 regression will have important implications for vaccine and therapeutic strategies and defining clinical (including repeated HPV DNA testing) and behavioral risks will have important implications for triage and counseling strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW TECHNIQUES FOR MICROARRAY FABRICATION AND ANALYSIS Principal Investigator & Institution: Wang, Frank F.; Biomachines, Inc. 507 Airport Blvd, Ste 107 Morrisville, Nc 27560 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Current microarray techniques are subject to inherent variability directly related to the inability of array deposition systems to accurately identify and record the location of arrayed materials and to communicate this information to follow-on systems for use in post-deposition array processing, readout and analysis. The inability to easily identify, record and communicate the accurate location of arrayed materials and any spatial distortions introduced in arrayed materials during post-deposition processing are barriers to automation and integration of array production, processing and analysis. In this SBIR Phase I proposal, Biomachines proposes innovative techniques to incorporate geometric features as "fiducial marks" on microarray and biochip substrates to provide common measurable points for all steps in fabrication, processing and analysis. The use of fiducial marks as fixed reference points will enable a device (e.g., arrayer, imager) to automatically, accurately and repeatedly: align and orient substrates, deposit materials on substrates at pre-determined locations (i.e., "targeting") and identify the location and orientation of materials previously deposited on substrates. BioMachines goal is to automate the entire microarray data extraction process, simplifying analysis software, speeding data production and significantly reducing the variability encountered microarray studies. Under Phase I funding, BioMachines will modify our existing vision guided precision placement platform, including software, to use our proposed fiducial mark technology and will demonstrate the capabilities. BioMachines fiducial mark technology will have broad applications in genomics, proteomics, bioinformatics, biochips, biosensors, cytology and other applications where there is a requirement for repeatedly locating or performing actions on features sized below a few hundred microns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL MOLECULAR PROFILING OF PROSTATE CANCER SIGNATURES Principal Investigator & Institution: Ying, Shao-Yao; Cell & Neurobiology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 18-JAN-2002; Project End 31-DEC-2006 Summary: Prostate cancer accounts for 20 percent of all male malignancies and 11 percent of cancer deaths in men in the United States. The pathogenesis of converting

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prostatic intraepithelial neoplasia (PIN) to invasive carcinoma remains obscure. The long- term goal of the proposed research is to identify stage-specific gene markers and develop automated diagnosis which will facilitate early prostate cancer detection and enhance a physician's ability to make decisions on treatment. The hypotheses to be tested are (a) cell-specific, full-length cDNA libraries from prostate cells of known pathological changes from biopsied sections, cytology specimens, micro-metastasis, etc. can be generated; (b) genes which have been identified to be involved in prostatic cancer can be identified in the generated full- length cDNA libraries, and (c) Differential expression of stage- specific gene markers can be identified in different stage- specific cDNA libraries. Our immediate goal is to generate cDNA libraries from stage-specific human prostatic cancer cells obtained from histological sections; then, we will assess the quality of the cDNA libraries by confirming the full-length of a set of genes of known size and to establish the optimal condition to generate high quality cDNA libraries; we will examine differential expression of known genes of cDNA libraries generated from these stage-specific cells and identify gene markers using microarray technology as well as correlate the differentially expressed molecular markers to different stages of prostate cancer. This proposed research is worthwhile because, to this day, microarray technologies in prostate cancer have been either based on cDNA generated from xenografts and/or fluorescence in site hybridization (FISH). However, the P.I.'s laboratory has reported a newly-developed novel method of generating cell-specific fulllength cDNA libraries from single cells and a laser-assisted preparation of single cells from human prostatic cancer histological slides. In this way, amplified messenger RNA libraries from a few tissue cells can provide molecular gene expression profiles at high resolution and in vivo analyses of cancerous gene expression in human prostate cancers is potentially feasible. These results may pave the way for a precise gene-chip diagnosis of stage-specific markers of human prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL POLYMERS FOR CELL ENCAPSULATION Principal Investigator & Institution: Yalpani, Manssur; Carbomer, Inc. 2 Olde Connecticut Path Westborough, Ma 01581 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): The incidence of diabetes mellitus in adults is on the rise globally and constitutes a major health problem. We are proposing the development of a new encapsulated glucose-responsive insulin secreting cell implants for the treatment of type I diabetes, using poly(gamma-glutamic acid) (gamma-PGA). Previously unavailable, very high molecular weight gamma-PGA will be prepared, using a proprietary process. Preliminary data from pilot studies indicate that gammaPGA constitutes a promising material and viable approach for efficacious and prolonged insulin delivery in therapeutic uses. PROPOSED COMMERCIAL APPLICATIONS: Diabetes mellitus constitutes a major health problem. Diabetes can lead to many complications, e.g., lower extremity ulcers, visual dysfunctions, and impaired wound healing. About 90% of the costs of diabetes therapy are spent on diabetes communications. Over $11 billion is spend on end-stage renal disease treatment alone. Successful development of insulin-PGA delivery systems will have a major impact on diabetes therapy. Achieving the preparation of biocompatible PGA for cell encapsulation will constitute a major milestone in the use of biopolymers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: P53 AND DNA PLOIDY IN BARRETT'S METAPLASIA Principal Investigator & Institution: Younes, Mamoun; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 09-JAN-2001; Project End 31-DEC-2005 Summary: The goal of this study is to determinewhether the accuracy and costeffectiveness of endoscopic surveillance protocols aimed at detecting early malignant transformation in patients with Barrett's metaplasia (BM) can be improved by: 1) testing the hypothesis that p53 protein accumulation, DNA aneuploidy, and increased G0G1 or G2M fractions are more accurate and objective markers of malignant potential in Barrett's metaplasia (Barrett's esophagus) than the routine morphologic evaluation of dysplasia, 2) determining whether biopsy and cytology combined are more useful than either biopsy or cytology alone, 3) determining the time period that elapses between the appearance of LGD/IND, p53 protein accumulation, and DNA ploidy abnormalities, and between the development of high grade dysplasia (HGD) and adenocarcinoma (CA), and 4) perform cost-analysis to determine whether a surveillance program can be constructed in which biopsy and cytology are utilized in conjunction with p53 and DNA ploidy determination, and is less costly than current surveillance programs. Evaluation of p53 accumulation and DNA ploidy studies will be performed on initial and follow-up biopsies and brush cytology material from at least 200 patients with Barrett's metaplasia (BM). Step sections of biopsies (Bx) will be stained with hematoxylin and eosin, Feulgen stain for DNA quantitation, and immunostained for p53 protein, p53 gene mutational analysis will be performed by direct sequencing on microdissected tissues. Each case will be then analyzed for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation and gene mutation. Cytologic preparations (Cy) will be also evaluated for dysplasia, DNA ploidy patterns by image analysis, and p53 accumulation. The data will be compiled every two years and correlated with the patients outcome, using the development of HGD and CA as end points in separate analyses, and evaluated by univariate and multivariate analysis. The sensitivity, specificity, and positive and negative predictive value of each of these markers as predictors of HGD and of CA development will be determined separately on markers detected by Bx, Cy, and by the Bx and Cy combined. These will be compared to determine whether the use of both Bx and Cy in the follow-up of patients with BM is better than Bx or Cy alone. The time between the appearance of one of the markers and the development of carcinoma will also be studied, in order to identify a period of time in which close endoscopic surveillance is both clinically warranted and cost-effective. p53 mutations will be compared with p53 protein accumulation, and with DNA ploidy and patient outcome in order to determine if there are specific mutations associated with progression to DNA aneuploidy and CA. A multi step progression model will be constructed, upon which a new surveillance program will be proposed. A cost analysis will be then performed to determine whether a molecular based surveillance program would be more costeffective than current program which is based on morphologic grading of dysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEPTIDE REGULATION OF THE CHOROID PLEXUS-CSF SYSTEM Principal Investigator & Institution: Johanson, Conrad E.; Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 20-AUG-1999; Project End 31-JUL-2004 Summary: Choroid plexus (CP) has a great impact on the neuronal extracellular fluid environment. Choroid epithelial cells secrete cerebrospinal fluid (CSF) as well as

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peptides that modulate brain development, fluid balance and repair following injury and disease. Various growth factors and neuropeptides synthesized in CP are secreted into CSF, thereby exerting endocrine-like effects on target cells in brain as well as local effects on CP. Thus, CP is both a TARGET and a SOURCE for peptides. The renewal projects focus on regulation of the CP-CSF system by peptides, specifically basic fibroblast growth factor (FGF-2) and arginine vasopressin (AVP). The main questions to be answered are: what functions of CP are regulated by FGF-2 and AVP, and how is the release of these peptides from CP to CSF controlled? Both FGF-2 and AVP have been widely implicated in CNS fluid homeostasis, and they are intimately associated with nitric oxide synthase (NOS) which generates nitric oxide (NO). The general working hypothesis is that FGF-2 and AVP, with actions mediated in part by NO, act in concert to reduce choroidal fluid turnover into CSF. Using acute and chronic experimentation in vivo with Sprague- Dawley rats, we will investigate how FGF-2 and AVP alter CP blood flow, CSF-forming capacity and epithelial ultrastructure. Moreover, the rat CP in vitro and the pig CP epithelium monolayer cell cultures will be utilized to analyze mechanisms of peptide effects on cellular organelles, ion transport, and fluid formation. Consequently, the three CP models, investigated with several methodologies, will enable a broad-spectrum analysis of how FGF-2, AVP, NO and other agent interact to regulate CP secretion. Elucidating the ability of FGF-2 and AVP to alter CSF dynamics will provide a larger picture of neuro-endocrine modulation of CNS fluids. Enhanced expression of FGF-2 and AVP in the CP-CSF system following ischemia and hydrocephalus suggests that peptides help to stabilize extracellular fluid volume and composition post-injury. Our long-term goal is to delineate the multifunctional roles of CP in brain fluid homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL OF BLOOD PROGENITORS TO FORM NONBLOOD TISSUE Principal Investigator & Institution: Eisenberg, Carol A.; Associate Professor; Cell Biology and Anatomy; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 20-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): A dynamic area in biotechnology today is stem cell research. Stem cells are the precursor cells of every tissue in the body and thus, have the potential to provide replacement tissue for diseased and damaged organs. Our studies on stem cell differentiation suggest that adult and embryonic stem cells share a similar tissue potential. Specifically, we believe that stem cells from adult mammalian bone marrow have the capacity to give rise to all mesoderm derived tissue-although this potential is never realized in the normal adult environment. Initial studies have shown, for example, that hematopoietic stem cells (HSCs) from adult bone marrow-which normally give rise to the cellular components of the blood-can develop into cardiac myocytes under conditions developed for nondifferentiated embryonic tissue to undergo cardiac differentiation. As a first demonstration of our hypothesis on the broad potential of adult stem cells, we propose to extensively study the formation of cardiac tissue from adult mouse bone marrow stem cells. The experiments outlined in this project are designed to: (I) definitively identify this cardiac competent cell population of the bone marrow, (II) examine the capacity of this bone marrow cellular subpopulation to maintain their cardiac competence following their expansion in culture, (Ill) investigate their capabilities as cardiac cells, and (IV) examine their ability to integrate into adult cardiac tissue as functional cardiomyocytes. The development of methods to

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manipulate stem cell potential will have significant future medical impact, as it will provide the means to convert stem cells to pure populations of individual cell types for replacement tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE STUDY ON VIRAL LOAD OF CERVICAL CANCER Principal Investigator & Institution: Adami, Hans-Olov H.; Karolinska Institute Stockholm, 17177 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Our long-term objective is to bring about prevention of cervix cancer through improved biologic understanding and more cost-effective screening strategies. Although human papilloma virus (HPV) infection is an established cause of cervical cancer, it is incompletely known if viral load of HPV influences progression from cancer in situ (CIS) to invasive cancer and/or interacts with genetic factors. Since clinical intervention precludes direct observation of this progression. unconventional approaches are needed. Our main specific aims are to; 1) quantify the absolute and relative risks for CIS and invasive cancer as a function of time since detected HPV and HPV 16 high viral load, 2) assess whether persistent HPV 16 high viral load is a determinant for development of CIS and invasive cancer, 3) assess whether the specific HLA DQ6/DR15 haplotype is associated with risks for CIS and invasive cancer, and if the association is mediated via a higher viral load and/or persistence of HP V. and 4) assess whether Chlamydia infection is associated with risks for CIS and invasive cancer. Building on experience from an earlier study of CIS (funded by NCI). we will take advantage of unique prerequisites in Sweden created by extensive population-based PAP smear screening documented in computerised registers. ascertainment of all incident cases of CIS and invasive cancer. and access to archival smears and tissue specimens. Using a nested design in this large study base with up to 25 years of complete follow-up, we will identify 600 women with invasive cancer, 600 women with CIS and 600 individually matched control women to each case-group. Using validated and sensitive PCR assays, the presence of viral DNA - and for HPV 16, also the viral load -will be analyzed in all available smears from each participant (on average four per individual, giving a total of about 9600 smears). HLA and C trachomatis will be analyzed in the first smear from all included women. Relative risks and interactions will be estimated by conditional logistic regression and absolute risk functions by non-parametric methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEROEPIDEMIOLOGIC STUDY OF HPV AND ORAL CANCER Principal Investigator & Institution: Smith, Elaine M.; Professor; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 24-SEP-1999; Project End 31-AUG-2004 Summary: Evidence from our recently conducted molecular epidemiology study of oral cancer suggests HPV is an independent risk factor in the development of these tumors. Human papillomavirus (HPV) infection is causally associated with greater than 95 percent of carcinomas of the cervix and is often found in other genital cancers as well as in laryngeal cancers. Because of the link between HPV and these tumors, early identification of the virus may provide a crucial marker of high-risk susceptibility and for early detection. In our recent study of oral cancer, cancer cases were significantly more likely to be detected with HPV in cytology specimens from the oral cavity

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compared with those of matched healthy controls: 30 percent v. 18 percent. Over 24 percent of the cancer cases compared with only 11 percent of the controls were infected with oncogenic mucosal HPV types whereas there was no difference between cases and controls in the frequency of detecting nononcogenic-mucosal (1 percent in cases or controls) or nonmucosal types (4 percent each group). Based on the results of our current study, we propose here to focus on the association between oral cancer and potential molecular and genetic mechanisms that are involved in HPV-induced carcinogenesis: viral gene presence and expression, viral load, susceptibility to viral infection and/or carcinogenesis due to p53 polymorphism, and alterations in viral gene expression by mutagenesis and/or integration. The aims of this study are to: 1) determine whether oral carcinomas harbor and express DNA genomes of oncogenic mucosal HPV types and whether HPV types/variants found in oral cancer biopsies match those in oral cytology specimens as potential markers in clinical screening; 2) characterize the potential influence of polymorphism in the tumor suppressor gene p53 on the susceptibility to HPV infection and/or oral carcinogenesis; and 3) evaluate the potential role of altered HPV gene expression due to mutations in the viral control region or due to viral DNA integration in the cellular genome in oral cancer development and progression. This study (a collaboration between clinicians, molecular epidemiologists and pathologists who are members of the U. Iowa Cancer Center) will elucidate the molecular and genetic mechanisms involved in HPV-associated carcinogenesis in the oral cavity and identify potential markers of early diagnosis and/or prognostic indicators of oral cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SINGLE-STEP DETECTION OF RNA IN CELLS Principal Investigator & Institution: Pasloske, Brittan L.; Director of Research Operations; Ambion, Inc. Austin, Tx 787441832 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The overall goal is to develop a "Cells-to-Signal" assay in which a single reagent is added to cells and then used directly for the detection of a specific RNA sequence. The Cells-to-Signal assay will be especially useful by pharmaceutical companies in drug discovery for the high throughput screening of multiple compounds for their effects on the transcription of specific genes. The major challenge will be developing this technology to be compatible with whole blood. Additionally, when paired with a portable device, this technology will have strong potential as a point-of-care diagnostic. In phase I, we demonstrated that this assay was quantitative up to 1000 cells/mu l with cultured cells. In phase II, we will develop complete systems to support the rapid screening of cultured cells in 96- and 384-well formats and to develop assays that are compatible with whole blood. A large component of this research will be to implement methods that prevent genomic DNA detection. Also, various strategies will be tested for their ability to increase the dynamic range of this assay, thereby improving its overall robustness. PROPOSED COMERCIAL APPLICATION: This technology will greatly expedite high throughput screening assays by pharmaceutical companies measuring the effects of compounds on the expression of specific genes. It also has great potential as a point-of-care diagnostics. Kits sold to basic researchers will value its ease of use and speed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SYSTEMS BIOLOGY OF CELL DECISION PROCESSES Principal Investigator & Institution: Sorger, Peter K.; Associate Professor; Biology; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The remarkable complexity of biological systems demands a systematic approach to their analysis. The goal of this proposal is to establish an MIT Center of Excellence in Cell Decision Processes (CDP) around an interdisciplinary team of cell biologists, computer scientists and microsystems engineers tackling the systems biology of protein networks and signal transduction in mammalian cells. The basic hypothesis of the CDP Center is that understanding cell decision processes requires the development of network models that combine quantitative rigor with molecular detail. These models will be hybrids containing highly specific representations of critical reactions and abstract representations of the system as a whole. Effective models will endure and capture the accumulation of knowledge over time in a rigorous and portable format. The CDP Center will follow a research paradigm that links systematic experiments and numerical modeling in a four-step feedback loop of manipulation-measurement-mining and modeling. The biological focus of the Center will be the signaling events that control apoptosis. The measurement of protein concentrations, modification state and activity will be undertaken for signaling molecules at many points in the apoptotic network. The measurements will then be analyzed using several modeling approaches ranging from highly specified to highly abstract. To collect sufficient data for systematic modeling, the CDP Center will automate and standardize biochemical methods, develop compact array-based assays and design novel microfabricated devices with integrated microfluidics and label-free sensors. To organize and systematize the data, informatic methods will be developed that support rigorous approaches to inference. Finally, physico-chemical, structuresystems and Bayesian models will be used to generate biological hypotheses for experimental verification. The research activities of the CDP Center will be complemented by graduate and undergraduate education and by an outreach program targeted at the scientific community in general and minority-serving institutions in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TARGETED PRODRUG THERAPY OF LIVER CANCERS Principal Investigator & Institution: Kuo, Macus T.; Professor; Molecular Pathology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Hepatocellular carcinoma (HCC) and advanced colorectal cancer (CRC) are among the most deadly diseases of mankind. CRC is the second leading cause of cancer-related death in the United States, mostly due to metastases. Hepatic metastases are the main threat for successful treatment of CRC. 5fluorouracil (5-FU). remains the mainstay of combination chemotherapy for nonresectable liver metastases. Recent studies have demonstrated that regional 5-FUbased chemotherapy by directly hepatic fusion showed improved response rates and survival for advanced CRC patients as compared with those undergone systemic infusion treatment. However, this delivery system is technically complicated and highly invasive. The present application describes the development of a novel delivery system for the treatment of hepatic metastases of CRC. The approach involves the use of a recombinant fusion protein consisting of malarial circumsporozoite (CS) protein, a

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hepatocyte-specific targeting ligand, linked to bacterial cytosine deaminase (CD), a "suicide gene" product which catalyzes the synthesis of 5-fluorouracil (5-FU) from its prodrug 5-fluorocytosine (5-FC). We have demonstrated in cultured cells that the CD-CS fusion protein can be internalized by a cell type-specific manner. More importantly, the internalized recombinant protein is stable for at least four weeks and exerts bystander cell killing effects upon the administration of prodrug 5-FC. The prolonged stability is probably attributed to the mechanism that the internalized fusion recombinant protein is entrapped in particular compartment(s) that are free from cytoplasmic degradation machinery. To further develop this system, we propose the following three specific aims: (A) to elucidate the mechanism(s) underlying the prolonged stability of CD-CS in cultured cells; (B) to investigate the targeting specificity, protein stability, and enzymatic activity of CD-CS in normal mice; and (C) to investigate the efficacy of CDCS/5-FC strategy in the treatment of liver metastases of colorectal cancers in animal model. We envision that the novel hepatic prodrug targeted therapy strategy proposed here, if successfully, is technically simple and non-invasive, and cost effective, therefore, should greatly improve the treatment efficacy of these life threatening diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TEM WITH DIGITAL AND CRYOPREPARATION SYSTEMS Principal Investigator & Institution: Evan, Andrew P.; Professor of Anatomy; Anatomy and Cell Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): The purpose of the application is to obtain funding to replace the existing Philips 400 TEM in the shared-user EM Center in the Department of Anatomy and Cell Biology with a state-of-the-art TEM, the JEOL 1230. The Philips 400 TEM was purchased with NSF funds in 1979 and has served over 40 different researchers over the last 23 years, but this machine is presently unreliable and outdated. Since the acquisition of the Philips 400 TEM, significant technical advances have occurred in transmission electron microscopes which include ease of use and extended capabilities like digital image recording and ultracryo-microscopy. The new TEM will be housed in a 1789 sq. ft. laboratory dedicated to electron microscopy, supervised by a full-time faculty member, Dr. Vincent Gattone and managed by a full-time, highly qualified EM specialist, Ms. Caroline Miller. The microscope will be available to all investigators within the Indiana University-Purdue University campus at Indianapolis which includes Schools of Dentistry, Medicine, Science and Engineering & Technology. However, the majority of the research projects will come from ten (10) laboratories. These investigators have been identified as "major users" of the new instrument. Dr. Robert Bacallao will employ a variety of biochemical assays for protein sorting, immunohistochemical and ultrastructural analyses of Golgi complex dysfunction following ischemic injury. Dr. Andrew Evan will use imunohistochemical and digital imaging to precisely correlate sites of renal crystal deposition with known inhibitors of stone formation. Dr. Loren Field will use TEM to correlate structural changes in cardiomyocytes after specific pathological conditions. Dr. Lincoln Ford requires digital TEM images to accurately measure changes in smooth muscle thick filaments during contractility. Dr. Susan Gunst needs digital TEM images to evaluate the cellular mechanisms that regulate the response of airway smooth muscle to mechanical forces generated during breathing. Dr. James McAteer's studies require the high resolution of the TEM to detect subtle damage to the vascular endothelium induced by shock wave lithotripsy. Dr. Bruce Molitoris will employ immunohistochemistry to determine the

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cellular, biochemical and molecular mechanisms responsible for ischemia induced membrane changes. Dr. Carrie Phillips will use immunogold EM to evaluate the cellular localization of inversin protein in the inv mutant mouse model of PKD. Dr. Zao Xu will use TEM to investigate the nature of cell death, e.g. necrosis or apoptosis, in neostriatum of the rat after transient global schemia. Dr. Richard Gregory will employ immunohistochemistry to examine the role of a Streptococcus mutans 65 kDa fimbrial protein binding as a mechanism for the induction of dental carries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE HEMATOPOIESIS

ROLE

OF

MOZ

IN

NORMAL

AND

LEUKEMIC

Principal Investigator & Institution: Snyder, Cynthia S.; Cellular & Molecular Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) Differentiating hematopoietic progenitors demonstrate an orderly maturation of chromatin, a progression that provides distinctive morphologic cues as to a cell's identity and stage of maturity. These nuclear changes, visible under the light microscope, mirror the changes in gene expression that hematopoietic stem cells undergo as they differentiate towards the various mature hematopoietic lineages. However, it is becoming increasingly clear that changes in chromatin structure do not merely reflect the molecular decision making of transcription factors and the signaling pathways to which they respond. Rather, changes directed at chromatin remodeling help to determine global patterns of gene expression, patterns which can be inherited and enhanced with each cell cycle. Many important hematopoietic regulators have been identified due to their involvement in leukemiaassociated chromosomal translocations. The MOZ gene, situated at chromosomal band 8p1l, is involved in three independent myeloid leukemia translocations. MOZ partner genes disrupted by t(8;16), t(8;22), and inv(8) are, respectively, the CREB binding protein (CBP) at 16p13, P300 at 22q13, and TIF2 (NCoA-2) at 8q13; all three partners are histone acetyltransferases and nuclear receptor coregulators. MOZ is a putative histone acetyltransferase (HAT) and the founding member of the MYST family of HATs, a family that includes proteins involved in cell cycle regulation, chromatin remodeling, and dosage compensation. MOZ's structure suggests that, like CBP/P300 and other members of the HAT superfamily, MOZ participates in protein complexes that modulate both transcriptional activity and chromatin structure. This proposal tests the hypothesis that MOZ is a histone acetyltransferase and transcriptional coregulator that plays an important role during hematopoiesis. Disruption of the MOZ gene by chromosomal translocations is proposed to interfere with critical hematopoietic signaling pathways, disrupt myelopoiesis, and contribute to the development of acute myeloid leukemia. The specific aims of this proposal are to 1) characterize MOZ expression during embryonic development, hematopoiesis, and the cell cycle using northern blotting, western blotting, in situ hybridization, and immunohistochemistry; 2) assess MOZ's coregulatory functions, and its dependence on an intact acetyltransferase activity, using transient and retroviral-mediated stable transfection assays and microinjection studies in hematopoietic and non-hematopoietic cells; and 3) define how disruption of the normal functions of MOZ affects murine embryonic development and hematopoiesis using targeted disruption of the MOZ gene. The long term goal of this project is to understand how MOZ contributes to commitment and terminal differentiation during hematopoiesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THREE LASER BD DIGITAL LSR Principal Investigator & Institution: Schreiber, Hans; Professor; Pathology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Flow cytometry has become an indispensable tool for numerous areas of biological and medical research. Multiple parameters can be measured simultaneously on individual living cells with such a speed that an entire population of cells can be analyzed within seconds to minutes. Rare and unusual events are identified rapidly and expression levels of defined cell-surface or intracellular molecules can be quantified with great ease and precision. The ability to detect such events is particularly critical for the study of cancer and immunological diseases. Uses of the flow cytometry instrument include the monitoring of knockout mice and their reconstitution, analysis of TCR-transgenic mice, the tracking of transferred lymphoid subpopulations, quantification of EGFP-labeled fusion proteins, MHC-tetramer analyses of T cells, identification of variant bacteria, etc. The need for flow cytometric analyses has markedly increased because of an increased awareness of the diverse applications of multiparameter flow cytometry resulting in highly limited availability of the instruments. The PI and the Technical Director have a combined 40-year work experience in analytical cytology. A new 3 Laser BD Digital LSR TM will drastically reduce the current waiting times and provide a cost-efficient highly informative rapid method of analysis to a diverse group of NIH-supported scientists. The Laser BD Digital LSR TM is a state-of-the-art, triple laser, 10 parameter, 8-color analyzer, with a dual thresholding ability ideal for analysis of small particles. The efficiency of the usage of the Laser BD Digital LSR TM will be further increased by placing the unit into the existing Flow Cytometry Facility. Integration of this unit into this facility will guarantee supervision and management by an outstanding, highly experienced Technical Director, Julie Auger, and continued support as part of the institution's Cancer Center Core. Inclusion into an already established system of on-line bookings ensures and documents the maximal and fair usage of the instrument. An already established Internal Advisory Committee will oversee an equitable and appropriate use by a broad multidisciplinary group of scientists while giving priority to NIH supported groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TWO-PHOTO OPTICAL BIOPSY PROBE Principal Investigator & Institution: So, Peter T.; Associate Professor; Mechanical Engineering; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Two-photon microscope is a powerful tool for in vivo imaging of cellular and extracellular matrix structures with sub-micron resolution. Two-photon based non-invasive optical biopsy methods have the potential of being used as an adjunct to excisional biopsy and histopathology. While the utility of twophoton microscopy for biological studies has been clearly demonstrated in areas such as neurobiology and embryology, its clinical potential remains unrealized. The operational complexity, size, imaging speed and cost stand in the way of testing this new technology in a clinical setting. This proposal addresses these difficulties by engineering a compact two-photon optical biopsy probe. A hand-held device will be built to image tissue cellular structures at video rate (> 10 frames/sec) with sub-cellular resolution down to a depth of 150-200 -1. A number of preliminary studies have been completed to

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demonstrate the feasibility of this project. (1) The use of two- photon excitation to image tissue cellular structures and metabolism based on its autofluorescence was demonstrated, Preliminary data indicating this technique's potential to distinguish normal and malignant tissues are included. (2) A prototype video-rate two-photon microscope was constructed. (3) A confocal reflected-light imaging sub-system was incorporated into a two-photon microscope. (4) The distribution of tissue biochemical constituents has been resolved based on their two-photon spectra. (5) The key twophoton photodamage mechanisms were identified, The aim of this proposal is to develop a hand-held two-photon biopsy probe suitable for clinical research. We will study the engineering challenges associated with miniaturizing two-photon technology such as the delivep ultra-short light pulses. It is also critical to avoid tissue photodamage; the maximum perr&sibl.e laser power and dosage levels will be established. We will characterize the performance this device in tissue phantoms, animal models and excised human skin biopsy specimens. We hope that the successful completion of this project will result in a first generation device that will allow the evaluation of two-photon optical biopsy techniques in the clinics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: U GUAM RISE EQUIPMENT SUPPLEMENT FOR R25 GM63682-01 Principal Investigator & Institution: Lobban, Christopher S.; Biology; University of Guam Uog Station Mangilao, Gu 96923 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): The three instruments requested here will significantly enhance the biomedical research climate for students and faculty at the University of Guam. This will immediately serve the RISE goals of student and faculty development, and will add to integration of teaching and research that will motivate more students to complete the baccalaureate degree and go on to graduate school, and more teaching faculty to publish and apply for research grants. The three instruments requested include a low-field nuclear magnetic resonance (NMR) spectrometer, a VersaDoc 1000 Imager, and a differential interference contrast (DIC)/fluorescence microscope to support training of students in modern microscopy. Each of these instruments will serve all our biology and chemistry majors (-60-70 students) through 9 chemistry and 8 biology courses. By using the instruments in different courses, students will develop the ability to apply the techniques to novel situations in their research. The equipment will also be used in faculty research projects, often with students, which will increase output of presentations and publications and contribute preliminary data toward grant applications. The Data from the Imager and microscope will be shared through the new RISE Science LAN. Provision has been made for maintenance of the equipment by the University under the responsibility of the named faculty. NMR is one of the most important and powerful spectroscopic techniques in organic and biochemistry, but is not currently available on Guam. The NMR most suited to our teaching needs, small institution size, and remote location is a refurbished 60 MHz Fourier Transform spectrometer equipped with a permanent magnet and 1H and _C Probes. This system is much more resilient than a superconducting 300 MHz instrument, requires no cryogenics, and can and maintained by the University with available resources. The chemist in charge attended an NSF-sponsored workshop on NMR last year The VersaDoc Imager and associated statistical analyses will allow us to advance the genetics and molecular labs into quantitative analysis. Students will learn to design experiments with precision to accurately estimate population genetic parameters and will be able to implement the types of automated, quantitative measurements they

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will need in biomedical research. With the DIC/FL microscope students will learn to select and set up appropriate optics for biodiversity and cytology studies. The superior views of living biological specimens from DIC optics in the microscope will deepen students' understanding of biological systems and further their contribution to research into the marine biota of Guam. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VECTOR QUANTIZATION FOR IMAGE PATTERN RECOGNITION Principal Investigator & Institution: Soenksen, Dirk G.; Aperio Technologies, Inc. 1430 Vantage Ct, Ste 106 Vista, Ca 92083 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-JAN-2004 Summary: (provided by applicant): This Phase-I SBIR application addresses the increasingly significant challenges faced by pathologists and clinicians in manually inspecting microscope slides. Microscopic inspection suffers from being labor-intensive, subjective, expensive and limited by the need for physical access to the glass slide specimen of interest. The obstacle to automated microscopic inspection has been the inability to efficiently digitize entire microscope specimens at high resolutions. Aperio has developed the ScanScope (R), a novel microscope slide scanner that makes it practical - for the first time - to rapidly create virtual microscope slides at high resolutions. Virtual slides set the stage for automating microscopic inspection using automated pattern recognition. This research aims to adapt and optimize Aperio's existing and novel algorithms for vector quantization (VQ) to the problem of automatic pattern recognition in virtual slides. VQ is a general mathematical technique for encoding bitstreams using a vocabulary. The primary aim is to demonstrate the feasibility of using VQ for pattern recognition in a practical and well-characterized application: automatically finding virtually all micrometastasis clusters in cytology specimens. This proposed research represents a first attempt to automate pattern recognition in virtual slides using VQ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ZEISS DECONVOLUTION

MICROSCOPE

FOR

LIVE

CELL

IMAGING

&

Principal Investigator & Institution: Bar-Sagi, Dafna; Professor & Chair; Molecular Genetics & Microbiol; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: The spatial coordination of biological molecules is of central importance to virtually all aspects of cell physiology. Consequently, high resolution microscopy is now widely recognized as an essential tool to investigate the regulation and dynamics of a broad spectrum of cellular processes including gene expression, intracellular trafficking and cell motility. In this application, we request funds for the purchase of a Zeiss Microscopy Workstation for Live Cell Imaging and Deconvolution which will allow high resolution 3-dimensional imaging of multi-labeled fixed or live samples. The main components of this integrated imaging system include a fully motorized inver6ted microscope (Anxiovert 200 M), a temperature and Co2-controlled chamber (Zeiss Cell Observer), a high definition cooled CCD camera (AxioCam), a nitrogen-pumped dye laser (Photonic Instruments), and a computer loaded with Zeiss Axiovision software for image acquisition and deconvolution analysis. This microscopy workstation will be used primarily by six NIH-funded investigators affiliated with two departments at the State University of New York at Stony Brook: Biochemistry and Molecular Genetics and

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Microbiology. There are no other facilities for live cell imaging and deconvolution microscopy on the Stony Brook campus. Therefore the acquisition of the Zeiss microscopy workstation will provide the only access this group of investigators would have to a powerful imaging technology that will undoubtedly enhance their research objectives. The Zeiss Microscopy Workstation will be housed in a 750 sq. ft. room located in the Department of Molecular Genetics and Microbiology. It will be maintained by a trained technical support person and operated by the individual users. The Principal Investigator will provide scientific oversight and will supervise the training of users. An advisory committee will assist in the development and implementation of guidelines of the shared use of the instrument. It is anticipated that the information gathered through the use of the Zeiss Microscopy Workstation will provide new insights into the mechanisms that control cellular behavior under physiological and pathological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with cytology, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “cytology” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for cytology (hyperlinks lead to article summaries): •

A comparison of cytology with Pap smears taken by a gynecologist and with a selfsampling device. Author(s): Pengsaa P, Sriamporn S, Kritpetcharat O, Kamsa-Ard S, Suwanrungruang K, Noda S, Kakudo K. Source: Asian Pac J Cancer Prev. 2003 April-June; 4(2): 99-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875620

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A perspective on cytology of lung cancer. Author(s): Bhatia A, Singh N, Arora VK. Source: Indian J Chest Dis Allied Sci. 2004 April-June; 46(2): 81-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15072321

3

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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•

A prospective comparison of digital image analysis and routine cytology for the identification of malignancy in biliary tract strictures. Author(s): Baron TH, Harewood GC, Rumalla A, Pochron NL, Stadheim LM, Gores GJ, Therneau TM, De Groen PC, Sebo TJ, Salomao DR, Kipp BR. Source: Clin Gastroenterol Hepatol. 2004 March; 2(3): 214-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017605

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A prospective study of the use of fine-needle aspiration cytology and core biopsy in the diagnosis of breast cancer. Author(s): Dennison G, Anand R, Makar SH, Pain JA. Source: The Breast Journal. 2003 November-December; 9(6): 491-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616944

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Abnormal cervical cytology: new names, familiar smears. Author(s): Carulli DT. Source: Journal of the American Academy of Nurse Practitioners. 2003 October; 15(10): 444-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606133

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Accuracy of fine-needle aspiration cytology in patients with radiation-induced thyroid neoplasms (Br J Surg 2003; 90: 755-758). Author(s): Chintamani, Bhatnagar D. Source: The British Journal of Surgery. 2003 November; 90(11): 1452. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598434

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ACOG practice bulletin. Cervical Cytology screening. Number 45, August 2003. Author(s): American College of Obstetricians and Gynecologists. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 November; 83(2): 237-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631934

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ACOG Practice Bulletin: clinical management guidelines for obstetriciangynecologists. Number 45, August 2003. Cervical cytology screening (replaces committee opinion 152, March 1995). Author(s): ACOG Committee on Practice Bulletins. Source: Obstetrics and Gynecology. 2003 August; 102(2): 417-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907124

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ACOG releases guidelines on cervical cytology screening. Author(s): Ressel GW; American College of Obstetricians and Gynecologists. Source: American Family Physician. 2003 November 15; 68(10): 2081, 2084. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655818

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Adenoid cystic carcinoma: a pitfall in aspiration cytology of the thyroid. Author(s): Idowu MO, Reiter ER, Powers CN. Source: American Journal of Clinical Pathology. 2004 April; 121(4): 551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080307

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Alterations in conjunctival cytology and tear film dysfunction in patients with betathalassemia. Author(s): Gartaganis SP, Georgakopoulos CD, Exarchou A, Mela EK, Psachoulia C, Eliopoulou MI, Kourakli A, Gotsis SS, Tripathi RC. Source: Cornea. 2003 October; 22(7): 591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508254

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Alternative, cost-effective fungus-staining method for control slides in cytology and histopathology. Author(s): da Silva VD. Source: Acta Cytol. 2003 November-December; 47(6): 1043-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674076

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An alternate model of thyroid cytology: practical not perfect. Author(s): Holbrook MR, Kendall CH, Shaw PA. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828720

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An analysis of 84244 patients from the British Columbia cytology-colposcopy program. Author(s): Benedet JL, Matisic JP, Bertrand MA. Source: Gynecologic Oncology. 2004 January; 92(1): 127-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751148

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Analysis of limbal stem cell deficiency by corneal impression cytology. Author(s): Donisi PM, Rama P, Fasolo A, Ponzin D. Source: Cornea. 2003 August; 22(6): 533-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883346

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Analysis of urine cytology at a community hospital. Author(s): Mansoor I. Source: J Ayub Med Coll Abbottabad. 2003 April-June; 15(2): 20-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552242

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Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation. Author(s): Friedlander MA, Stier E, Lin O. Source: Cancer. 2004 February 25; 102(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968414

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Applicability of liquid-based cytology to the assessment of DNA content in cervical lesions using static cytometry. Author(s): Shirata NK, Longatto Filho A, Roteli-Martins C, Espoladore LM, Pittoli JE, Syrjanen K. Source: Anal Quant Cytol Histol. 2003 August; 25(4): 210-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12961827

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Aspiration cytology of ameloblastic fibroma: a diagnostic challenge. Author(s): Kumar N, Jain S. Source: Diagnostic Cytopathology. 2003 August; 29(2): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889050

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Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland. Author(s): Moreira AL, Waisman J, Cangiarella JF. Source: Acta Cytol. 2004 March-April; 48(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085743

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Basal cell adenocarcinoma of the salivary gland: report of a case with morphology on fine needle aspiration cytology. Author(s): Tse GM, To EW, Yuen EH, Chen M. Source: Acta Cytol. 2001 September-October; 45(5): 775-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575660

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Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10year cohort analysis. Author(s): Sherman ME, Lorincz AT, Scott DR, Wacholder S, Castle PE, Glass AG, Mielzynska-Lohnas I, Rush BB, Schiffman M. Source: Journal of the National Cancer Institute. 2003 January 1; 95(1): 46-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509400

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Benign stromal fragments in metastases of squamous cell carcinoma in cytology--a report of two cases. Author(s): Deshpande AH, Munshi MM. Source: Indian J Pathol Microbiol. 2003 July; 46(3): 440-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025296

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Bethesda 2001. Impact on the reporting of gynecologic cytology. Author(s): Chhieng DC, Roberson J, Gidley J, Eltoum I. Source: Acta Cytol. 2004 May-June; 48(3): 355-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192951

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Biopsy correlates of abnormal cervical cytology classified using the Bethesda system. Author(s): Massad LS, Collins YC, Meyer PM. Source: Gynecologic Oncology. 2001 September; 82(3): 516-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520149

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Bladder-washing cytology of metastatic ovarian granulosa cell tumor. Author(s): Vodovnik A. Source: Diagnostic Cytopathology. 2002 June; 26(6): 387-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112830

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Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid. Author(s): Wrensch MR, Petrakis NL, Miike R, King EB, Chew K, Neuhaus J, Lee MM, Rhys M. Source: Journal of the National Cancer Institute. 2001 December 5; 93(23): 1791-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734595

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Breast cancer risk prediction: should nipple aspiration fluid cytology be incorporated into clinical practice? Author(s): Fabian CJ, Kimler BF. Source: Journal of the National Cancer Institute. 2001 December 5; 93(23): 1762-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734584

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Breast carcinoma with neuroendocrine differentiation: diagnosis of a case by fine needle aspiration cytology and immunocytochemistry. Author(s): Das DK, Sheikh ZA. Source: Acta Cytol. 2004 March-April; 48(2): 292-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085773

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Breast cell proliferation in postmenopausal women during HRT evaluated through fine needle aspiration cytology. Author(s): Conner P, Soderqvist G, Skoog L, Graser T, Walter F, Tani E, Carlstrom K, von Schoultz B. Source: Breast Cancer Research and Treatment. 2003 March; 78(2): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725416

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Breast metastasis of asymptomatic lung carcinoma diagnosed by fine needle aspiration cytology. Author(s): Sah SP, Rani S, De U. Source: Acta Cytol. 2002 November-December; 46(6): 1166-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462101

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Broad ligament recurrence of ovarian granulosa cell tumour detected by touch imprint cytology. Author(s): Tamiolakis D, Venizclos J, Karamanidis D, Prassopoulos P, Papadopoulos N. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 226-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873320

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Bronchial cytology in pleural mesothelioma. A report of 3 positive cases, including 1 diagnosed initially on bronchial brushings. Author(s): DellaGiustina D, Falconieri G, Bonifacio-Gori D, Zanconati F, DiBonito L, Pizzolitto S. Source: Acta Cytol. 2003 November-December; 47(6): 1017-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674071

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Brush cytology in malignant biliary obstruction. Author(s): Singh V, Bhasin S, Nain CK, Gupta SK, Singh G, Bose SM. Source: Indian J Pathol Microbiol. 2003 April; 46(2): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022908

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Brush cytology of colorectal malignancies. Author(s): Geramizadeh B, Hooshmand F, Kumar PV. Source: Acta Cytol. 2003 May-June; 47(3): 431-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789927

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Brush cytology of gastric malignancies. Author(s): Geramizadeh B, Shafiee A, Saberfirruzi M, Kumar PK, Shaheem A. Source: Acta Cytol. 2002 July-August; 46(4): 693-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12146033

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Brush cytology of the biliary tract: retrospective study of 278 cases with histopathologic correlation. Author(s): Govil H, Reddy V, Kluskens L, Treaba D, Massarani-Wafai R, Selvaggi S, Gattuso P. Source: Diagnostic Cytopathology. 2002 May; 26(5): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992366

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Brushing, sputum, bronchoalveolar lavage and imprint cytology in the Churg-Strauss syndrome. Author(s): Babjakova L, Jurkovic I, Boor A, Krajcar R, Zak V, Toth S. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 166-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828729

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BTA TRAK urine test increases the efficacy of cytology in the diagnosis of low-grade transitional cell carcinoma of the bladder. Author(s): Gibanel R, Ribal MJ, Filella X, Ballesta AM, Molina R, Alcaraz A, Alcover JB. Source: Anticancer Res. 2002 March-April; 22(2B): 1157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12168917

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Burkitt-type lymphoma of the breast: diagnosis by fine-needle aspiration cytology. Author(s): Das DK, Sheikh ZA, Jassar AK, Jarallah MA. Source: Diagnostic Cytopathology. 2002 July; 27(1): 60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112818

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Can human papillomavirus DNA testing substitute for cytology in the detection of high-grade cervical lesions? Author(s): Lee KJ, Lee JK, Saw HS. Source: Archives of Pathology & Laboratory Medicine. 2004 March; 128(3): 298-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987159

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Case of adrenal lymphangioma with atypical lymphocytes in aspirate cytology. Author(s): Satou T, Uesugi T, Nakai Y, Hayashi Y, Imano M, Hashimoto S. Source: Diagnostic Cytopathology. 2003 August; 29(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889047

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Cervical cancer screening: liquid based cytology is successful. Author(s): Whitley MW. Source: Bmj (Clinical Research Ed.). 2003 July 19; 327(7407): 161-2; Author Reply 162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869464

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Cervical cancer screening: liquid based cytology may be preferred option for UK screening programme. Author(s): Ind T. Source: Bmj (Clinical Research Ed.). 2003 July 19; 327(7407): 161; Author Reply 162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869465

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Cervical cytology in an urban population in Lagos, Nigeria. Author(s): Anorlu RI, Abdul-Kareem FB, Abudu OO, Oyekan TO. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850863

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Cervical cytology screening practices among obstetrician-gynecologists. Author(s): Noller KL, Bettes B, Zinberg S, Schulkin J. Source: Obstetrics and Gynecology. 2003 August; 102(2): 259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907097

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Cervical cytology: an audit in a Singapore teaching hospital. Author(s): Thamboo TP, Salto-Tellez M, Tan KB, Nilsson B, Rajwanshi A. Source: Singapore Med J. 2003 May; 44(5): 256-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13677362

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Combined radiology and cytology in the diagnosis of bone lesions--a review of 399 cases. Author(s): Soderlund V. Source: Acta Orthop Scand Suppl. 2004 April; 75(311): 51-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188665

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Comparison of cytology and nuclear matrix protein 22 (NMP 22) for the detection and follow-up of bladder-cancer. Author(s): Lahme S, Bichler KH, Feil G, Zumbragel A, Gotz T. Source: Advances in Experimental Medicine and Biology. 2003; 539(Pt A): 111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088900

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Comparison of manual and automated methods of liquid-based cytology. A morphologic study. Author(s): Alves VA, Bibbo M, Schmitt FC, Milanezi F, Longatto Filho A. Source: Acta Cytol. 2004 March-April; 48(2): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085750

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Comparison of stereotactic fine needle aspiration cytology and core needle biopsy in 522 non-palpable breast lesions. Author(s): Leifland K, Lagerstedt U, Svane G. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2003 July; 44(4): 387-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846688

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Correlation of fine needle aspiration cytology and its histopathology in diagnosis of breast lumps. Author(s): Khatun H, Tareak-Al-Nasir, Enam S, Hussain M, Begum M. Source: Bangladesh Med Res Counc Bull. 2002 August; 28(2): 77-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825765

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Cross-sectional study of patient- and physician-collected cervical cytology and human papillomavirus. Author(s): Garcia F, Barker B, Santos C, Brown EM, Nuno T, Giuliano A, Davis J. Source: Obstetrics and Gynecology. 2003 August; 102(2): 266-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907098

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CT-scan, MRI and image-guided FNA cytology of incidental adrenal masses. Author(s): Lumachi F, Borsato S, Tregnaghi A, Basso SM, Marchesi P, Ciarleglio F, Fassina A, Favia G. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2003 October; 29(8): 689-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511619

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Cysticercosis diagnosed by fine needle aspiration cytology. Author(s): Agrawal KC, Mishra DP, Das PK. Source: Acta Cytol. 2004 May-June; 48(3): 471-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192979

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Cytologic and histologic review of atypical glandular cells (AGC) detected during cervical cytology screening. Author(s): Jeng CJ, Liang HS, Wang TY, Shen J, Yang YC, Tzeng CR. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 July-August; 13(4): 518-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911731

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Cytology and lineage of NG2-positive glia. Author(s): Berry M, Hubbard P, Butt AM. Source: Journal of Neurocytology. 2002 July-August; 31(6-7): 457-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501216

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Cytology in Barrett's esophagus. Author(s): Falk GW. Source: Gastrointest Endosc Clin N Am. 2003 April; 13(2): 335-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916664

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Cytology of human ovarian surface epithelial brushings. Author(s): Nicosia SV, Wilbanks GD, Saunders B, Mayer J, Cardosi RJ, Kruk PA, Cheng J, Bai W, Coppola D, Fiorica J. Source: Cancer. 2004 February 25; 102(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968412

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Cytology of subependymoma. Author(s): Raisanen J, Burns DK, White CL. Source: Acta Cytol. 2003 May-June; 47(3): 518-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789945

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Dermal analogue tumor of the salivary gland diagnosed by fine needle aspiration cytology. A case report. Author(s): Vera-Alvarez J, Marigil-Gomez M, Garcia-Prats MD, Abascal-Agorreta M, Lacasa-Laliena M, Lopez-Lopez JI. Source: Acta Cytol. 2004 January-February; 48(1): 78-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969186

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Detection of bladder tumours: role of cytology, morphology-based assays, biochemical and molecular markers. Author(s): Eissa S, Kassim S, El-Ahmady O. Source: Current Opinion in Obstetrics & Gynecology. 2003 October; 15(5): 395-403. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501243

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Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study. Author(s): Wensveen C, Kagie M, Veldhuizen R, De Groot C, Denny L, Zwinderman K, Trimbos B. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2003 September; 82(9): 883-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911453

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Detection of disseminated tumor cells in neuroblastoma: 3 log improvement in sensitivity by automatic immunofluorescence plus FISH (AIPF) analysis compared with classical bone marrow cytology. Author(s): Mehes G, Luegmayr A, Kornmuller R, Ambros IM, Ladenstein R, Gadner H, Ambros PF. Source: American Journal of Pathology. 2003 August; 163(2): 393-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875961

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Detection of regional melanoma metastases by ultrasound B-scan, cytology or tyrosinase RT-PCR of fine-needle aspirates. Author(s): Voit C, Schoengen A, Schwurzer M, Weber L, Mayer T, Proebstle TM. Source: British Journal of Cancer. 1999 July; 80(10): 1672-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408417

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Detection of residual disease by cytology in patients with cervical intraepithelial neoplasia III post-large loop excision of the transformation zone. Author(s): Tangtrakul S, Linasmita V, Israngura N, Srisupundit S, Bullangpoti S, Wilailak S. Source: The Journal of Obstetrics and Gynaecology Research. 2002 April; 28(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12078976

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Diagnosis of chondroid syringoma by fine needle aspiration cytology. Author(s): Kumar S, Ghotekar LH, Thappa DM, Smile R. Source: Acta Cytol. 2003 May-June; 47(3): 522-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789947

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Diagnosis of hepatocellular carcinoma by fine needle aspiration cytology. Cellular features. Author(s): Soyuer I, Ekinci C, Kaya M, Genc Y, Bahar K. Source: Acta Cytol. 2003 July-August; 47(4): 581-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920750

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Diagnosis of rare malignant tumours of the breast by FNA cytology--a report of 3 cases. Author(s): Sheshappanavar VG, Raghupathi MC. Source: Indian J Pathol Microbiol. 2003 April; 46(2): 248-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022930

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Diagnosis of thyroid metastasis in cancer patients with thyroid mass by fine needle aspiration cytology and ultrasonography. Author(s): Lin SY, Sheu WH, Chang MC, Tang KT, Lee TI, Lin HD. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 March; 65(3): 101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051452

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Diagnostic accuracy of fine-needle aspiration cytology and frozen section in primary parotid carcinoma. Author(s): Zbaren P, Nuyens M, Loosli H, Stauffer E. Source: Cancer. 2004 May 1; 100(9): 1876-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15112268

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Diagnostic approach of effusion cytology using computerized image analysis. Author(s): Athanassiadou P, Kavantzas N, Davaris P, Gonidi M, Liossi A, Nakopoulou L, Petrakakou E, Athanassiades P. Source: J Exp Clin Cancer Res. 2002 March; 21(1): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12071529

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Diagnostic pitfalls of peritoneal washing cytology and the role of cell blocks in their diagnosis. Author(s): Selvaggi SM. Source: Diagnostic Cytopathology. 2003 June; 28(6): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768641

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Diagnostic use of mean nuclear area and nuclear DNA content in preoperative breast cancer cytology. Author(s): Sarker SK. Source: Anal Quant Cytol Histol. 2003 April; 25(2): 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746976

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Diagnostic utility and limitations of electron microscopy in effusion fluid cytology smears. Author(s): Ng WK, Yau BW, Ma L. Source: Diagnostic Cytopathology. 2003 July; 29(1): 46-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827717

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Diagnostic value of cytology and colposcopy for squamous and glandular cervical intraepithelial lesions. Author(s): Pajtler M, Audy-Jurkovic S, Ovanin-Rakic A, Makarovic Z, Milojkovic M, Ljubojevic N. Source: Coll Antropol. 2003 June; 27(1): 239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974152

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Diagnostic value of needle aspiration cytology in the assessment of palpable axillary lymph nodes. A study of 336 cases. Author(s): Gupta RK, Naran S, Lallu S, Fauck R. Source: Acta Cytol. 2003 July-August; 47(4): 550-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920745

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Diagnostic value of transbronchial needle aspiration by Wang 22-gauge cytology needle in intrathoracic lymphadenopathy. Author(s): Cetinkaya E, Yildiz P, Altin S, Yilmaz V. Source: Chest. 2004 February; 125(2): 527-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769734

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Does imprint cytology of brain tumours improve intraoperative diagnoses? Author(s): Brommeland T, Lindal S, Straume B, Dahl IL, Hennig R. Source: Acta Neurologica Scandinavica. 2003 September; 108(3): 153-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911456

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Dynamic MRI and fine needle aspiration cytology in the evaluation of soft tissue lesions. Author(s): Einarsdottir H, Soderlund V, Skoog L, Bauer HC. Source: Skeletal Radiology. 2003 December; 32(12): 695-700. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830327

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Early diagnosis of kidney transplant rejection and cyclosporin nephrotoxicity by urine cytology. Author(s): Kyo M, Gudat F, Dalquen P, Huser B, Thiel G, Fujimoto N, Ichikawa Y, Fukunishi T, Nagano S, Mihatsch MJ. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621720

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Efficacy of bronchial wash cytology and its correlation with biopsy in lung tumours. Author(s): Ahmad M, Afzal S, Saeed W, Mubarik A, Saleem N, Khan SA, Rafi S. Source: J Pak Med Assoc. 2004 January; 54(1): 13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15058635

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Efficacy of lodoxamide eye drops on tear fluid cytology of patients with vernal conjunctivitis. Author(s): Oguz H, Bitiren M, Aslan OS, Ozardali I. Source: Acta Medica Okayama. 1999 June; 53(3): 123-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410789

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Efficiency of the hybrid capture 2 HPV DNA test in cervical cancer screening. A study by the French Society of Clinical Cytology. Author(s): de Cremoux P, Coste J, Sastre-Garau X, Thioux M, Bouillac C, Labbe S, Cartier I, Ziol M, Dosda A, Le Gales C, Molinie V, Vacher-Lavenu MC, Cochand-Priollet B, Vielh P, Magdelenat H; French Society of Clinical Cytology Study Group. Source: American Journal of Clinical Pathology. 2003 October; 120(4): 492-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560561

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Effusion cytology in ovarian cancer: new molecular methods as aids to diagnosis and prognosis. Author(s): Davidson B, Risberg B, Reich R, Berner A. Source: Clin Lab Med. 2003 September; 23(3): 729-54, Viii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560537

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Effusion cytology of pleural mesothelioma, epithelial type, with extreme cytoplasmic vacuolization. Author(s): Akin MR, Nguyen GK. Source: Acta Cytol. 2004 May-June; 48(3): 469-71. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192978

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Endocervical curettage. Does it contribute to the management of patients with abnormal cervical cytology? Author(s): Irvin W, Flora S, Andersen W, Stoler M, Taylor P, Rice L. Source: J Reprod Med. 2004 January; 49(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976787

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Endometrial cytology in early diagnosis of adenocarcinoma arising from adenomyosis uteri. Author(s): Kawana K, Shirai T, Jimbo H, Yoshida M, Takahashi M, Shiromizu K, Nishida K, Sano Y, Kawana K, Jimbo H. Source: Acta Cytol. 2002 May-June; 46(3): 612-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040664

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Endoscopic ultrasound-guided fine needle aspiration cytology of solid liver lesions: a large single-center experience. Author(s): DeWitt J, LeBlanc J, McHenry L, Ciaccia D, Imperiale T, Chappo J, Cramer H, McGreevy K, Chriswell M, Sherman S. Source: The American Journal of Gastroenterology. 2003 September; 98(9): 1976-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499774

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Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solidpseudopapillary tumor of the pancreas: a rare neoplasm of elusive origin but characteristic cytomorphologic features. Author(s): Bardales RH, Centeno B, Mallery JS, Lai R, Pochapin M, Guiter G, Stanley MW. Source: American Journal of Clinical Pathology. 2004 May; 121(5): 654-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15151205

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EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology. Author(s): Fritscher-Ravens A, Broering DC, Knoefel WT, Rogiers X, Swain P, Thonke F, Bobrowski C, Topalidis T, Soehendra N. Source: The American Journal of Gastroenterology. 2004 January; 99(1): 45-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687140

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Evaluation of a centrifuge method and thin-layer preparation in urine cytology. Author(s): Zardawi IM, Duncan J. Source: Acta Cytol. 2003 November-December; 47(6): 1038-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674075

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Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma. Author(s): Fujimoto T, Zhang B, Minami S, Wang X, Takahashi Y, Mai M. Source: Oncology. 2002; 62(3): 201-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065866

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Evaluation of liquid-based cytology in cervical screening of high-risk populations: a split study of colposcopy and genito-urinary medicine populations. Author(s): Ring M, Bolger N, O'Donnell M, Malkin A, Bermingham N, Akpan E, Mulcahy F, Turner MJ, Griffin M, O'Leary JJ. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2002 June; 13(3): 152-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060077

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Evidence and thoughts about thyroid nodules that grow after they have been identified as benign by aspiration cytology. Author(s): Blum M, Hussain MA. Source: Thyroid : Official Journal of the American Thyroid Association. 2003 July; 13(7): 637-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964968

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Examination for the Certificate in Advanced Practice in Cervical Cytology--the first year's experience. Author(s): Smith PA, Hewer EM. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828716

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Exfoliative cytology of the oral mucosa in type II diabetic patients: morphology and cytomorphometry. Author(s): Alberti S, Spadella CT, Francischone TR, Assis GF, Cestari TM, Taveira LA. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2003 October; 32(9): 538-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969228

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Expressions of human telomerase mRNA component (hTERC) and telomerase reverse transcriptase (hTERT) mRNA in effusion cytology. Author(s): Hiroi S, Nakanishi K, Kawai T. Source: Diagnostic Cytopathology. 2003 October; 29(4): 212-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506674

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External quality assessment (EQA) in gynaecological cytology: radical rethinking required? Author(s): Slater DN. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 1999 June; 10(3): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10390063

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External quality assurance for cervical cytology in developing countries. Experience in Peru and Nicaragua. Author(s): Salvetto M, Sandiford P. Source: Acta Cytol. 2004 January-February; 48(1): 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969177

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Fine needle aspiration cytology findings of cystic hypersecretory ductal carcinoma of the breast: a reappraisal. Author(s): Ng WK, Yip WW. Source: Acta Cytol. 2003 May-June; 47(3): 513-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789942

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Fine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitre. Author(s): Slowinska-Klencka D, Klencki M, Sporny S, Lewinski A. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873316

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Fine needle aspiration cytology of a primary amyloid tumor of the breast. Author(s): Zardawi IM, Catterall N, Clark DA. Source: Acta Cytol. 2004 March-April; 48(2): 286-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085770

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Fine needle aspiration cytology of Burkitt's lymphoma presenting as a breast mass. Author(s): Geramizadeh B, Kaboli R, Vasei M. Source: Acta Cytol. 2004 March-April; 48(2): 285-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085769

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Fine needle aspiration cytology of clear cell sarcoma of the kidney with spindle cell pattern. Author(s): Iyer VK, Kapila K, Verma K. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 160-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828728

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Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases. Author(s): Jimenez-Heffernan JA, Vicandi B, Lopez-Ferrer P, Gonzalez-Peramato P, Perez-Campos A, Viguer JM. Source: Acta Cytol. 2004 May-June; 48(3): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192942

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Fine needle aspiration cytology of fibrous histiocytomas of the lung. Author(s): Hoshi R, Satoh Y, Tsuzuku M, Horai T, Ishikawa Y. Source: Acta Cytol. 2004 March-April; 48(2): 290-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085772

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Fine needle aspiration cytology of follicular variant of papillary carcinoma of thyroid. Author(s): Powari M, Dey P, Saikia UN. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 212-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873315

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Fine needle aspiration cytology of granulomatous mastitis. Author(s): Tse GM, Poon CS, Law BK, Pang LM, Chu WC, Ma TK. Source: Journal of Clinical Pathology. 2003 July; 56(7): 519-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835297

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Fine needle aspiration cytology of mammary hamartoma: a review of nine cases with histological correlation. Author(s): Gomez-Aracil V, Mayayo E, Azua J, Mayayo R, Azua-Romeo J, Arraiza A. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873312

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Fine needle aspiration cytology of primary epithelioid sarcoma. A report of 2 cases. Author(s): Kitagawa Y, Ito H, Sawaizumi T, Matsubara M, Yokoyama M, Naito Z, Maeda S, Sugisaki Y. Source: Acta Cytol. 2004 May-June; 48(3): 391-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192957

Studies

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Fine needle aspiration cytology of pulmonary rheumatoid nodule. Author(s): Gonzalez-Peramato P, Jimenez-Heffernan JA, Bayo A, Vicandi B. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 227-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873321

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Fine needle aspiration cytology of small cell variant of anaplastic large cell lymphoma. A case report. Author(s): Kim SE, Kim SH, Lim BJ, Hong SW, Yang WI. Source: Acta Cytol. 2004 March-April; 48(2): 254-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085763

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Fine-needle aspiration cytology of giant cell tumor of tendon sheath. Author(s): Iyer VK, Kapila K, Verma K. Source: Diagnostic Cytopathology. 2003 August; 29(2): 105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889051

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Fine-needle aspiration cytology of intraabdominal extralobar pulmonary sequestration: a case report. Author(s): Rajendiran S, Kapoor V, Schoedel K. Source: Diagnostic Cytopathology. 2003 July; 29(1): 24-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827711

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Fine-needle aspiration cytology of mucinous tumors of the pancreas. Author(s): Recine M, Kaw M, Evans DB, Krishnamurthy S. Source: Cancer. 2004 April 25; 102(2): 92-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15098253

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Fine-needle aspiration cytology of thyroid nodules: how useful is it? Author(s): Morgan JL, Serpell JW, Cheng MS. Source: Anz Journal of Surgery. 2003 July; 73(7): 480-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864820

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Fine-needle aspiration cytology: true histiocytic lymphoma/histiocytic sarcoma. Author(s): Miliauskas JR. Source: Diagnostic Cytopathology. 2003 October; 29(4): 233-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506679

76

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Flow cytometry in conjunctival impression cytology: a new tool for exploring ocular surface pathologies. Author(s): Brignole-Baudouin F, Ott AC, Warnet JM, Baudouin C. Source: Experimental Eye Research. 2004 March; 78(3): 473-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15106926

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Fractal dimensions of breast lesions on cytology smears. Author(s): Dey P, Mohanty SK. Source: Diagnostic Cytopathology. 2003 August; 29(2): 85-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889046

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Galactography and exfoliative cytology in women with abnormal nipple discharge. Author(s): Dinkel HP, Gassel AM, Muller T, Lourens S, Rominger M, Tschammler A. Source: Obstetrics and Gynecology. 2001 April; 97(4): 625-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275040

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Gastric cancer cell detection in peritoneal washing: cytology versus RT-PCR for CEA transcripts. Author(s): To EM, Chan WY, Chow C, Ng EK, Chung SC. Source: Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B. 2003 June; 12(2): 88-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766613

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Gastric carcinoma detected by cervical cytology. Author(s): Franchi R, Signaroldi A, Croce P, Dede A, Paties CT, Sbalzarini G. Source: Anti-Cancer Drugs. 2000 September; 11(8): 645-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081457

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Gastric tuberculosis. Endoscopic cytology as a diagnostic tool. Author(s): Jain S, Kumar N, Jain SK. Source: Acta Cytol. 2000 November-December; 44(6): 987-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11127757

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Gastric zygomycosis diagnosed by brushing cytology. Author(s): Pickeral JJ 3rd, Silverman JF, Sturgis CD. Source: Diagnostic Cytopathology. 2000 July; 23(1): 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907934

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Gastrointestinal tract cytology: advancing horizons. Author(s): Jhala N, Jhala D. Source: Advances in Anatomic Pathology. 2003 September; 10(5): 261-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973048

Studies

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Gender, clinical findings, and serum thyrotropin measurements in the prediction of thyroid neoplasia in 1005 patients presenting with thyroid enlargement and investigated by fine-needle aspiration cytology. Author(s): Kumar H, Daykin J, Holder R, Watkinson JC, Sheppard MC, Franklyn JA. Source: Thyroid : Official Journal of the American Thyroid Association. 1999 November; 9(11): 1105-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10595459

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Genotyping of human papillomavirus in liquid cytology cervical specimens by the PGMY line blot assay and the SPF(10) line probe assay. Author(s): van Doorn LJ, Quint W, Kleter B, Molijn A, Colau B, Martin MT, Kravang-In, Torrez-Martinez N, Peyton CL, Wheeler CM. Source: Journal of Clinical Microbiology. 2002 March; 40(3): 979-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11880426

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Gingival fine needle aspiration cytology in acute leukemia. Author(s): Abdullah BH, Yahya HI, Kummoona RK, Hilmi FA, Mirza KB. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2002 January; 31(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896823

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Good practice in head and neck fine needle aspiration cytology as assessed by CUSUM. Author(s): Robinson IA, Blackham RB, Cozens NJ, Sharp J. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2002 December; 13(6): 335-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485168

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Grading follicular lymphoma. The Achilles heel of diagnosis by cytology. Author(s): Young NA, Ehya H. Source: Acta Cytol. 2004 March-April; 48(2): 117-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085739

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Granular cell ameloblastoma of the jaw. A report of two cases with fine needle aspiration cytology. Author(s): Deshpande A, Umap P, Munshi M. Source: Acta Cytol. 2000 January-February; 44(1): 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667166

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Granulomatous mammary disease: ten years' experience with fine needle aspiration cytology. Author(s): Elsiddig KE, Khalil EA, Elhag IA, Elsafi ME, Suleiman GM, Elkhidir IM, Hussein AM, El-Hassan AM. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2003 April; 7(4): 3659. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729342

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Gynecologic cytology turnaround time. A College of American Pathologists Q-Probes Study of 371 laboratories. Author(s): Jones BA, Valenstein PN, Steindel SJ. Source: Archives of Pathology & Laboratory Medicine. 1999 August; 123(8): 682-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10420223

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Have we resolved how to triage equivocal cervical cytology? Author(s): Solomon D, Schiffman M. Source: Journal of the National Cancer Institute. 2004 February 18; 96(4): 250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970266

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Hemophagocytic histiocytosis diagnosed by fine needle aspiration cytology of the spleen. A case report. Author(s): Zeppa P, Vetrani A, Ciancia G, Cuccuru A, Palombini L. Source: Acta Cytol. 2004 May-June; 48(3): 415-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192962

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Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings. Author(s): Mori K, Aoyagi K, Ueda T, Danjoh I, Tsubosa Y, Yanagihara K, Matsuno Y, Sasako M, Sakamoto H, Mafune K, Kaminishi M, Yoshida T, Terada M, Sasaki H. Source: Biochemical and Biophysical Research Communications. 2004 January 23; 313(4): 931-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706632

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Histologic findings from the cervix among older women with abnormal cervical cytology. Author(s): Massad LS, Behbakht K, Collins YC, Cejtin HE. Source: Gynecologic Oncology. 2003 March; 88(3): 340-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648584

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Histology and fine-needle aspiration cytology of malignant thyroid neoplasms. Author(s): Fadda G, LiVolsi VA. Source: Rays. 2000 April-June; 25(2): 139-50. Review. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11370533

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Histopathologic correlation of atypical parakeratosis diagnosed on cervicovaginal cytology. Author(s): Abramovich CM, Wasman JK, Siekkinen P, Abdul-Karim FW. Source: Acta Cytol. 2003 May-June; 47(3): 405-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789922

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How can the uptake of cervical cytology screening be improved? Author(s): Perry MA. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2001 November 28-December 4; 16(11): 33-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11974848

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How do we decide at what age and at what frequency to screen for cancer of the cervix by cervical cytology? Author(s): Miller AB. Source: International Journal of Cancer. Journal International Du Cancer. 2001 December 15; 94(6): 889-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745494

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How important is urinary cytology in the diagnosis of urological malignancies? Author(s): Nabi G, Greene DR, O'Donnell M. Source: European Urology. 2003 June; 43(6): 632-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767364

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How reliable is conventional urinary cytology in post-transplant patients? Author(s): Reichelt O, Wunderlich H, Neiser G, Schubert J. Source: Urologia Internationalis. 2003; 71(2): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890956

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How valuable is ascitic cytology in the detection and management of malignancy? Author(s): Karoo RO, Lloyd TD, Garcea G, Redway HD, Robertson GS. Source: Postgraduate Medical Journal. 2003 May; 79(931): 292-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782778

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HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears. Author(s): Zielinski GD, Snijders PJ, Rozendaal L, Voorhorst FJ, van der Linden HC, Runsink AP, de Schipper FA, Meijer CJ. Source: British Journal of Cancer. 2001 August 3; 85(3): 398-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487272

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Human epithelium from conjunctival impression cytology expresses MUC7 mucin gene. Author(s): Corrales RM, Calonge M, Herreras JM, Saez V, Chaves FJ. Source: Cornea. 2003 October; 22(7): 665-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508262

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Human papillomavirus detection: verification with cervical cytology. Author(s): Matthews-Greer J, Rivette D, Reyes R, Vanderloos CF, Turbat-Herrera EA. Source: Clin Lab Sci. 2004 Winter; 17(1): 8-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011974

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Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs. Author(s): Lorincz AT, Richart RM. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 959-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873167

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Human papillomavirus infection and abnormal cytology of the anus in HIV-infected and uninfected adolescents. Author(s): Moscicki AB, Durako SJ, Houser J, Ma Y, Murphy DA, Darragh TM, Farhat S, Wilson CM. Source: Aids (London, England). 2003 February 14; 17(3): 311-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556684

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Human papillomavirus reporting: impact on Bethesda cytology reports. Author(s): Raab SS. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 969-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873168

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Hybrid capture as a means of detecting human papillomavirus DNA from liquidbased cytology specimens: a preliminary evaluation. Author(s): Callaghan J, Karim S, Mortlock S, Wintert M, Woodward N. Source: British Journal of Biomedical Science. 2001; 58(3): 184-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575742

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Hydatid cyst in soft tissues mimicking malignant tumors. Diagnosis by fine needle aspiration cytology. Author(s): Saenz-Santamaria J, Catalina-Fernandez I, Fernandez de Mera JJ. Source: Acta Cytol. 2003 May-June; 47(3): 337-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789911

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Hysterectomy for abnormal cervical cytology following treatment for cervical intraepithelial neoplasia. Author(s): Manivasagam R, Flynn PM, Bolger BS. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2004 January; 24(1): 72-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675987

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Identification of fibroblast growth factor receptor 3 mutations in urine sediment DNA samples complements cytology in bladder tumor detection. Author(s): Rieger-Christ KM, Mourtzinos A, Lee PJ, Zagha RM, Cain J, Silverman M, Libertino JA, Summerhayes IC. Source: Cancer. 2003 August 15; 98(4): 737-44. Erratum In: Cancer. 2003 November 1; 98(9): 2000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12910517

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Immunocytochemical analysis of fine needle aspiration cytology to improve surgical strategy in thyroid neoplasms. Author(s): Pisani T, Vecchione A, Giovagnoli MR. Source: Acta Cytol. 2003 May-June; 47(3): 520-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789946

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Immunostaining of cytology smears: a comparative study to identify the most suitable method of smear preparation and fixation with reference to commonly used immunomarkers. Author(s): Shidham VB, Chang CC, Rao RN, Komorowski R, Chivukula M. Source: Diagnostic Cytopathology. 2003 October; 29(4): 217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506675

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Impact of liquid-based gynecologic cytology on an HIV-positive population. Author(s): Swierczynski SL, Lewis-Chambers S, Anderson JR, Keller JM, Hinkle DA, Ali SZ. Source: Acta Cytol. 2004 March-April; 48(2): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085748

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Implementation of liquid-based cytology in the screening programme against cervical cancer in the County of Funen, Denmark, and status for the first year. Author(s): Hoelund B. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 October; 14(5): 269-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510891

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Impression cytology and ocular characteristics in ocular rosacea. Author(s): Kocak-Altintas AG, Kocak-Midillioglu I, Gul U, Bilezikci B, Isiksacan O, Duman S. Source: Eur J Ophthalmol. 2003 May; 13(4): 351-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872791

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Impression cytology of the ocular surface: a review. Author(s): Calonge M, Diebold Y, Saez V, Enriquez de Salamanca A, Garcia-Vazquez C, Corrales RM, Herreras JM. Source: Experimental Eye Research. 2004 March; 78(3): 457-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15106925

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Imprint cytology for rapid evaluation of lung and mediastinal lesions. Author(s): Tamiolakis D, Mikroulis D, Lambropoulou M, Bitzikas G, Didilis V, Kotini A, Papadopoulos N, Bougioukas G. Source: Minerva Med. 2003 April; 94(2): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858158

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Imprint cytology of the sentinel lymph node in the assessment of axillary node status in breast carcinoma. Author(s): Ravichandran D, Kocjan G, Falzon M, Ball RY, Ralphs DN. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2004 April; 30(3): 238-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15028302

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Imprint cytology versus frozen section: intraoperative analysis of sentinel lymph nodes in breast cancer. Author(s): Liang R, Craik J, Juhasz ES, Harman CR. Source: Anz Journal of Surgery. 2003 August; 73(8): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887528

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Increasing the clinical utility of the cervical smear cytology report--a cytopathologist's recommendations. Author(s): Malami SA, Adegbola TA, Mayun AA. Source: Niger J Med. 2003 January-March; 12(1): 58-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956010

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Infarction of acinic cell carcinoma in a patient infected with HIV: a complication of fine-needle aspiration cytology obscuring definitive diagnosis. Author(s): Rau AR, Pai RR, Nayak S. Source: Diagnostic Cytopathology. 2003 October; 29(4): 222-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506676

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Influence of stricture dilation and repeat brushing on the cancer detection rate of brush cytology in the evaluation of malignant biliary obstruction. Author(s): de Bellis M, Fogel EL, Sherman S, Watkins JL, Chappo J, Younger C, Cramer H, Lehman GA. Source: Gastrointestinal Endoscopy. 2003 August; 58(2): 176-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872082

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Insular carcinoma of the thyroid with a predominant microfollicular pattern: a diagnostic pitfall on cytology. Author(s): Jain S, Kumar N, Gupta S, Sodhani P, Aggarwal AK. Source: Acta Cytol. 2004 January-February; 48(1): 111-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969192

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Intracranial hydatidosis. Report of a case diagnosed on cerebrospinal fluid cytology. Author(s): Sherwani RK, Abrari A, Jayrajpuri ZS, Srivastava VK. Source: Acta Cytol. 2003 May-June; 47(3): 506-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789941

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Intraductal aspiration cytology and galactography for nipple discharge. Author(s): Baitchev G, Gortchev G, Todorova A, Dikov D, Stancheva N, Daskalova I. Source: Int Surg. 2003 April-June; 88(2): 83-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872900

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Intraoperative imprint cytology for evaluation of sentinel lymph nodes from visceral malignancies. Author(s): Levine EA, Shen P, Shiver SA, Waters G, Brant A, Geisenger KR. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 July-August; 7(5): 687-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850683

84

Cytology

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Intraoperative imprint cytology of sentinel nodes in breast cancer. Author(s): Barranger E, Antoine M, Grahek D, Callard P, Uzan S. Source: Journal of Surgical Oncology. 2004 June 1; 86(3): 128-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15170650

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Intraoperative pleural lavage cytology is an independent prognostic indicator for staging non-small cell lung cancer. Author(s): Lim E, Ali A, Theodorou P, Nicholson AG, Ladas G, Goldstraw P. Source: The Journal of Thoracic and Cardiovascular Surgery. 2004 April; 127(4): 1113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052210

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Intravascular papillary endothelial hyperplasia of the neck masquerading as malignancy on fine-needle aspiration cytology. Author(s): Suh KS, Shin KS, Park IA. Source: Diagnostic Cytopathology. 2003 July; 29(1): 14-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827709

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Juvenile granulosa cell tumor of the ovary: imprint cytology findings. Author(s): Shintaku M, Sangawa A, Matsumoto T, Ohtsuka K. Source: Acta Cytol. 2002 November-December; 46(6): 1173-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462106

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K statistic as a measure of quality control in cervicovaginal cytology. Author(s): Tamiolakis D, Anastasiadis P, Karamanidis D, Bounovas A, Romanidis K, Stellos K, Kotini A, Papadopoulos N. Source: Clin Exp Obstet Gynecol. 2001; 28(4): 229-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838745

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Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle aspiration cytology of thyroid follicular lesions. Author(s): Mehrotra A, Goel MM, Singh K. Source: Anal Quant Cytol Histol. 2002 August; 24(4): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12199321

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Ki-67 immunocytochemistry in liquid based cervical cytology: useful as an adjunctive tool? Author(s): Sahebali S, Depuydt CE, Segers K, Vereecken AJ, Van Marck E, Bogers JJ. Source: Journal of Clinical Pathology. 2003 September; 56(9): 681-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944552

Studies

85

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Kimura's disease. Diagnosis by aspiration cytology. Author(s): Deshpande AH, Nayak S, Munshi MM, Bobhate SK. Source: Acta Cytol. 2002 March-April; 46(2): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11917585

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Langerhans cell histiocytosis of the thyroid diagnosed by fine needle aspiration cytology. A case report. Author(s): Zhu H, Hu DX. Source: Acta Cytol. 2004 March-April; 48(2): 278-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085768

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Laser scanning cytometry for the detection of neoplasia in urologic cytology specimens. Author(s): Foster SS, Leiman G, Schwarz JE, St John T, Beatty BG. Source: Cancer. 2004 April 25; 102(2): 115-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15098256

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Liquid-based cervical cytology. Author(s): Klinkhamer PJ, Meerding WJ, Rosier PF, Hanselaar AG. Source: Cancer. 2003 October 25; 99(5): 263-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579292

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Liquid-based cytology and conventional cervical smears: a comparison study in an Asian screening population. Author(s): Cheung AN, Szeto EF, Leung BS, Khoo US, Ng AW. Source: Cancer. 2003 December 25; 99(6): 331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681939

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Liquid-based cytology findings of glassy cell carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis. Author(s): Ng WK, Cheung LK, Li AS. Source: Acta Cytol. 2004 January-February; 48(1): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969191

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Liquid-based cytology for the postirradiation surveillance of women with gynecologic malignancies. Author(s): Wright JD, Herzog TJ, Mutch DG, Gibb RK, Rader JS, Davila RM, Cohn DE. Source: Gynecologic Oncology. 2003 October; 91(1): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529673

86

Cytology

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Liquid-based cytology in breast fine needle aspiration. Comparison with the conventional smear. Author(s): Veneti S, Daskalopoulou D, Zervoudis S, Papasotiriou E, IoannidouMouzaka L. Source: Acta Cytol. 2003 March-April; 47(2): 188-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685187

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Liquid-based cytology: an Australian experience. Author(s): Farnsworth A. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 April; 14(2): 48-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12713474

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Liquid-based cytology: the new screening test for cervical cancer control. Author(s): McGoogan E. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2004 April; 30(2): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15087002

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Liquid-based cytology: where do we go from here? Author(s): Maksem JA. Source: Diagnostic Cytopathology. 1999 August; 21(2): 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425043

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Loop excision for high-grade squamous intraepithelial lesion on cytology: correlation with colposcopic and histologic findings. Author(s): Szurkus DC, Harrison TA. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1180-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748471

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Low sensitivity of the touch imprint cytology of the sentinel lymph node in breast cancer patients--results of a large series. Author(s): Zgajnar J, Frkovic-Grazio S, Besic N, Hocevar M, Vidergar-Kralj B, Gerljevic A, Pogacnik A. Source: Journal of Surgical Oncology. 2004 February; 85(2): 82-6; Discussion 87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755508

Studies

87

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Lymphoepithelioid cell lymphoma (Lennert's lymphoma). Report of a case with fine needle aspiration cytology. Author(s): Vaillo Vinagre A, Gutierrez Martin A, Perez Barrios A, Alberti Masgrau N, Ruiz Liso JM. Source: Acta Cytol. 2004 March-April; 48(2): 234-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085759

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Lysosomal hydrolase staining of conjunctival impression cytology specimens in keratoconus. Author(s): Shen JF, McMahon TT, Cheng EL, Sugar J, Yue BY, Anderson RJ, Begley C, Zhou J; Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group. Source: Cornea. 2002 July; 21(5): 447-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072717

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Mammary pseudoangiomatous stromal hyperplasia. A reappraisal of the fine needle aspiration cytology findings. Author(s): Ng WK, Chiu CS, Han KC, Chow JC. Source: Acta Cytol. 2003 May-June; 47(3): 373-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789917

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Management of atypical and low-grade cervical cytology. Author(s): Falkner CA, Walker JL. Source: Cancer Journal (Sudbury, Mass.). 2003 September-October; 9(5): 377-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14690312

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Measuring telomerase activity in various human tumors in routine histology and cytology. Author(s): Kovacs RB, Bollmann M, Speich N, Bollmann R, Bodo M, Sapi Z. Source: International Journal of Molecular Medicine. 2004 February; 13(2): 303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719139

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Methodologic aspects of evaluating brush samples from biliary strictures by cytology and DNA flow cytometry. Author(s): Bergquist A, Lindberg B, Castro J, Tribukait B. Source: Acta Cytol. 2004 May-June; 48(3): 341-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192949

88

Cytology

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Microsatellite analysis of urine sediment versus urine cytology for diagnosing transitional cell tumors of the urinary bladder. Author(s): Fornari D, Steven K, Hansen AB, Vibits H, Jepsen JV, Poulsen AL, Schwartz M, Horn T. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2004 February; 112(2): 148-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056232

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Molecular markers in cervical cytology. Author(s): Altiok S. Source: Clin Lab Med. 2003 September; 23(3): 709-28, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560536

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Monitoring patients for bladder neoplasms: what can be expected of urinary cytology consultations in clinical practice. Author(s): Malik SN, Murphy WM. Source: Urology. 1999 July; 54(1): 62-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414728

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Morphological spectrum of polyoma virus disease in renal allografts: diagnostic accuracy of urine cytology. Author(s): Drachenberg RC, Drachenberg CB, Papadimitriou JC, Ramos E, Fink JC, Wali R, Weir MR, Cangro CB, Klassen DK, Khaled A, Cunningham R, Bartlett ST. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 November; 1(4): 373-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099383

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Multiple loss of heterozygosity without K-ras mutation identified by molecular analysis on fine-needle aspiration cytology specimen of acinar cell carcinoma of pancreas. Author(s): Ohori NP, Khalid A, Etemad B, Finkelstein SD. Source: Diagnostic Cytopathology. 2002 July; 27(1): 42-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112815

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Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology. Author(s): Skacel M, Fahmy M, Brainard JA, Pettay JD, Biscotti CV, Liou LS, Procop GW, Jones JS, Ulchaker J, Zippe CD, Tubbs RR. Source: The Journal of Urology. 2003 June; 169(6): 2101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771727

Studies

89

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Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium. Author(s): Huvinen M, Makitie A, Jarventaus H, Wolff H, Stjernvall T, Hovi A, Hirvonen A, Ranta R, Nurminen M, Norppa H. Source: Mutagenesis. 2002 September; 17(5): 425-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202631

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Nasal cytology and genotoxic damage in nasal epithelium and leukocytes: asthmatics versus nonasthmatics. Author(s): Fortoul TI, Valverde M, Lopez Mdel C, Lopez I, Sanchez I, Avila-Costa MR, Avila-Casado Mdel C, Mussali-Galante P, Soria E, Rojas E. Source: International Archives of Allergy and Immunology. 2003 March; 130(3): 232-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660428

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Nasal cytology: description of a hyperchromatic supranuclear stria as a possible marker for the anatomical and functional integrity of the ciliated cell. Author(s): Gelardi M, Cassano P, Cassano M, Fiorella ML. Source: American Journal of Rhinology. 2003 September-October; 17(5): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599129

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Neoadjuvant chemotherapy for advanced ovarian cancer: the role of cytology in pretreatment diagnosis. Author(s): Schwartz PE, Zheng W. Source: Gynecologic Oncology. 2003 September; 90(3): 644-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678739

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New Bethesda terminology and evidence-based management guidelines for cervical cytology findings. Author(s): Stoler MH. Source: Jama : the Journal of the American Medical Association. 2002 April 24; 287(16): 2140-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966390

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New educational methods in cytopathology: a transnational training program in cervical cytology--CYTOTRAIN CD-ROM. Author(s): Chosia M. Source: Pol J Pathol. 2001; 52(4): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11915184

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NHS cervical screening programme to introduce liquid based cytology. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2003 October 25; 327(7421): 948. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576231

90

Cytology

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Nipple aspirate fluid cytology in breast carcinoma. Author(s): Krishnamurthy S, Sneige N, Thompson PA, Marcy SM, Singletary SE, Cristofanilli M, Hunt KK, Kuerer HM. Source: Cancer. 2003 April 25; 99(2): 97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704689

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Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings. Author(s): Ng WK, Lee CY, Li AS, Cheung LK. Source: Acta Cytol. 2003 November-December; 47(6): 1063-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674081

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Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. Author(s): Chow LS, Gharib H, Goellner JR, van Heerden JA. Source: Thyroid : Official Journal of the American Thyroid Association. 2001 December; 11(12): 1147-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186502

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Occult lymph node metastasis from desmoplastic small round cell tumor diagnosed by fine needle aspiration cytology. A case report. Author(s): Zeppa P, Lepore M, Vetrani A, Palombini L. Source: Acta Cytol. 2003 May-June; 47(3): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789940

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Ocular surface impression cytology. Author(s): McKelvie P. Source: Advances in Anatomic Pathology. 2003 November; 10(6): 328-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581822

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Oral cytology assessment by flow cytometry of DNA adducts, aneuploidy, proliferation and apoptosis shows differences between smokers and non-smokers. Author(s): Schwartz JL, Muscat JE, Baker V, Larios E, Stephenson GD, Guo W, Xie T, Gu X, Chung FL. Source: Oral Oncology. 2003 December; 39(8): 842-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679208

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Oral cytology in cannabis smokers. Author(s): Darling MR, Learmonth GM, Arendorf TM. Source: Sadj. 2002 April; 57(4): 132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12078330

Studies

91

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Oral exfoliative cytology in the diagnosis of paracoccidioidomycosis. Author(s): de Araujo MS, Mesquita RA, Correa L, de Sousa SO. Source: Acta Cytol. 2001 May-June; 45(3): 360-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393067

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Oral exfoliative cytology of smokers at discrete clinical stages using AgNOR staining. Author(s): Sethi P, Shah PM. Source: Indian J Dent Res. 2003 July-September; 14(3): 142-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15164655

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Oral exfoliative cytology procedures: conventional, brush biopsy and ThinPrep. Author(s): Kahn MA. Source: J Tenn Dent Assoc. 2001 Winter; 81(1): 17-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11324194

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Oral metastasis of breast carcinoma diagnosed by fine needle aspiration cytology. A case report. Author(s): Guimaraes AL, Perdigao PF, Siqueira FM, Castro WH, Gomez RS. Source: Acta Cytol. 2003 November-December; 47(6): 1074-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674083

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Origin of adenocarcinoma cells observed on cervical cytology. Author(s): Sasagawa M, Nishino K, Honma S, Kodama S, Takahashi T. Source: Acta Cytol. 2003 May-June; 47(3): 410-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789923

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Outcome of colposcopy in women presenting with postcoital bleeding and negative or no cytology--results of a 1-year audit. Author(s): Jha S, Sabharwal S. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2002 May; 22(3): 299-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521505

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Papillary cystic acinic cell carcinoma of the parotid gland diagnosed on fine needle aspiration cytology. Author(s): Singh UR, Bhattacharya TK, Shah SP. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 107-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027748

92

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Pelvic washing cytology of ovarian Sertoli-Leydig-cell tumor with retiform pattern: a case report. Author(s): Guo M, Lim JC, Wojcik EM. Source: Diagnostic Cytopathology. 2003 July; 29(1): 28-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827712

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Peritoneal cytology in patients with gastric cancer exposed to the serosa--a proposed new classification based on the local and distant cytology. Author(s): Yoshikawa T, Tsuburaya A, Kobayashi O, Sairenji M, Motohashi H, Noguchi Y. Source: Hepatogastroenterology. 2003 July-August; 50(52): 1183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846010

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Peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreas. Author(s): Meszoely IM, Lee JS, Watson JC, Meyers M, Wang H, Hoffman JP. Source: The American Surgeon. 2004 March; 70(3): 208-13; Discussion 213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055843

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Pitfalls in fine needle aspiration cytology. Author(s): Orell SR. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 173-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873307

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Postoperative bladder washing cytology after transurethral resection. Can it predict the recurrence of urothelial carcinoma? Author(s): Iczkowski KA, Katz G, Cascione CJ. Source: Acta Cytol. 2004 May-June; 48(3): 380-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15192954

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Postoperative cytology for drained fluid from the pancreatic bed after "curative" resection of pancreatic cancers: does it predict both the patient's prognosis and the site of cancer recurrence? Author(s): Ishikawa O, Wada H, Ohigashi H, Doki Y, Yokoyama S, Noura S, Yamada T, Sasaki Y, Imaoka S, Kasugai T, Matsunaga T, Takenaka A, Nakaizumi A. Source: Annals of Surgery. 2003 July; 238(1): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832972

Studies

93

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Primary malignant melanoma of uterine cervix: a rare entity diagnosed on fine needle aspiration cytology--report of a case. Author(s): Gupta S, Sodhani P, Jain S. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 153-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828726

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Primary pulmonary rhabdomyosarcoma diagnosed by fine-needle aspiration cytology. Author(s): Gray JA, Nguyen GK. Source: Diagnostic Cytopathology. 2003 September; 29(3): 181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951690

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Primitive neuroectodermal tumor of the kidney. Report of a case initially diagnosed by fine needle aspiration cytology. Author(s): Maly B, Maly A, Reinhartz T, Sherman Y. Source: Acta Cytol. 2004 March-April; 48(2): 264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085765

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Qualification of ASCUS. A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study. Author(s): Sherman ME, Solomon D, Schiffman M; ASCUS LSIL Triage Study Group. Source: American Journal of Clinical Pathology. 2001 September; 116(3): 386-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554167

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Quality assurance in gynecologic cytology. The value of cytotechnologistcytopathologist discrepancy logs. Author(s): Cibas ES, Dean B, Maffeo N, Allred EN. Source: American Journal of Clinical Pathology. 2001 April; 115(4): 512-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293898

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Quality control of cervical cytology in high-risk women. PAPNET system compared with manual rescreening. Author(s): Bergeron C, Masseroli M, Ghezi A, Lemarie A, Mango L, Koss LG. Source: Acta Cytol. 2000 March-April; 44(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10740599

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Quality indices in a cervicovaginal cytology service: before and after laboratory accreditation. Author(s): Tan KB, Chang SA, Soh VC, Thamboo TP, Nilsson B, Chan NH. Source: Archives of Pathology & Laboratory Medicine. 2004 March; 128(3): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987158

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Quality management in gynecologic cytology using interlaboratory comparison. Author(s): Jones BA, Davey DD. Source: Archives of Pathology & Laboratory Medicine. 2000 May; 124(5): 672-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10782146

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Quantitation of lipid-laden macrophages in evaluation of lower airway cytology specimens from pediatric patients. Author(s): Yang YJ, Steele CT, Anbar RD, Sinacori JT, Powers CN. Source: Diagnostic Cytopathology. 2001 February; 24(2): 98-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11169887

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Quantitation of spermatogenesis by DNA flow cytometry from fine-needle aspiration cytology material. Author(s): Dey P, Mondal AK, Singh SK, Vohra H. Source: Diagnostic Cytopathology. 2000 December; 23(6): 386-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074642

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Quantitative cytology in ovarian carcinoma ascitic fluids. Author(s): Kalogeraki A, Panayiotides J, Tzardi M, Tamiolakis D, Datseris G, Vlachonikolis J, Delides GS. Source: Anal Quant Cytol Histol. 2000 April; 22(2): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10800615

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Quantitative detection of disseminated cancer cells in the greater omentum of gastric carcinoma patients with real-time RT-PCR: a comparison with peritoneal lavage cytology. Author(s): Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, Hirai T, Yasui K, Kato T, Tatematsu M. Source: Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2002; 5(2): 69-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111581

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Quick aspiration cytology for thyroid nodules by modified Ultrafast Papanicolaou staining. Author(s): Maruta J, Hashimoto H, Yamashita H, Yamashita H, Noguchi S. Source: Diagnostic Cytopathology. 2003 January; 28(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508182

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Randomized controlled trials of HPV testing and Pap cytology: toward evidencebased cervical cancer prevention. Author(s): Franco EL. Source: International Journal of Cancer. Journal International Du Cancer. 2004 May 20; 110(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054862

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Rapid intraoperative diagnosis of tumors of the eye and orbit by squash and imprint cytology. Author(s): Vemuganti GK, Naik MN, Honavar SG, Sekhar GC. Source: Ophthalmology. 2004 May; 111(5): 1009-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15121381

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Rapid pre-screening: a validated quality assurance measure in cervical cytology. Author(s): Smith J, Nicholas D, Boyd K, Deacon-Smith R. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 October; 14(5): 275-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510892

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Risk stratification for bladder tumor recurrence, stage and grade by urinary nuclear matrix protein 22 and cytology. Author(s): Shariat SF, Casella R, Wians FH Jr, Ashfaq R, Balko J, Sulser T, Gasser TC, Sagalowsky AI. Source: European Urology. 2004 March; 45(3): 304-13; Author Reply 313. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036675

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Role of biliary brush cytology in primary sclerosing cholangitis. Author(s): Lal A, Okonkwo A, Schindler S, De Frias D, Nayar R. Source: Acta Cytol. 2004 January-February; 48(1): 9-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969174

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Role of fine needle aspiration cytology in the diagnosis of swellings in the salivary gland regions: a study of 712 cases. Author(s): Das DK, Petkar MA, Al-Mane NM, Sheikh ZA, Mallik MK, Anim JT. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2004 March-April; 13(2): 95-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755143

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Role of imprint cytology in the diagnosis of gastrointestinal tract malignancies. Author(s): Mysorekar VV, Dandekar CP, Satyaprakash BS, Sarkar A. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 37-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027716

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Role of repeat fine needle aspiration cytology in head and neck lesions: preliminary study. Author(s): Shykhon M, Macnamara M, El-Assy A, Warfield AT. Source: The Journal of Laryngology and Otology. 2004 April; 118(4): 294-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117469

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Role of socio-economic factors and cytology in cervical erosion in reproductive age group women. Author(s): Kulkarni RN, Durge PM. Source: Indian Journal of Medical Sciences. 2002 December; 56(12): 598-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514242

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Role of voided urine cytology in diagnosing primary urethral carcinoma. Author(s): Touijer AK, Dalbagni G. Source: Urology. 2004 January; 63(1): 33-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751342

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Salivary gland neoplasms with basaloid cell features: report of two cases diagnosed by fine-needle aspiration cytology. Author(s): Tawfik O, Tsue T, Pantazis C, Nuckols D, Younes S, Webb P. Source: Diagnostic Cytopathology. 1999 July; 21(1): 46-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405809

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Serial fine needle cytology in the diagnosis of esophageal cancer. Author(s): Stockeld D, Ingelman-Sundberg H, Granstrom L, Fagerberg J, Backman L. Source: Acta Cytol. 2002 May-June; 46(3): 527-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040648

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Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology. Author(s): Belinson JL, Qiao YL, Pretorius RG, Zhang WH, Rong SD, Huang MN, Zhao FH, Wu LY, Ren SD, Huang RD, Washington MF, Pan QJ, Li L, Fife D. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 November-December; 13(6): 819-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675319

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Spleen metastasis from thyroid carcinoma. Report of a case with diagnosis by fine needle aspiration cytology. Author(s): Mayayo E, Blazquez S, Gomez-Aracil V, Sauri A, Martinez S. Source: Acta Cytol. 2003 November-December; 47(6): 1116-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674093

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Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods. Author(s): Erkilic S, Ozsarac C, Kullu S. Source: Acta Cytol. 2003 November-December; 47(6): 1023-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674072

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Sputum cytology of patients with severe acute respiratory syndrome (SARS). Author(s): Tse GM, Hui PK, Ma TK, Lo AW, To KF, Chan WY, Chow LT, Ng HK. Source: Journal of Clinical Pathology. 2004 March; 57(3): 256-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990595

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Squash cytology of cerebellar haemangioblastoma. Author(s): Ortega L, Jimenez-Heffernan JA, Perna C. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2002 June; 13(3): 184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060085

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Squash cytology of Rosai-Dorfman disease in the sellar region. Author(s): Tanboon J, Chaipipat M, Wattanasirmkit V, Wongtabtim W, Shuangshoti S, Bunyaratavej K. Source: Acta Cytol. 2003 November-December; 47(6): 1143-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674101

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Suspicious urinary cytology with negative evaluation for malignancy in the diagnostic investigation of haematuria: how to follow up? Author(s): Nabi G, Greene D, O'Donnell MO. Source: Journal of Clinical Pathology. 2004 April; 57(4): 365-8. Erratum In: J Clin Pathol. J Clin Pathol. 2004 June; 57(6): 672. Donnel Mo [corrected to O'donnell Mo]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047737

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Synovial sarcoma of the thyroid. Report of a case with aspiration cytology findings and gene analysis. Author(s): Kikuchi I, Anbo J, Nakamura S, Sugai T, Sasou S, Yamamoto M, Oda Y, Shiratsuchi H, Tsuneyoshi M. Source: Acta Cytol. 2003 May-June; 47(3): 495-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789939

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Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women. Author(s): Pelit A, Bagis T, Kayaselcuk F, Dursun D, Akova Y, Aydin P. Source: Eur J Ophthalmol. 2003 May; 13(4): 337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872789

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The clinician's view: role of human papillomavirus testing in the American Society for Colposcopy and Cervical Pathology Guidelines for the management of abnormal cervical cytology and cervical cancer precursors. Author(s): Cox JT; American Society for Colposcopy and Cervical Pathology. Source: Archives of Pathology & Laboratory Medicine. 2003 August; 127(8): 950-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952506

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The cytology of pancreatic foamy gland adenocarcinoma. Author(s): Stelow EB, Pambuccian SE, Bardales RH, Debol SM, Mallery S, Lai R, Stanley MW. Source: American Journal of Clinical Pathology. 2004 June; 121(6): 893-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198363

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The diagnostic value of fine needle aspiration cytology (FNAC) in the assessment of palpable supraclavicular lymph nodes: a study of 218 cases. Author(s): Gupta RK, Naran S, Lallu S, Fauck R. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 August; 14(4): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873313

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The Dutch CISOE-A framework for cytology reporting increases efficacy of screening upon standardisation since 1996. Author(s): Bulk S, Van Kemenade FJ, Rozendaal L, Meijer CJ. Source: Journal of Clinical Pathology. 2004 April; 57(4): 388-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15047743

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The evaluation of liquid-based 'Cyto-SED' cytology of bronchioalveolar lavage specimens in the diagnosis of pulmonary neoplasia against conventional direct smears. Author(s): Astall E, Atkinson C, Morton N, Goddard MJ. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828724

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The triage of squamous cell abnormalities of cervical cytology by human papilloma virus screening. Author(s): Ozsaran AA, Dikmen Y, Akercan F, Zekioglu O, Terek MC, Mgoyi L, Altuglu I. Source: Eur J Gynaecol Oncol. 2003; 24(6): 535-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658597

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The use of fine-needle aspiration cytology and core biopsy in the assessment of highly suspicious mammographic microcalcifications: analysis of outcome for 182 lesions detected in the setting of a population-based breast cancer screening program. Author(s): Farshid G, Rush G. Source: Cancer. 2003 December 25; 99(6): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681944

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Thin-layer cytology and histopathology in the evaluation of abnormal uterine bleeding. Author(s): Garcia F, Barker B, Davis J, Shelton T, Harrigill K, Schalk N, Meyer J, Hatch K. Source: J Reprod Med. 2003 November; 48(11): 882-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686021

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Touch imprint cytology of axillary lymph nodes after neoadjuvant chemotherapy in patients with breast carcinoma. Author(s): Jain P, Kumar R, Anand M, Asthana S, Deo SV, Gupta R, Bhutani M, Karak AK, Shukla NK. Source: Cancer. 2003 December 25; 99(6): 346-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681942

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Ultrasound guided fine needle aspiration cytology for diagnosis of mass lesions of liver. Author(s): Talukder SI, Huq MH, Haque MA, Rahman S, Islam SM, Hossain GA, Sarker CB, Saleh AF, Rahman MM, Ali MS. Source: Mymensingh Med J. 2004 January; 13(1): 25-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747780

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Ultrasound-guided fine needle aspiration cytology combined with flow cytometric immunophenotyping for rapid characterization of deep-seated non-Hodgkin's lymphoma recurrence. Author(s): Picardi M, Del Vecchio L, De Renzo A, Zeppa P, Luciano L, Rotoli B. Source: Haematologica. 2003 March; 88(3): 356-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651281

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Urinary cytology associated with human polyomavirus and indinavir therapy in HIVinfected patients. Author(s): Filie AC, Wilder AM, Brosky K, Kopp JB, Miller KD, Abati A. Source: American Journal of Clinical Pathology. 2002 June; 117(6): 922-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047144

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Urine cytology in renal glomerular disease and value of G1 cell in the diagnosis of glomerular bleeding. Author(s): Nguyen GK. Source: Diagnostic Cytopathology. 2003 August; 29(2): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889042

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UroVysion multiprobe FISH in urinary cytology. Author(s): Bubendorf L, Grilli B. Source: Methods in Molecular Medicine. 2004; 97: 117-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15064489

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Use of a liquid-based, thin-layer Pap test in a community hospital. Impact on cytology performance and productivity. Author(s): Sass MA. Source: Acta Cytol. 2004 January-February; 48(1): 17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969176

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Use of the same archival papanicolanou smears for detection of human papillomavirus by cytology and polymerase chain reaction. Author(s): McDonald RL, Rose BR, Gibbins J, Baird PJ. Source: Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B. 1999 March; 8(1): 20-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10408789

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Use of ThinPrep monolayer technique and cytospin preparation in urine cytology: a comparative analysis. Author(s): Nassar H, Ali-Fehmi R, Madan S. Source: Diagnostic Cytopathology. 2003 March; 28(3): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619090

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Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing: a comparative study using simultaneously sampled histology materials. Author(s): Yoshida T, Fukuda T, Sano T, Kanuma T, Owada N, Nakajima T. Source: Cancer. 2004 April 25; 102(2): 100-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15098254

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Utility of serosal stamp cytology as an indicator for high-risk peritoneal metastasis in colorectal cancer surgery. Author(s): Ojima H, Sasaki S, Fujisawa T, Ishibashi Y, Masuda N, Asao T, Kuwano H. Source: Hepatogastroenterology. 2003 January-February; 50(49): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629998

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Value of brush border cytology for dominant strictures in primary sclerosing cholangitis. Author(s): Stiehl A. Source: Endoscopy. 1999 May; 31(4): 333-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10376464

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Value of brush cytology for dominant strictures in primary sclerosing cholangitis. Author(s): Ponsioen CY, Vrouenraets SM, van Milligen de Wit AW, Sturm P, Tascilar M, Offerhaus GJ, Prins M, Huibregtse K, Tytgat GN. Source: Endoscopy. 1999 May; 31(4): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10376457

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Value of fine-needle aspiration cytology of parotid gland masses. Author(s): Sergi B, Contucci AM, Corina L, Paludetti G. Source: The Laryngoscope. 2004 April; 114(4): 789. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15064645

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Value of image-guided needle aspiration cytology in the assessment of pelvic and retroperitoneal masses. A study of 112 cases. Author(s): Gupta RK, Cheung YK, alAnsari AG, Naran S, Lallu S, Fauck R. Source: Acta Cytol. 2003 May-June; 47(3): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789920

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Value of selective upper tract cytology for recognition of upper tract tumors after treatment of superficial bladder cancer. Author(s): Gogus C, Baltaci S, Sahinli S, Turkolmez K, Beduk Y, Gogus O. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 May; 10(5): 243-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694462

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Value of urethral wash cytology in the retained male urethra after radical cystoprostatectomy. Author(s): Lin DW, Herr HW, Dalbagni G. Source: The Journal of Urology. 2003 March; 169(3): 961-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576822

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Video-assisted thoracic needle aspiration cytology for malignancy of the peripheral lung. Author(s): Iwasaki A, Kamihara Y, Yoneda S, Kawahara K, Shirakusa T. Source: The Thoracic and Cardiovascular Surgeon. 2003 April; 51(2): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730817

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Visceral pleura invasion and pleural lavage tumor cytology by lung cancer: a prospective appraisal. Author(s): Riquet M, Badoual C, Le Pimpec Barthes F, Lhote FM, Souilamas R, Hubsch JP, Danel C. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 353-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607638

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Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India. Author(s): Basu PS, Sankaranarayanan R, Mandal R, Roy C, Das P, Choudhury D, Bhattacharya D, Chatterjee R, Dutta K, Barik S, Tsu V, Chakrabarti RN, Siddiqi M; Calcutta Cervical Cancer Early Detection Group. Source: International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. 2003 September-October; 13(5): 626-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675346

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Vitamin A deficiency among Kenyan children as detected by conjunctival impression cytology. Author(s): Munene RM, Adala HS, Masinde MS, Rana FS. Source: East Afr Med J. 2003 September; 80(9): 476-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640169

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Wait-and-see policy for the N0 neck in early-stage oral and oropharyngeal squamous cell carcinoma using ultrasonography-guided cytology: is there a role for identification of the sentinel node? Author(s): Nieuwenhuis EJ, Castelijns JA, Pijpers R, van den Brekel MW, Brakenhoff RH, van der Waal I, Snow GB, Leemans CR. Source: Head & Neck. 2002 March; 24(3): 282-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11891961

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Warthin-like tumour of the thyroid--the fine needle aspiration cytology features. Author(s): Pai RR, Lobo FD, Upadhyay K, Muniappa M. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2001 April; 12(2): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284957

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Warty (condylomatous) carcinoma of the cervix. A review of 3 cases with emphasis on thin-layer cytology and molecular analysis for HPV. Author(s): Ng WK, Cheung LK, Li AS. Source: Acta Cytol. 2003 March-April; 47(2): 159-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685182

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Water vs gel lubricant for cervical cytology specimens. Author(s): Tavernier LA, Connor PD, Gates D. Source: The Journal of Family Practice. 2003 September; 52(9): 701-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967542

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Whipple's disease: benefit of the fine-needle aspiration cytology from lymph nodes. Author(s): Colombat M, Carton S. Source: Clin Exp Pathol. 1999; 47(5): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598371

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Wilms' tumor in adults: aspiration cytology and cytogenetics. Author(s): Li P, Perle MA, Scholes JV, Yang GC. Source: Diagnostic Cytopathology. 2002 February; 26(2): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11813327

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Working as an advanced biomedical science practitioner in cervical cytology. Author(s): Symonds M. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 2003 June; 14(3): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828717

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CHAPTER 2. ALTERNATIVE MEDICINE AND CYTOLOGY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to cytology. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to cytology and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “cytology” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to cytology: •

Women's experiences of abnormal cervical cytology: illness representations, care processes, and outcomes. Author(s): Karasz A, McKee MD, Roybal K. Source: Ann Fam Med. 2003 November-December; 1(4): 196-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055408

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to cytology; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 3. DISSERTATIONS ON CYTOLOGY Overview In this chapter, we will give you a bibliography on recent dissertations relating to cytology. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “cytology” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cytology, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Cytology ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to cytology. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Acetylcholinesterase and the basal ganglia from cytology to function by Lehmann, John; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49981

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Automated prescreening of cervical cytology specimens by Poulsen, Ronald S; PhD from MCGILL UNIVERSITY (CANADA), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15968

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Studies on morphology, cytology and formation of spores in the genera Pleurage, Sordaria, and Sporormia by Patil, Lalita G; ADVDEG from MCGILL UNIVERSITY (CANADA), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK05004

•

The cytology of spermatogenesis and ultrastructure of the seminiferous epithelium in reptiles by Gribbins, Kevin Michael, PhD from UNIVERSITY OF CINCINNATI, 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/3093369

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The effect of temperature on the growth, cytology and metabolism of Marquillo x Kenya Farmer wheat dwarf by Mahon, John David; ADVDEG from QUEEN'S UNIVERSITY AT KINGSTON (CANADA), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08692

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The life cycle and cytology of brachyallomyces by Flanagan, Patrick W; ADVDEG from MCGILL UNIVERSITY (CANADA), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK03121

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The life cycle and cytology of Nowakowskiella elegans and Cladochytrium replicatum by Lucarotti, Christopher John; PhD from MCGILL UNIVERSITY (CANADA), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK54848

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The life cycle and cytology of Rhizophlyctis by Boylan, Brendan V; PhD from MCGILL UNIVERSITY (CANADA), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20667

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Three AI approaches for improving classification decisions concerning cytology personnel according to United States federal law (CLIA'88): An integrative study by EL Etribi, Mohamed A., PhD from CITY UNIVERSITY OF NEW YORK, 1998, 137 pages http://wwwlib.umi.com/dissertations/fullcit/9908311

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 4. PATENTS ON CYTOLOGY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.4 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “cytology” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cytology, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Cytology By performing a patent search focusing on cytology, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

4Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on cytology: •

Apparatus for detecting bubbles in coverslip adhesive Inventor(s): Kuan; Chih-Chau L. (Redmond, WA), Rosenlof; Mikel D. (Boulder, CO) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,566,249 Date filed: September 20, 1994 Abstract: The detection of bubbles in coverslip adhesive. Bubbles in coverslip adhesive may span large areas of the coverslip. An automated cytology system acquires 4 x gray scale images of the slide. Image conditioning is then performed. The conditioned gray scale image is binomially filtered providing a binomial filtered image. The gray scale image is subtracted from the binomial filtered image to produce a high pass enhanced image. An object mask detection is then performed on the high pass enhanced image. Objects are classified to identify bubble edgest. Multiple detections of bubble edges are pieced together to detect bubbles much larger than the area covered by a single image from the detector and the microscope lens. Bubbles are located even if low level image analysis shows gaps in the edges. The cytological system fills in significant gaps in the detected bubble edges. The result is then used for further processing by the automated cytology system. Excerpt(s): The invention relates to an automated microscope cytological classifier and, more particularly, to an automated cytological classifier that includes an apparatus for detecting bubbles in coverslip adhesive. Bubbles, or other voids in coverslip adhesive used to hold coverslips to individual microscope slides, add extra air to glass surfaces and in other ways change the way objects are resolved by a microscope objective. For a system making precise measurements of objects in the specimen, these changes make measurements on the objects within the voids unreliable and therefore unusable. The edges of the bubbles are themselves resolved as heavy dark objects which are not of interest to the system analyzing the specimen. Therefore, it is undesirable to spend time trying to focus and analyze the bubble edges at high magnification. Web site: http://www.delphion.com/details?pn=US05566249__

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Apparatus for mixing and separating particulate matter from a fluid Inventor(s): Guirguis; Raouf A. (Vienna, VA), MacLean-Blevins; Mark T. (Westminster, MD) Assignee(s): LaMina, Inc. (Herndon, VA) Patent Number: 6,296,764 Date filed: November 4, 1998 Abstract: An apparatus for simultaneously processing a plural number of samples, each of the samples including a fluid containing particulate matter. The apparatus is useful in cytology to collect a uniform monolayer of cells from a biological fluid. Each of a plural number of processing assemblies (corresponding to the plural number of samples) comprises a container, an agitator rotatable relative to the container for contacting and dispersing particulate matter in the fluid, a filter assembly including a filter for collecting particulate matter, and a pump for moving the fluid through the filter. Each

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container is supported on a separate container receiver, and each pump is engaged by a separate pump engagement. A rotary driver effects relative rotation of the agitators and their respective containers simultaneously to mix the samples in the containers. Excerpt(s): The present invention is directed to an apparatus and method for collecting a uniform monolayer of particulate matter. In particular, the present invention is directed to an apparatus and manual or semi-automatic method for collecting a uniform monolayer of cells from biological fluids and preparing the monolayer of cells for use in cytological protocols. In a wide variety of technologies, the ability and/or facility for separating matter, typically particulate matter, from a fluid is a critical component in the ability to test for the presence of substances in the fluid. Too often, interference associated with sample preparation obscures the target cells to such a degree that the process is not sufficiently reliable, or too costly. Such a scenario applies to many other fields which involve detection and/or diagnosis, including environmental testing, radiation research, cancer screening, cytological examination, microbiological testing, and hazardous waste contamination, to name just a few. Web site: http://www.delphion.com/details?pn=US06296764__ •

Apparatus for stricture diagnosis and treatment Inventor(s): Rowland; Christopher A. (Marlborough, MA), Tolkoff; M. Joshua (Brookline, MA), Zaslavsky; Ella (Marblehead, MA) Assignee(s): Boston Scientific Corporation (Natick, MA) Patent Number: 5,427,115 Date filed: September 13, 1993 Abstract: Apparatus for use in the diagnosis and treatment of strictures in a biliary duct, urinary tract or pancreatic tract. The apparatus includes a dual lumen catheter device. One lumen size is sized to accommodate a guidewire. A second, parallel lumen has a non-circular cross-section and carries a cytology brush at one end that couples through an operator to a manipulator at another end. The cytology brush has an effective diameter that is greater than the diameter of the catheter device. Brush cytology samples are obtained without removing the guidewire from a stricture and without introducing any relative motion between the guidewire and the catheter. As the cytology brush is retracted into the non-circular lumen, its bristles compact around the operator for storage within the lumen. A predetermined arrangement of markers at the distal end of the catheter facilitates the measurement of stricture length by direct endoscopic visualization. Excerpt(s): This invention generally relates to the diagnosis and treatment of strictures in biliary ducts and urinary or pancreatic tracts and more particularly to apparatus that is useful in such diagnoses and treatment. If a stricture forms in an individual's biliary duct, urinary tract or pancreatic tract, flow through the duct or tract can stop. One step used in the diagnosis and treatment of symptoms resulting from such a stricture is a determination of whether the cells in the stricture are malignant. One methodology for diagnosing such malignancy involves brush cytology performed for example, by a cytology brush apparatus as described in U.S. Pat. No. 4,763,670. Thereafter the physician may place a stent in the vessel to open or dilate the stricture. Apparatus for placing such a stent is described in U.S. Pat. No. 5,234,457. During the diagnosis and treatment of a stricture in the biliary duct, urinary and pancreatic tracts, a physician initially introduces an endoscope with viewing and working channels through various

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vessels to position the distal end of the endoscope closely adjacent the proximal side of the stricture. In this discussion the phrases "proximal" and "distal" are applied in terms of the apparatus and the physician. Consequently the proximal end of the apparatus is located externally of the patient for direct manipulation by the physician. Next the physician may perform endoscopic retrograde cholangiopancreatography (ERCP) or transhepatic cholangiography (THC) in the biliary tree or retrograde cystography in the urinary tract. The physician may, prior to or during such procedures, locate the stricture by the injection of contrast media. In addition, the physician may advance an ERCP cannula or similar catheter-like device through the stricture either over a previously placed guidewire or independently of a guidewire. Web site: http://www.delphion.com/details?pn=US05427115__ •

Apparatus for the identification of free-lying cells Inventor(s): Bannister; Wendy R. (Seattle, WA), Kuan; Chih-Chau L. (Redmond, WA), Lee; Shih-Jong J. (Bellevue, WA), Meyer; Michael G. (Seattle, WA), Oh; Seho (Mukilteo, WA), Wilhelm; Paul S. (Kirkland, WA) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,978,497 Date filed: September 20, 1994 Abstract: A free-lying cell classifier. An automated microscope system comprising a computer and high speed processing field of view processors identifies free-lying cells. An image of a biological specimen is obtained and the image is segmented to create a set of binary masks. The binary masks are used by a feature calculator to compute the features that characterize objects of interest including free-lying cells, artifacts and other biological objects. The objects are classified to identify their type, their normality or abnormality or their identification as an artifact. The results are summarized and reported. A stain evaluation of the slide is performed as well as a typicality evaluation. The robustness of the measurement is also quantified as a classification confidence value. The free-lying cell evaluation is used by an automated cytology system to classify a biological specimen slide. Excerpt(s): The invention relates to an automated cytology system and more particularly to an automated cytology that identifies and classifies free-lying cells and cells having isolated nuclei on a biological specimen slide. One goal of a Papanicolaou smear analysis system is to emulate the well established human review process which follows standards suggested by The Bethesda System. A trained cytologist views a slide at low magnification to identify areas of interest, then switches to higher magnification where it is possible to distinguish normal cells from potentially abnormal ones according to changes in their structure and context. In much the same way as a human reviews Papanicolaou smears, it would be desirable for an automated cytology analysis system to view slides at low magnification to detect possible areas of interest, and at high magnification to locate possible abnormal cells. As a cytologist compares size, shape, texture, context and density of cells against established criteria, so it would be desirable to analyze cells according to pattern recognition criteria established during a training period. The invention identifies and classifies free-lying cells and cells having isolated nuclei on a biological specimen: single cells. Objects that appear as single cells bear the most significant diagnostic information in a pap smear. Objects that appear as single cells may be classified as being either normal cells, abnormal cells, or artifacts. The invention also provides a confidence level indicative of the likelihood that an object has

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been correctly identified and classified. The confidence level allows the rejection of slides having only a few very confident abnormal cells. The staining characteristics of the slide are also evaluated. The invention first acquires an image of the biological specimen at a predetermined magnification. Objects found in the image are identified and classified. This information is used for subsequent slide classification. Web site: http://www.delphion.com/details?pn=US05978497__ •

Aspiration needle and method Inventor(s): Gandhi; Deepak (San Jose, CA), Imran; Mir A. (Palo Alto, CA), Powles; Trevor J. (Chipstead Surrey, GB), Syed; Baber R. (Palo Alto, CA) Assignee(s): Advanced Cytometrix, Inc. (Irvine, CA) Patent Number: 5,902,279 Date filed: April 13, 1995 Abstract: An aspiration needle for use in collecting larger cell samples with a source of vacuum for fine needle aspiration cytology without increasing the size of the needle having a rigid elongate tubular member having distal and proximal extremities. The tubular member has a bore extending therethrough from the distal extremity to the proximal extremity and has an opening at the distal extremity in communication with the bore. A body is secured to the proximal extremity of the tubular member and forms a chamber therein in communication with and in close proximity to the opening into the bore of the tubular member. The chamber is formed by a sloping uninterrupted wall leading distally to the opening to the bore of the tubular member. The body includes a hub proximal of the chamber for receiving the source of vacuum and for establishing communication between the source of vacuum and the chamber. The body has an enlarged portion adjacent the proximal extremity of the tubular member permitting viewing of the chamber in the vicinity of the proximal extremity of the tubular member to facilitate observation of aspirate as it is collected in the chamber. Excerpt(s): This invention relates to an aspiration needle and method for use in fine needle aspiration cytology. Fine needle aspiration cytology has heretofore been utilized as a standard technique for the diagnosis of cancer utilizing a standard 23 gauge intravenous needle attached to a standard 10 milliliter syringe. In such a technique, the intravenous needle is passed through the skin into the tumor. The barrel of the syringe is withdrawn 3 or 4 milliliters while attached to the needle as the needle is passed three or four times through the tumor. This procedure sucks up a small amount of tissue fluid together with loose cells into the needle with some concurrent spillage up into the nozzle of the syringe. The needle is then removed from the tumor and detached from the syringe. Air is then drawn up into the syringe. The needle is reattached and the small amount of fluid with cells therein in the needle is forced out of the needle by operation of the syringe and blown onto a microscopic slide. The small amount of fluid is then smeared against another slide to produce a film on both slides which is then air dried and appropriately stained. Typically an accurate analysis of the lump can be made from a microscopic examination of these slides by an expert. In such a procedure it has been found that with a standard 23 gauge needle, the volume of the needle is often exceeded by the aspirate so that the sample passes up into the socket of the needle connected to the syringe and is partly entrapped therein preventing expression of the sample onto the slide. Also, it has been found that in many cases, the sample so obtained is inadequate to provide a clear diagnosis. Furthermore, newly developed immunocytochemical techniques for detecting proteins in cells can be used on

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cytological preparations for predicting growth characteristics, prognosis and likely response to treatment. These techniques require larger numbers of cells, than are currently obtained using standard aspiration equipment. Utilizing such standard intravenous needles, it has only been possible to obtain something in the order of 5,00010,000 cells which is only adequate for cytodiagnoses in about 60-70% of the patients. There is therefore need for a new and improved aspiration needle which will make it possible to obtain larger cell samples without increasing the external size of the needle. In addition, it has been found that the syringes utilized with such aspiration needles have been difficult to use during such aspiration procedures. There is therefore also a need for a new and improved syringe for use with the improved aspiration needle. In general, it is an object of the present invention to provide an aspiration needle and method for use in fine needle aspiration cytology. Web site: http://www.delphion.com/details?pn=US05902279__ •

Automated slide staining system and method thereof Inventor(s): Bertolino; A. John (Blairsville, PA), Edwards; Peter S. (Tallahassee, FL), Premus; Jerry C. (Scottdale, PA), Seager; Lloyd (Greensburg, PA) Assignee(s): Fisher Scientific Company L.L.C. (Pittsburgh, PA) Patent Number: 6,387,326 Date filed: February 9, 2000 Abstract: The present invention relates to an automatic slide staining system that will process stained slides, such as cytology or histology specimens. The invention includes a slide storage device, a slide transport apparatus, and a first platen including a plurality of staining stations. The stained slides are placed in the storage device and then are removed and processed at various stations via the transport apparatus. The invention can be altered so that a cover slip apparatus can be incorporated within the system. This permits a cover slip to be placed on the stained slide after a complete transverse of the slide staining stations. Excerpt(s): The present invention relates to a system for staining slides of human tissue specimens, and more particularly for staining histology and cytology tissue specimens on a slide for subsequent microscopic examination. Throughout the United States steps are being taken to improve Slide Staining Systems for subsequent pathologic examination in medical laboratories and hospitals. The primary cost component of preparing and staining a slide is labor. Accordingly, many efforts have been devoted to reduce the labor cost component of preparing a slide. With the advent of cost containment throughout the health-care industry, renewed efforts are being made to examine all direct labor cost areas with a focus on reducing the amount of labor heretofore involved, and the associated cost. For example, U.S. Pat. No. 4,190,472 issued to Slonicki, discloses an automated system for the application of cover glasses on histological and cytological slides. Patent '472 discloses a processing area wherein a slide that has been stained previously is progressively turned 90 degrees to mate with a cover glass to insure a contamination free tissue specimen. Web site: http://www.delphion.com/details?pn=US06387326__

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•

Bisulfite-based tissue fixative Inventor(s): Hartman; Anthony L. (Tucson, AZ), Jones; Christine R. (Tucson, AZ), Klotz; Janis L. (Tucson, AZ) Assignee(s): Ventana Medical Systems, Inc. (Tucson, AZ) Patent Number: 5,432,056 Date filed: November 15, 1993 Abstract: The present invention provides a bisulfite-based tissue fixative that improves morphology, antigen retention, and antigenicity. The fixative is suitable for use with sections of frozen tissue, cytology preparations (including touch preparations and blood smears) and other specimens used for immunohistochemical analysis. The fixative comprises an acidic buffer and a bisulfite salt in an effective amount for tissue fixation. In a preferred embodiment, the tissue fixative comprises a bisulfite salt in a concentration of from about 0.01 to about 0.25M, preferably, 0.02 to 0.25M, in an acidic buffer having a pH of from about 2 to about 6. Excerpt(s): This invention relates to a tissue fixative solution that improves morphology of non-formalin fixed tissues while retaining antigen and preserving antigenicity. There are two general categories of histochemical specimens. The most common is fixed, paraffin-embedded tissue specimens. These specimens are fixed, (usually using a formalin-based fixative), dehydrated to xylene, embedded in paraffin, sectioned onto a slide, deparaffinized, rehydrated, and stained. The second category includes preparations which are fresh tissues and/or cells, which generally are not fixed with aldehyde-based fixatives. Such specimens are either placed directly on a slide or coverslip, or frozen and sectioned onto slides. Such specimens are then fixed, usually with an alcohol- or acetone-based fixative, and stained. These specimens commonly include biopsy materials which may be analyzed while the surgical procedure is in progress (frozen sections), cytological preparations (including touch preparations and blood smears), and tissues which are to be immunohistochemically analyzed. Although buffered formaldehyde-based fixative solutions at pH's of 7.0 or greater (e.g., 10% neutral buffered formalin (NBF), 1-4% paraformaldehyde, Zamboni's, Bouin's, B5, Hollande's) provide excellent results for conventional staining methods, these fixatives are problematic for use with antibody staining methods as they covalently modify and cross link the antigens. This often results in the direct alteration of the epitope(s) or epitopic accessibility, either of which prevents antibody recognition and/or binding. Thus, antibodies are unable to detect many antigens present in tissues fixed using aldehyde-based fixatives. Web site: http://www.delphion.com/details?pn=US05432056__

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Catheter with simultaneous brush cytology and scrape biopsy capability Inventor(s): Parasher; Vinod K. (Long Neck Rd.-Suite #1, Millsboro, DE 19966) Assignee(s): none reported Patent Number: 5,535,756 Date filed: January 6, 1994 Abstract: A medical device performs simultaneous brush cytology and scrape biopsy on structures within an organic duct by collecting cells and tissue on a brush having irregular semi-rigid bristles, preferably formed as the hook portion of a hook and pile

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fastener (e.g., the hook portion of a Velcro pad). A wire guided catheter has a brush strip located near a distal end for insertion into the duct. Once the distal end and brush are positioned at a selected location within the duct, the catheter is pushed and pulled back and forth to gather cells and scrapings from the selected location, which accumulate in the irregular bristles. The catheter can be enclosed in a retractable sleeve during insertion and/or withdrawal. An enlargement at the distal end of the catheter assists in opening the duct to admit the brush. A radio-opaque marker is externally detectable to assist in locating the brush at the selected location. The relatively stiff irregular bristles improve the extent to which cells and tissues can be collected and permit collection of enough tissue to provide a biopsy sample, without substantial risk of perforation of the duct. Excerpt(s): This invention relates to devices for collecting cell samples from internal organs, and in particular to a catheter capable of simultaneously performing brush cytology and scrape biopsies of structures within biological ducts, employing a polymeric hook pad with relatively stiff irregularly shaped bristles for collecting cells from a sample site. More particularly, a wire guided catheter having a hook pad of a hook and pile fastener (e.g., Velcro) at its distal end is used for abrading against the duct walls to collect cells and tissue. It is sometimes necessary to collect a sampling of cells from internal organs, typically using an endoscope or laparoscope to obtain access to the site to be sampled, for laboratory analysis in connection with a diagnosis. In connection with certain bodily ducts, a tumor in the tissue of the duct or in tissues adjacent the duct may present as a narrowing or stricture of the duct at a localized area. Cancer of the bile duct or the pancreatic ducts, for example, present as a narrowing or stricture. Similarly, strictures can be seen in the esophagus, the stomach, the colon, and other duct-like organs. It is useful in connection with diagnosis to examine the cells at a stricture to better assess its cause. The brush can be placed in a sleeve to assist in guidance to the sample site, to avoid picking up cells from areas other than the stricture, and to protect the sample after it is collected. The sleeve can have one or more radio-opaque marks to help in placing the brush at the stricture. More particularly, fluoroscopy is used to visualize the location of the sleeve by the radio-opaque mark and therefore to assist in placing the brush in the stricture. Web site: http://www.delphion.com/details?pn=US05535756__ •

Cervical specimen self-sampling device (pap tampon) Inventor(s): Fournier; Arthur M. (P.O. Box 016700 (R700) Assignee(s): none reported Patent Number: 6,155,990 Date filed: December 7, 1998 Abstract: A human female cervical specimen gathering device is disclosed which can be self administered by women. The device consists of a cardboard tube that houses a retractable sponge, The handle is adapted to allow it to serve as a screw-cap lid, once the device is inserted into a conical tube containing fixative or preservative. After transport to the lab the tube call easily be agitated to liberate cells, centrifuged, and prepared as a thin smear for cytology or DNA probes. Excerpt(s): Screening for cervical cancer in women using cytological techniques has been possible for more than 40 years. The papanicolau test (pap test) has allowed for a significant reduction in mortality ill women from cervical cancer. Prior to the pap test,

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cervical cancer was the most common cause of cancer deaths in women. In countries where pap smears arc available, mortality from cervical cancer is negligible. In spite of this progress, there are several problems with the present technology. Conventional pap tests show a high percentage of smears of undetermined significance that requires further testing. This problem has led to the development of "thin prep" technology. Thin prep technology requires that cells be immersed in fixative and centrifuged prior to analysis. Other advances in diagnostic technology are the discovery of DNA probes for human papilloma virus (HFV), the causative agent of cervical cancer, and for chlamydia, a common infection in women. Tests for HPV may soon replace conventional pap smears as the initial screening test for cervical cancer. Collection of cytologic specimens currently requires a speculum examination which is frequently uncomfortable and embarrassing for women, It is also relatively expensive, since it requires the services of a physician or nurse practitioner. Finally, the specimen obtained is applied directly to a glass slide, which is not compatible with automated cytologic analysis or necessary for HPV assay. The same problems of discomfort, embarrassment, expense and processing also apply to the obtaining of specimens to diagnose vaginal infections such as candidiasis, gonorrhea, human papilloma virus and chlamydia. Prior self sampling devices (described in the next section) were either designed prior to the invention of thin prep and HPV assay technologies or designed specifically to obtain a specimen in the setting of a conventional speculum examination. Given these problems, there is a need for an improved, inexpensive self sampling device which asymptomatic women can use in the privacy of their home that is adaptable to automated cytology methods (thin smear), HPV assay and microbial culture. This application (discloses just such an improvement. Web site: http://www.delphion.com/details?pn=US06155990__ •

Computer system and computer-implemented process for analyzing results of cytology tests for performance evaluation of cytologists Inventor(s): Cibas; Edmund S. (Boston, MA) Assignee(s): The Brigham & Women's Hospital, Inc. (Boston, MA) Patent Number: 6,468,208 Date filed: May 26, 1999 Abstract: The evaluation of the performance of cytotechnologists and cytopathologists is obtained through statistical analyses of a computer system database including data representative of diagnosis by the cytotechnologists and cytopathologists. The statistical analyses provide objective measures of performance that aid in improving the quality of evaluation in the cytology laboratory. The locator skills, interpretive skills, volume statistics and productivity of the cytotechnologists is evaluated based on false-negative fraction information, divergent percentage calculations, average scores and kappa values, z scores and pro-rata workload measurements. The accuracy and performance of the cytopathologists is evaluated through the use of receiver operating characteristic curves and positive predictive values. Excerpt(s): One function performed in cytology laboratories is the analysis of cervicovaginal smear (i.e., pap) slides to identify cell abnormalities. Each cytology laboratory may include a number of cytotechnologists, who perform an initial review of pap-smear slides to provide provisional diagnoses of the slides. The provisional diagnoses generally fall into the categories of unsatisfactory (i.e., the specimen on the slide was not substantial enough to accurately diagnose), normal/negative (i.e., the

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specimen included no abnormal cells) or abnormal/positive (i.e., the specimen included some number of abnormal cells). Under federal law, cytotechnologists may release negative diagnoses, while cases having positive diagnoses are always reviewed by a senior cytopathologist. Because the negative diagnoses are not generally subject to a second review, there exists the risk that cases that actually showed an abnormality could be released as negative. Because this risk exists, the federal government requires that all cytology laboratories perform specific exercises in quality control to guarantee that the analyses are consistently accurate. One method of maintaining quality control is through a slide audit, where a randomly selected set of slides, originally identified as negative, is re-screened to determine whether, in fact, the slides indicate positive findings of cell abnormality. Another method of maintaining quality control is to periodically perform performance evaluations of cytotechnologists. These performance evaluations have historically been performed by cytopathologists, and are generally subjective in nature. No consistent methods have been applied to evaluating the performance of the individual cytopathologists in the laboratory. It would be desirable to determine an improved method for providing performance evaluations of cytotechnologists and cytopathologists ("cytologists") in a cytology laboratory in order to improve the quality of evaluation of cervicovaginal smears. Web site: http://www.delphion.com/details?pn=US06468208__ •

Cytological slide scoring apparatus Inventor(s): Bannister; Wendy R. (Seattle, WA), Frost; Keith L. (Seattle, WA), Hayenga; Jon W. (Kent, WA), Kuan; Chih-Chau L. (Redmond, WA), Lee; Shih-Jong J. (Bellevue, WA), Meyer; Michael G. (Seattle, WA), Nelson; Larry A. (Bellevue, WA), Ortyn; William E. (Devall, WA), Wilhelm; Paul S. (Kirkland, WA) Assignee(s): Neo Path, Inc. (Redmond, WA) Patent Number: 5,933,519 Date filed: June 3, 1997 Excerpt(s): The currently the well established human review process for Papanicolaou smear analysis follows standards recommended by the Bethesda System. A trained cytotechnologist systematically views a slide at low magnification to identify areas of interest. When an area of interest is identified, the cytotechnologist views the area at high magnification where it is possible to distinguish abnormal cells according to changes in their structure and context. In much the same way as a human reviews Papanicolaou smears, it is one motivation of the invention to scan slides at low magnification to detect possible areas of interest, then at high magnification, to scan those areas to locate possible abnormal cells or other cells of interest. As a cytotechnologist compares size, shape and density of cells against established criteria, it is an additional motive of the invention to compare objects according to criteria established during a training process. The invention detects areas of interest at low magnification, locating possible abnormal cells or other cells of interest using image processing and statistical pattern recognition techniques. Next, at high magnification, the areas identified at low magnification are re-examined. The information from the low magnification and high magnification scans is collated and a determination is made about the slide--whether it is normal, abnormal, contains endocervical component, and so forth. The invention also provides a method and apparatus to train object feature and slide feature classifiers. The invention provides an automated cytology system that can

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process training slides for use in a feed back classifier development environment. The invention also can classify endocervical groups of cells. Web site: http://www.delphion.com/details?pn=US05933519__ •

Cytology centrifuge apparatus Inventor(s): Kelley; Thomas F. (Canton, MA), Petithory; Henry A. (Southborough, MA), Soares; Todd W. (Milford, MA) Assignee(s): Norfolk Scientific, Inc. (Norwood, MA) Patent Number: 5,679,154 Date filed: December 21, 1995 Abstract: Removed cytology centrifuge apparatus includes single or multiple well cell concentrators for being rotated by a centrifugal spinner. A rotor is removably supported by the spinner for rotation and is adapted to receive two or four cell concentrators. The rotor supports the cell concentrators in an unrestrained manner, thereby enhancing the ease of use and flexibility of the apparatus. The cell concentrator is shaped to rest stably on a planar surface in a tilted manner so that a fluid specimen contained therein is prevented from contacting the slide prior to centrifugation. Each cell concentrator includes a chamber having at least one fluid receiving aperture and at least one fluid expulsion aperture. The chamber is secured to a backing plate by a fastening mechanism, with the slide sandwiched therebetween. In one embodiment, the chamber is hinged to the backing plate. Also described is a bibulous pad interposed between the chamber and the slide in order to absorb excess sample fluid. Excerpt(s): This invention relates generally to centrifuge apparatus and more particularly, to improved cytology centrifuge apparatus. Centrifugation of cells suspended in a carrier fluid in order to deposit the cells on a microscope slide for subsequent analysis is known in the field of cytology. Exemplary cell suspension fluids include normal body fluids such as synovial fluid or cerebrospinal fluid, abnormal fluids such as ascites fluid resulting from a cancer, or artificial fluids such as cell cultures. During centrifugation, the carrier fluid is forced against the slide causing cells suspended therein to attach to the slide, preferably in a substantially monolayer configuration. Subsequent processing may include staining the deposited cells with staining reagents to enhance selected cell attributes prior to microscopic analysis of the cells. Generally, centrifugation apparatus includes an electromechanical spinner for supporting a rotor and having a motor for rotating the rotor. The rotor includes a mechanism for mounting and restraining one or more sample chambers, referred to hereinafter as cell concentrators, for rotation. The cell concentrators include generally, a chamber having a fluid receiving aperture through which a fluid specimen is added and a fluid expulsion aperture through which the fluid is expelled during centrifugation, a microscope slide disposed in fluid communication with the fluid expulsion aperture, and a securing mechanism for securing the slide to the chamber. Web site: http://www.delphion.com/details?pn=US05679154__

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Cytology chamber with port to receive collection bottle and method of use Inventor(s): Hayes; William J. (Edgeworth, PA), Thornton; Daniel R. (Golden, CO) Assignee(s): Shandon, Inc. (Pittsburgh, PA) Patent Number: 5,952,239 Date filed: June 12, 1997 Abstract: There is provided a method and system for transferring biological material samples from the point of collection to a chamber for placement into a centrifuge for processing and analysis. A container is used to hold the sample from the point of collection and during transport to a sample chamber which is placed into the centrifuge. The container is provided with a threaded open end, the threads being complementary with screw threads on a lid and also with threads around a port in the chamber. Thus, the user collects the sample, places it within the container, and engages the lid to close the open end of the container. The container is transported to the laboratory, where the lid is removed, and the threads on the container engaged with the threads on the chamber to attach the container to the chamber. The container is then inverted to permit the sample to pass from the container into the chamber. The chamber may then be placed into a known centrifuge for processing. The system and apparatus are suited for the use of a curette as the tool for collecting the sample, and permit the sample-bearing curette to be conveyed in the container without contamination from the point of collection to the laboratory centrifuge. A system of notches and keys are provided to align a filter card and slide at the discharge end of the chamber and promote uniform filtering action. Excerpt(s): The invention relates to cytocentrifuge sample chambers, and more particularly to an improved cytology sample chamber with port to receive a collection bottle or container, and a method for using the same to transfer biological material from a collection tool or container to the sample chamber for analysis. Medical diagnostic processes commonly include collecting biological material specimens from patients for laboratory analysis. Biological materials subject to collection and analysis include, but are not limited to, blood, saliva, urine, epithelial smears, semen, and the like. In nearly all instances of specimen collection and analysis, it is necessary to transport the material specimen from the point of collection to the analytical laboratory, which may involve conveying the specimen a considerable distance through a large medical center complex. Occasionally, the specimen is collected in a clinic or physician's office remotely located from the laboratory, which may involve ajostling trip of hours or days from the point of collection to the point of analysis. Additionally, and particularly in the case of epithelial smears, such as pap smears, current specimen collection practices involve one or more instances of shifting the collected material from one surface or container to another surface or container. Samples of epithelial tissue commonly are retrieved from the patient's body using some type of curette, such as a specialized swab, spoon, brush, or spatula. In this disclosure, "curette" means any tool adapted for collecting epithelial and similar solid or semi-solid tissues from a patient's body. Typically, for example, a pap smear is taken using a specialized long-handled swab or brush. The delicate bristles of the brush are gently scraped or daubed across the uterine lining to collect on the bristles a sample of uterine tissue. The bristles are then wiped across a glass slide to prepare a smear for microscopic observation and other evaluation. Web site: http://www.delphion.com/details?pn=US05952239__

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Detection of dysplastic or neoplastic cells using anti-MCM5 antibodies Inventor(s): Coleman; Nicholas (Cambridge, GB), Laskey; Ronald A. (Cambridge, GB), Williams; Gareth H. (Cambridge, GB) Assignee(s): Cancer Research Campaign Technology Limited (London, GB) Patent Number: 6,303,323 Date filed: October 21, 1998 Abstract: Determination of cellular growth abnormality, particularly cancerous abnormality, by detection of target polypeptides or encoding mRNA, where the target polypeptides are members of the preinitiation complex of DNA replication in tissue, cells or fluid. Target polypeptides include CDC6, MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7. Test samples include tissue of the cervix (both biopsy and smear samples), breast, colon, lung, bladder, skin, larynx, oesophagus, bronchus, lymph nodes and urinary tract (both biopsy and cytology smear samples), in determination of cancerous and pre-cancerous cellular growth abnormality, and cells spun from urine, blood and serum, in determination of haematological malignancies and evidence of metastatic sarcoma and carcinoma. Excerpt(s): The present invention relates to assessment of cells in a sample of tissue, cells or fluid with a view to detecting cellular growth abnormality, particularly potentially (or actually) cancerous cells. Aspects of the present invention are particularly useful in screening samples such as cervical smears from women to detect those whose cervical cells are abnormal. The invention is also applicable to assessment of cells in other tissue samples, including breast, as demonstrated experimentally herein. Samples found to be abnormal may be examined in more detail and the condition of cells in the tissue investigated further. Identification of a malignant or pre-malignant condition may be followed by appropriate treatment following more extensive diagnostic procedures. The present invention is based on the surprising discovery that specific binding molecules directed against particular proteins of the preinitiation complex of DNA replication can be used to detect abnormal cells. Especially useful in the present invention are binding molecules directed against Cdc6. Also especially useful are binding molecules directed against MCM proteins, particularly MCM5. Experimental evidence included herein shows that specific binding molecules directed against Cdc6, and also those against MCM2, MCM3, MCM4, MCMS, MCM6 or MCM7 are much more effective in marking cellular growth abnormality in tissue samples than antibodies against PCNA and Ki67. A priori one would have expected Cdc6 and the MCM's to give similar results as Ki67 and PCNA, since all these proteins can be considered "proliferation markers". On cervical samples subject to antigen retrieval (pressure cooking or autoclaving), experimental results below show that in fact results obtained are similar for all these, but there is clear difference on cervical smears and frozen samples. Such samples, of primary interest for screening purposes, are not robust enough to be subject to pressure cooking. Of particular interest in the context of screening are the very strong and clear results obtained with assessment of cervical samples using anti-Cdc6 or anti-MCM binding molecules, showing high-level staining of abnormal cells, and full-thickness staining in LSIL samples. This indicates usefulness in assessment of smear samples taken from the cervical epithelial surface--and indeed this is verified experimentally herein. Full thickness staining is also seen for HSIL samples. Experimental assessment of abnormality in breast tissue, urine, blood and serum confirms generality of aspects of the present invention. Further evidence is provided by the use of the same antibodies in detection of the presence of dysplastic or neoplastic cells in body fluids by biochemical methods that can be automated. Examples demonstrated herein include detection of

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bladder cancer by analysis of urine and detection of both leukaemia and lymphoma by analysis of blood. A suitable method for such analysis is Dissociation Enhanced Lanthanide Fluorescence Immunoassay, "DELFIA". Also included is demonstration of detection of sarcoma and carcinoma cases by DELFIA on blood. Web site: http://www.delphion.com/details?pn=US06303323__ •

Endocervical sampling device Inventor(s): Colaianni; Rana A. (96 Butters Rd., Williamsport, PA 17701) Assignee(s): none reported Patent Number: 6,336,905 Date filed: October 25, 1999 Abstract: An endocervical sampling device 10 and method comprising a cytology brush 12 slidably received within a protective cylindrical sleeve 14 and having a tapered distal tip 16 protected by a penetrable seal 18. Excerpt(s): This invention is directed to a medical sampling device for use with gynecological examinations, particularly to an improved method of obtaining endocervical cell and tissue samples during colposcopy. The most widely used cervical cancer screening test is the well-known pap smear. When an abnormality is detected, further evaluation and follow up are warranted. The most common follow up test after an abnormal pap smear is colposcopy. Colposcopy is a visual inspection of the lower genital tract using a low power microscope. This test is limited to visualization of the surface of the uterine cervix, and cannot adequately detect problems within the endocervical canal. The incidence of cervical adenocarcinoma is increasing. It is estimated that up to 20% of cervical cancers occur within the cervical canal, and are not readily visible during colposcopy. Because of this significant limitation of colposcopy, the cells and tissues of the endocervical canal must be adequately sampled to allow for microscopic evaluation and accurate diagnosis. Appropriate endocervical sampling can present further diagnostic excisional (surgical) procedures in the majority of patients. There are presently several commonly used methods to sample the endocervical canal. It is estimated that the total annual cost of aggresive management is almost four billion dollars in the United States alone. One method to sample the endocervical canal is the endocervical curettage. This method employs utilizing a "curette," generally a metal instrument with sharp edges which scrape the walls of the endocervical canal. Web site: http://www.delphion.com/details?pn=US06336905__

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Environmental sample collection and membrane testing device Inventor(s): Guirguis; Raouf A. (Rockville, MD) Assignee(s): La Mina, Ltd. (Herndon, VA) Patent Number: 5,998,214 Date filed: July 15, 1997 Abstract: An apparatus for collecting fluids and holding samples taken from the fluid for qualitative and quantitative testing. The apparatus comprises a tubular container open at both ends with a quantitative test storage unit removably secured to one of said tubular container ends. The quantitative test storage unit has an open end, a cytology

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membrane mounted in the storage unit and a retaining rib. A shuttle assembly is slidably mounted in the tubular container comprising a cylindrical hollow piston defining a chamber, a thumb cover covering one end of the piston and a fluid flow aperture formed in the piston and a qualitative sample container assembly removably secured to the piston. The qualitative sample container assembly comprises a clip on membrane assembly including a membrane containing immobilized antibodies and a filter housing mounted to the clip on membrane assembly. The filter housing is adapted to be seated in the quantitative test storage unit after being slidably transported along the tubular container by the piston. Excerpt(s): The present invention is directed to an apparatus for determining the presence of microorganisms, chemicals, and other analytes in physiological, biological and environmental specimens. Thus the present invention performs diagnostic tests for pathogenic organisms, detection and identification of toxin and drug contamination in food for human and animal consumption and monitoring for pesticide residues in water, soil and food. As used in this specification the word "analyte" is a term from analytical chemistry meaning the compound for which an assay is developed (e.g., a mycotoxin, its metabolite, and toxin-DNA adducts are all different analytes that might be detected by different assays). Almost all physiological, biological and environmental fluids are composed of a liquid phase (solvent) and a non-liquid phase. The non-liquid phase consists of two main constituents: i) insoluble substance (i.e., solids and sediments) such as microorganisms, cellular debris, crystals, and particles; and ii) soluble substances (i.e., solutes) such as organic and inorganic substances. Web site: http://www.delphion.com/details?pn=US05998214__ •

Fine needle aspiration cytology device syringe holder Inventor(s): De Santis; Stephen A. (23802 Inverness Pl., Laguna Niguel, CA 92677) Assignee(s): none reported Patent Number: 5,469,860 Date filed: October 27, 1994 Abstract: A fine needle aspiration cytology device for extracting tissue samples for cytologic evaluation is disclosed. The device comprises a handle and generally Ushaped slide member with trigger attachable thereto. The handle is designed and configured to releasably engage a conventional syringe. The slide is designed to slidably engage with the handle and is provided with a slot at the base thereof for retaining the plunger of the When interconnected, the slide may move in forward or rearward positions relative the handle and further, when interconnected with a syringe, may selectively control the axial position of the plunger relative the syringe. In a preferred embodiment, the device is further provided with a manually adjustable locking detent mechanism that may releasably maintain the handle and slide in rigid connection. Excerpt(s): The present invention relates to tissue extraction devices, and particularly to hand-held devices for extracting tissue samples by fine needle aspiration. Biopsy devices for fine needle aspiration are well known to those skilled in the art. Such devices are useful for obtaining cytologic specimens for examination to confirm the diagnosis of suspected cancers. Generally, such devices are useful in sampling tissue from the breast, the head and neck, lymph nodes, and some gynecologic cancers. Other applications include lung, prostate, and other soft tissue tumor biopsies. Generally, such biopsy instruments extract samples of tissue through a small needle usually in the range of 25-

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20 gauge. A vacuum force is usually applied by a standard syringe attached to the needle, while the needle is passed several times in the tissue. A column of cells is then accumulated in the hollow channel of the needle as the needle is passed multiple times into the tumor mass. This procedure can be performed with a syringe alone or in a syringe holding device. Web site: http://www.delphion.com/details?pn=US05469860__ •

Fine needle cytology aspiration device Inventor(s): Vattuone; John R. (211 Fox Meadow Rd., Scarsdale, NY 10583) Assignee(s): none reported Patent Number: 5,655,541 Date filed: December 29, 1994 Abstract: The present invention is a fine needle cytology aspiration device having a sliding valve which allows the vacuum in the needle to be released and also the sample to be withdrawn without contamination while allowing the surgeon to use only one hand for carrying out these operations. Further, a protective sheath is described which reduces the risk of needle-stick injuries. Excerpt(s): The present invention relates to a fine needle cytology aspiration device for removing tissue and body fluid samples from a patient. In fine needle cytology aspiration it is necessary to draw body fluid and tissue samples for later analysis without allowing the samples to be contaminated with fluids or tissues from non-target locations as the needle is withdrawn. For this reason, fine needle cytology aspiration devices which allow the breaking of the vacuum in the device before the needle is withdrawn have been proposed in the prior art. U.S. Pat. No. 4,967,762, issued to DeVries, shows a fine needle aspiration device which uses a rubber O-ring to seal vents which can be used to release the vacuum in the needle. Web site: http://www.delphion.com/details?pn=US05655541__

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Inertial impact drill for cytological applications Inventor(s): Culhane; Robert L. (Manchester, NY), Fasick, III; John C. (Lima, NY), Friedrich; Edward H. (Canandaigua, NY), Henderson; David A. (Farmington, NY) Assignee(s): Burleigh Instruments, INC (Fishers, NY) Patent Number: 6,251,658 Date filed: June 14, 2000 Abstract: An inertial impact drill for diverse applications in cytology such as in-vitro fertilization, genetic research, pharmaceutical research, cloning, etc., is designed to operate in conjunction with micropipettes, microelectrodes, and micromanipulators. The drill includes two opposing actuators, one version of which is comprised a plurality of individual piezoelectric elements, the other version is comprised of a plurality of electrostrictive elements. The actuators drive a small inertial mass to produce sharp short reciprocal movements of this mass. The movements of the inertial mass result in repetitive impacts that are transferred to the micropipette or a microelectrode, which is mechanically coupled to the body of the inertial impact drill. In addition, the impacts cause mechanical oscillation of the tip of a micropipette or a microelectrode at its

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resonant frequency that is higher than the repetition rate of the impacts. The drill is suitably attached to a micromanipulator that serves to advance in a controlled mode the drill toward a cell or withdraw it from the cell. Though no net displacement of the tip of the micropipette or the electrode is produced due to the action of the drill, the tip of the micropipette or of an electrode penetrates the wall/membrane of the cell and, if appropriate, that of the nucleus. Such penetration occurs without any damage to the cell or its nucleus. The cell is held in place in the usual manner with a holding pipette. The resulting opening may then be used to inject or remove sperm or other genetic, biological, or chemical materials into the cell or the nucleus, or to insert a microelectrode. The opening in the cell wall subsequently closes. The action of the inertial impact drill is like that of a miniature jackhammer. Excerpt(s): This invention relates to an inertial impact drill, and is especially suitable for use in cytological applications, as a clinical or scientific instrument for making microscopic holes in biological tissue. It is a feature of this invention to provide an instrument that is able to puncture a cell wall with ease and enter the cell with a minimum damage thereby to preserve its viability. There is an increasing need for being able to inject into biological cells and their nuclei, genetic and other materials. Such procedures are used in cloning, in-vitro fertilization, genetic research, and in developing methods for treating cancer and genetically caused diseases. During procedures of this type a micropipette is used, guided by a micromanipulator, to penetrate the cell wall and in many cases then to enter the cell nucleus. In scientific experiments involving biological cells, microelectrodes are also frequently used to measure changes of electrical potentials or to apply electrical potentials to a cell. Web site: http://www.delphion.com/details?pn=US06251658__ •

Interactive automated cytology method incorporating both manual and automatic determinations Inventor(s): Doerrer; Rainer Hermann (Greensboro, NC), Fischer; Jochen Ernst (Elon College, NC), Knesel; Ernest Arthur (Greensboro, NC), Nguyen; Thanh Van (Palo Alto, CA) Assignee(s): Autocyte, Inc. (Elon College, NC) Patent Number: 5,677,966 Date filed: June 7, 1995 Abstract: An automated interactive cytology system provides expedited handling of samples, minimizing false negatives, while not substantially increasing the number false positives. A computerized system identifies and displays the cells which are of greatest interest to the cytologist. The system then processes this information on all cells identified to classify the slide as normal, abnormal, or questionable based on a statistical analysis of cells meeting given criteria. Before displaying the results of the statistical analysis, a cytologist reviews the cells which the computer has determined to be most significant. It is only then after the cytologist has determined whether the cells are positive, negative, or questionable, that the determination is inputted into the automated system. The automated system then compares the cytologist's analysis with its own statistical analysis. Based on the two opinions, the cytologist determines how to advise a doctor regarding the sample. Excerpt(s): The invention relates to the field of automated cytology, and in particular to an interactive system of automated cytology in which a cytotechnologist or

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cytopathologist interacts with an automated cytology screening system to markedly increase accuracy. Cytotechnologists and cytopathologists are human, and thus subject to human frailties. Among these frailties are drowsiness, inattentiveness, illness, stress, boredom, and fatigue. Moreover, current cytology practice involves a certain amount of subjectivity. By contrast, a computer is devoid of human frailties and totally objective. Accordingly, there has long been sought an automated, computerized system for cytological analysis. Presently, several computerized cytology systems are being introduced into the market place. Cytyc Corporation has been developing its CDS1000.TM. cytology workstation in which a computer system identifies cells having the highest potential for being abnormal, representative normal cells for the comparison, and clusters of cells which may be of interest to the system operator. Such a system provides the cytotechnologist or cytopathologist ("cytologist") with a narrowed field of cells for review, but generates no machine interpretation as to specimen normality or abnormality. Web site: http://www.delphion.com/details?pn=US05677966__ •

Laser scanning cytology with digital image capture Inventor(s): McCutcheon; Terry L. (Houston, TX), Reuben; James M. (Houston, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 6,656,683 Date filed: July 5, 2000 Abstract: The methods described herein are directed to subjecting a biological cell sample with multiple cell characteristics, such as DNA ploidy, immunophenotype or cellular morphology, to a laser-based interrogation with the penultimate step being creation of a digital image of the cell sample. This digital image greatly enhances the comprehensive analysis of the sample and facilitates diagnosis of the cell characteristics upon its creation in a digital format, which may also be captured in a tangible format such as a hard copy, either of which are suitable for transmission to a diagnostician, health care provider or patient. Excerpt(s): The invention relates generally to the field of cellular biology. More particularly it concerns the use of a laser scanning cytometer with a digital camera to capture an image of cells in a sample for diagnosis of cell characteristics. More specifically, it relates to diagnostics regarding cancerous cells. Pre-malignant and malignant cellular transformation is associated with changes in cell morphology and in DNA content. For early cell transformations in the absence of apparent aberrant cell morphology (a negative cytology), changes in DNA content, detected by ploidy analysis, are critical in establishing the diagnosis. DNA ploidy analysis is performed using a Laser Scanning Cytometer (LSC.TM.). The LSC is laser based technology that combines immunofluorescence, cell morphology and DNA ploidy analysis to enhance the sensitivity and specificity for detecting malignant cells. This method is capable of not only measuring DNA ploidy but identifying individual cell types based on their immunophenotype. The immunophenotype of epithelial cells from urine is determined by staining the cell cytoplasm for the presence of cytokeratin. By combining the immunophenotype with the DNA ploidy pattern, the pathologist can now identify epithelial cells that are aneuploid, a profile consistent with specific cancer cells. Previous methods using laser scanning cytology, such as described in U.S. Pat. No. 5,793,969, U.S. Pat. No. 5,885,840, U.S. Pat. No. 5,427,910 and Kawamura et al. (2000) are directed to LSC methods in which the images are visualized by a monitor display or by means of a

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CCD camera, and stored in a computer disk file. This arrangement of equipment is most useful if a cytopathologist is on-site and furthermore present during analysis to visualize the image on the monitor and make the diagnosis at that point in time. The image itself is additionally not transferable to others related to its diagnosis. Thus, a method to remove this constraint for analysis and moreover provide a tangible means to retain the data is lacking in the art. Web site: http://www.delphion.com/details?pn=US06656683__ •

Method and apparatus for checking automated optical system performance repeatability Inventor(s): Arnone; Joseph (Bainbridge Island, WA), Ortyn; William E. (Devall, WA) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,499,097 Date filed: September 19, 1994 Abstract: A test checks for appropriate positioning of priority fields for image collection and evaluation. The tests characterize lateral repeatability of stage movement in an X-Y plane, the longitudinal repeatability of the stage along a Z axis, cross coupling of motion in the Z direction from the X-Y stage movement, repeatability of the microscope objective turret positioning, mechanical centration of optical paths and the parfocality of optical paths. The process includes moving to a rough location, performing focus pans to determine the best focus and searching for a known object to register coordinate locations, processing those locations to determine the repeatability and accuracy of the motion system. Further, a means of evaluating these parameters is disclosed by which an automated cytology instrument will validate or invalidate data taken since the last position integrity check. Excerpt(s): The present invention relates to an automated method for evaluation of positioning system performance in automated machine vision instruments. More specifically, the invention provides an automated test method conducted during operation of an automated microscope system. Still more specifically, the automated test of the invention characterizes lateral repeatability of stage movement in an X-Y plane, longitudinal repeatability of the stage along a Z axis, cross coupling of motion in the Z direction from movement in the X-Y plane, repeatability of movement of a microscope objective turret, mechanical centration of optical paths, and parfocality of optical paths in an instrument performing automated analysis of biological specimens such as, for example, Pap smears. Automated analysis of biological specimens requires a high degree of repeatability and accuracy from the motion systems that position specimens in the instrument. Repeatability and accuracy errors can decrease throughput and, in the worst case, cause low prevalence data to be missed. Therefore, it is critical that motion systems employed in automated biological analysis machines perform above or beyond the engineered limits of the design. For automated biological analysis applications, such as for Pap smear analysis, repeatability of movement of a microscope slide stage in the X,Y plane, or horizontal plane, is extremely important. In such systems prioritized images may be selected under low power magnification and are relocated under high power magnification for review. In one example of an automated biological analysis system as manufactured by NeoPath, Inc. of Bellevue, Wash. a low power 4.times. field of view is divided into a 5.times.5 matrix of high power 20.times. fields. Each 4.times. subfield (or 20.times. field) is analyzed for further review. If the results dictate further inspection, the system reviews the subfield with the 20.times. magnification. Thus, stage

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repeatability becomes most critical when an object of interest in a 4.times. subfield lies near the subfield boundary. In such a case, poor XY stage repeatability may cause the high power 20.times. review to miss a suspect object. Therefore, it is one motive of the present invention to provide an X,Y repeatability test. As contemplated by the present invention, an X,Y repeatability test is conducted to verify that stage performance meets engineered limits. Web site: http://www.delphion.com/details?pn=US05499097__ •

Method and apparatus for continously monitoring and forecasting slide and specimen preparation for a biological specimen population Inventor(s): Ellison; Dayle G. (Redmond, WA), Lee; Shih-Jong J. (Bellevue, WA), Wilhelm; Paul S. (Kirkland, WA) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,625,706 Date filed: May 31, 1995 Abstract: An automated laboratory process monitoring method for a computer controlled automated cytology system initializes lab process assessment slide data so as to produce an initial batch of qualified slides. Monitor parameters are extracted from the initial batch of qualified slides so as to determine control limits. Field data is monitored by comparing the field data to the control limits. Excerpt(s): This invention relates generally to automated cytological analysis systems and, more particularly, to a method and apparatus for continuous automatic monitoring and forecasting of slide and specimen preparation quality for biological specimen fixed and stained on glass slides. Detection of disease processes is dependent on adequate specimen collection, proper fixation, staining and mounting of specimens on microscope slides. Laboratory preparation processes can vary over time because variations may occur in specimen collection, fixation, staining and mounting quality for a population of slide specimens. To ensure that slides and specimens are continuously prepared in a fashion which allows for the detection of disease processes, continuous monitoring and forecasting of slide and specimen preparation quality is required. Standards for the practice of cervical/vaginal cytology have been suggested by the introduction of the well known Bethesda System. However, significant variations in cytological specimens such as, for example, specimens stained with the well known Papanicolaou stain ("pap smears") still occur. Although the pap smear screening process can accommodate slide population, sampling, and preparation variations to some degree, variations that adversely affect the screener's ability to detect the disease process can occur. It is, therefore, important to develop a monitoring process to detect and forecast such variations in order to maintain adequate laboratory preparation for the detection of disease process. Web site: http://www.delphion.com/details?pn=US05625706__

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Method and apparatus for detection of unsuitable conditions for automated cytology scoring Inventor(s): Lee; Shih-Jong J. (Bellevue, WA), Wilhelm; Paul S. (Kirkland, WA) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,715,327 Date filed: September 20, 1994 Abstract: A method and apparatus for determining whether a slide is suitable for processing. A suite of suitability tests are performed by an automated microscope system. The tests include magnification error flags, staining flags, main optical density flags, including detected intermediate cell nuclei, rings around detected intermediate cell nuclei, average texture measure of detected intermediate cell nuclei, average contrast to detected intermediate cell nuclei to cytoplasm, standard deviation of detected intermediate cell nuclei optical densities, detected intermediate cell ratios, average stripe area, measure of a saturated magnification of the image, measure of a grossly saturated magnification, and the percentage of images focused properly on a first try, including images never focused properly. The automated microscope quantifies the measurements in a reliable and repeatable way. Excerpt(s): The invention relates to a slide suitability scoring apparatus and, more particularly, to a slide suitability scoring apparatus for an automated cytology system. A slide suitability score results from analyses applied to measurements of a slide's characteristics and an automated cytology system's effectiveness. Slide characteristics are properties of the biological sample on the slide and the slide itself such as bubble area, coverslip and mounting medium thickness, and staining properties. Automated cytology systems that score biological slides have an associated slide scoring effectiveness. Machine effectiveness measures, such as the percentage of requested fields of view that were focused adequately or the percentage of acquired images that had saturated pixels, are measures of how well the automated cytology system has begun to process a slide and how it proceeds to process a slide. For a particular slide, the slide suitability score determines the reliability of other types of slide scores, and thus, whether those scores should be reported. If a particular slide is anomalous, or if the automated cytology system did not operate effectively on the slide, it would be desirable to flag the unacceptable machine condition or slide characteristic so that potentially false results are not used. The invention provides a method and apparatus for determining whether a slide is suitable for processing. The invention provides a suite of suitability tests that are performed by an automated microscope system. The tests include machine processing error flags, staining measures including mean detected intermediate cell nuclei stain, mean detected intermediate cell cytoplasm stain, mean texture of detected intermediate cell nuclei, mean contrast between detected intermediate cell nuclei and cytoplasm and standard deviation of detected intermediate cell nuclear stain, optical density, detected intermediate cell ratios, average stripe modulation patterns area, counts of saturated pixels within the images, the percentage of images focused properly on a first try, and the percentage of images never focused properly. The invention provides an apparatus to quantify these measurements in a reliable and repeatable way. Web site: http://www.delphion.com/details?pn=US05715327__

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Method and apparatus for obtaining a cytology monolayer Inventor(s): Guirguis; Raouf A. (11836 Dinwiddie Dr., Rockville, MD 20852) Assignee(s): none reported Patent Number: 5,471,994 Date filed: December 23, 1993 Abstract: The present invention is directed toward a cytology collection apparatus and a method for preparing a uniform monolayer of cells. The apparatus allows the rapid preparation from body fluids of a cytology monolayer with very few overlapping cells and with fewer contaminants than prior devices. The apparatus is in the form of an openable cell collection container which houses a filter for collection of cells when body fluid passes therethrough. Excerpt(s): The present invention is directed to an apparatus and method for collecting a uniform layer of cells from body fluids suitable for use in cytological protocols. Diagnostic cytology, particularly in the area of clinical pathology, bases diagnoses on a microscopic examination of cells and other biological samples. The accuracy of a diagnosis and the preparation of optimally interpretable specimen slides may depend both upon adequate patient sampling and on culture or slide preparation procedures. Prompt processing of urine to obtain fresh cells traditionally has been recommended to ensure the accuracy of quantitative culture results, urinalysis and microscopy. Fresh cells tend to stick to a glass slide much better than cells from preserved urine, allowing for smoother cell spread onto the glass body. Delays in processing, negligent care in either inpatient or outpatient settings and lack of refrigeration may lead to non-optimal slide preparation. One known solution to the delay problem is the use of chemical preservatives with the urine. The presence of liquid preservatives, however, in the urine specimen raises the specific gravity of the specimen to unmeasurable levels and may limit the potential usefulness of the urine for various types of traditional quantitative analysis, such as slide microscopy. Web site: http://www.delphion.com/details?pn=US05471994__

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Method for cytological system dynamic normalization Inventor(s): Frost; Keith L. (Seattle, WA), Lee; Shih-Jong J. (Bellevue, WA), Nelson; Alan C. (Redmond, WA), Nelson; Larry A. (Bellevue, WA), Youngmann; Carl E. (Seattle, WA) Assignee(s): NeoPath, Inc. (Redmond, WA) Patent Number: 5,627,908 Date filed: September 20, 1994 Abstract: A cytological system dynamic normalization of a normal threshold. An analysis score from a slide is compared against a threshold to determine whether or not the slide is normal or requires microscopy review. The normal threshold is dynamically adjusted using a three step process. The process is implemented on an automatic cytology system. The first step is initial calibration of the system to determine an initial threshold. The second step is a running adjustment of the normal threshold in response to the presentation of new slides to the automatic cytology system. The third step is the batch certification of every slide. The threshold may be adjusted for an analysis score, a quality control score, or a screening score.

Patents 131

Excerpt(s): This invention relates to a cytological specimen classifier, more particularly to a method for dynamically normalizing decision variations concerning biological specimens. Conventional Pap smears prepared in accordance with Papanicolaou staining procedures have characteristics that vary a great deal from smear to smear. Some of these variations are caused by patient population differences. As an example, labs having slides from sexually transmitted disease clinics will normally have a higher percentage of abnormal slides. A normal slide from this population may have a higher occurrence of benign cellular change or inflammatory conditions. Other significant sources of variations are specimen sampling and preparation. Also, the Papanicolaou staining procedure may be subject to a wide variety of variations in staining recipe, staining material, staining batches, etc. These preparation variations are found as interlab differences as well as intra-lab staining batch differences. Machines that automate or semi-automate cervical smear screening typically generate an analysis score for each screened slide. The higher the analysis score, the more likely the slide is from a patient with an abnormality. The score is sensitive to the above variations. Normal slides with darker cell staining are more likely to have higher analysis scores. An automated cervical smear screening system with a fixed analysis score threshold typically yields different performance operating points, such as normal slide specificity and abnormal slide sensitivity, for slides from different labs or different batches from the same lab. Such inconsistencies lead to inconsistent classification results. Web site: http://www.delphion.com/details?pn=US05627908__ •

Method of distributing material onto a microscope slide of a large cytology sample chamber Inventor(s): Hayes; William J. (Edgeworth, PA) Assignee(s): Shandon, Inc. (Pittsburg, PA) Patent Number: 5,589,400 Date filed: August 18, 1995 Abstract: The method of distributing biological material suspended in a liquid sample comprises the steps of directing the liquid sample into a centrifuge sample chamber along a tortuous path of vertically spaced surfaces in the chamber, each of the surfaces being in communication with a discharge opening from the chamber to one surface of the microscope slide, continuing to direct the sample into the chamber until some of the biological material is deposited on portions of at least one of the surfaces and centrifuging the sample chamber whereby the biological material on each of the surfaces of the chamber passes through the discharge opening on the one surface of the slide. Excerpt(s): This invention generally relates to cytocentrifuge sample chambers and more particularly to a novel and improved cytology chamber and method for distributing biological material on a microscope slide during the centrifugation of body fluid samples. Cytocentrifuges are small, precision centrifuges which are particularly designed for centrifuging blood and other body fluid samples in order to separate these fluids into various components. These machines are typically used to deposit sediment materials such as cellular structures onto the surface of a microscope slide for further detailed microscopic study. A cytocentrifuge has a removable head typically containing an even number of sample chamber assemblies in a carrier and spaced symmetrically about the centrifuge axis. The head has a removable top and an annular bowl shaped bottom. The bottom of the head supports the carrier which positions the chamber assemblies symmetrically around the inside of the annular bowl. When the top is

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installed on the bottom, all of the sample chamber assemblies are completely sealed inside. The assembled head is then installed in the cytocentrifuge for the centrifugal operation. Web site: http://www.delphion.com/details?pn=US05589400__ •

Mucosal sampler Inventor(s): Fowler; Robert Stuart (Scottsdale, AZ) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,607,494 Date filed: January 19, 2001 Abstract: A cytology cell sampler for use in collecting mucosal cell samples from a human comprising a handle and a head portion. The handle is grasped by the operator and the head portion is then abutted a patient's mucosal surface for sample collection. The head portion has a first plate and a plurality of secondary plates with the first plate attached to the handle opposite the end grasped by the operator. The first plate has a longitudinal axis generally along a longitudinal axis of the handle, and the plurality of secondary plates project from the first plate generally perpendicular to the longitudinal axis of the first plate. There is at least one collection space between the plurality of secondary plates. Each secondary plate has a shaped free edge for contacting the mucosal surface of the human, collecting a sample between the plurality of secondary plates by scraping the mucosal surface with the shaped free edges. Excerpt(s): The present invention discloses a device for mucosal cell and tissue collection, in particular, for an improved device for performing cytological smears and endocervical curettage useful in the detection and diagnosis of cancer, and more particular, an improved device for collecting cytological smears and endocervical tissue for the detection of uterine cervical dysplasia and cancer. Uterine cervical cancer poses a significant medical risk in the female population. The commonest test for screening a patient for cervical dysplasia or cancer of the cervix consists of obtaining a sample of endocervical and ectocervical cells lining the cervix and performing the Papanicalaou test on the sample, the so called Pap test. A complimentary test, known as the endocervical curettage is used to collect endocervical tissue for pathological analysis. In its own right, the Pap test is fairly simple to perform and reasonably sensitive in providing accurate and reliable results. A recent advancement has improved the quality of cellular deposit by immersion of samplers into cytology fluid and processing by a monolayer technique. Difficulty persists in achieving an adequate collection and deposition of cells into the cytology fluid for processing and analysis. The traditional method uses a shaped wood spatula, the shaped edge being scraped over the mucosal surface, for example, the mucosa of the ectocervix and opening of the endocervical canal. Unfortunately, this method commonly results in a specimen lacking endocervical cells and occasionally insufficient squamous cells, as well. Web site: http://www.delphion.com/details?pn=US06607494__

Patents 133

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Multi-lumen endoscopic catheter Inventor(s): Holsinger; Damond C. (New Holland, PA), Jacob; Harold (Lawrence, NY), Leighton; David F. (West Lawn, PA), Weaver; George W. (East Earl, PA) Assignee(s): Arrow Precision Products, Inc. (Reading, PA) Patent Number: 5,599,299 Date filed: January 31, 1994 Abstract: Multi-lumen catheters are intended for advancement through the accessory channel on endoscope into a body passage into the gastrointestinal system. The catheters have two or more independent lumens extending continuously to ports at the distal tip for injection of a contrast medium simultaneously with a guide wire for ERCP procedures and for passage of accessories such as visualization devices, polypectomy snares, cytology brushes, papillotomes and stone baskets for catheterization, diagnosis and treatment within the biliary tract. Use of balloons for maintaining a catheter in fixed position in the biliary tract and for dilatation is also disclosed. The catheters employed are extrusions of a resin comprised of nylon and PEBA. The catheters may also be extruded from polyurethane. Multi-lumen catheters having a reduced diameter distal tip portion on which a dilatation balloon is located are also disclosed. The reduced diameter distal tip portion may serve as a platform for support of a stent. Excerpt(s): The present invention is directed to catheters adapted for passage through the accessory channel of an endoscope into a duct or passageway within the gastrointestinal system of the body. Although not limited in its applicability and scope, the invention has particular applicability to procedures which involve the advancement of the catheter to positions within the biliary tract and especially to the practice of Endoscopic Retrograde Cholangiopancreatography. A number of procedures have evolved in recent years using instruments intended to be inserted through an endoscope in various positions within the gastrointestinal system for the purpose of diagnosis and for therapeutic procedures, including the insertion of stents, devices for the extraction of stones from the biliary duct, the removal of polyps and the extraction of tissue for biopsy purposes. One diagnostic technique which has come into use is Endoscopic Retrograde Cholangiopancreatography (ERCP) which is described in copending application Ser. No. 07/880,842, filed May 11, 1992. The ERCP technique is an endoscopic technique which involves the placement of a side-viewing instrument within the descending duodenum. The procedure eliminates the need for invasive surgical procedures for identifying biliary stones and other obstructions of the biliary and pancreatic ducts. As background of the invention, the ERCP technique exemplified the problems and difficulties which the present invention addresses. Web site: http://www.delphion.com/details?pn=US05599299__

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Optical device bearing a pattern for representing at least one image that is capable of having microscopic detail Inventor(s): Morton; Steven G. (39 Old Good Hill Rd., Oxford, CT 06478) Assignee(s): none reported Patent Number: 5,567,573 Date filed: April 3, 1995

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Abstract: A method for manufacturing ultra high resolution images, especially transmissive images, is described that is capable of fabricating images where each pixture element (pixel) has an intrinsic gray-scale, the gray-scale has a wide dynamic range, there are no voids between pixels, fabrication is not limited by the wavelength of light, and the pixels can be so tiny that their appearance is diffraction-limited. As a result, life-size images of cytology specimens can be fabricated with sufficient spatial and shading detail to show the details of the cell nuclei, and high-density, non-volatile, optical memory devices can be made. The method applies the tools of the semiconductor and optical device fabrication industries, and places registration marks on a substrate, repetitively: (1) masks the substrate, (2) places a layer of thin film upon the masked substrate, precisely registering each mask with the registration marks on the substrate, and (3) removes the mask and removes the thin film that did not land on the substrate or upon previously deposited thin film; where: (1) the optical transmission of the thin film varies from one layer to the next and is chosen from a set of transmission values, (2) the optical transmission of a given pixel is the composite of zero, one or a few thin film layers, (3) some of the thin film layers are used to form many of the pixels and some are not, and (4) the set of thin film optical transmissions is chosen in such a fashion as to give many shades while using a small number of manufacturing steps. Excerpt(s): This invention relates generally to the fabrication of permanent images upon a substrate, particularly where one desires to have extremely high spatial resolution and to create shaded images that are very small. Such small, high resolution images can be used to create optical memories or the life-size images of cytology specimens where one desires to resolve the shapes and contents of the cell nuclei in the life-size images created. The invention was motivated by a series of articles in national newspapers including The New York Times and The Wall Street Journal in the mid 1980's about the difficulties of adequately screening millions of cervical Pap smears every year, resulting in the deaths of many women from cervical cancer. Others have responded to these same articles by developing automated Pap smear screening systems. Law makers have responded to these articles by mandating that the quality of the work performed by cytotechnicians in cytology screening laboratories should be assured. As the performance of automated Pap smear screening systems improves and their use becomes widespread as a means of cost containment, it becomes increasingly important to periodically confirm that the machines are doing a good job. Periodic checking, rather than verification only at the time of machine type acceptance by the medical community, is necessary because the image processing algorithms will be updated over time and because the machines have many operational variables that affect their performance. An image digitization system as simple as a facsimile machine cannot produce the same digitized image twice, and a Pap smear screening system is far more complex, having to recognize the complex images it digitizes. Web site: http://www.delphion.com/details?pn=US05567573__ •

Slide dispensing device and method Inventor(s): Leopando; Mark E. (545 E. Cypress Ave., Unit E, Burbank, CA 91501) Assignee(s): none reported Patent Number: 5,494,828 Date filed: July 13, 1994 Abstract: A slide dispensing device is described which has a cone shaped upper portion which is nestable to a conventional cytology pipette, and a lower portion which is fan

Patents 135

shaped ending in a long narrow dispensing slot to evenly distribute a specimen material onto a slide. A method is described in which a prepared specimen is aspirated into a pipette; then the pipette is nested to a slide dispensing device which has an upper portion which is nestable to the pipette and a fan shaped lower portion forming a long narrow dispensing slot; then the assembly is placed so that the long narrow dispensing portion is on a slide; and the assembly is moved along the slide while the pipette is squeezed to expel the specimen in an even band on the slide. Excerpt(s): The present invention relates to the field of laboratory slide preparation. In particular it relates to cytology slide preparation. Also the fields of slide preparation for microbiology, hematology, special stains, and cytogenetics are contemplated. The task of depositing a specimen on a slide for cytological examination has been the subject of some attention. It is desired to deposit the specimen spread thinly and evenly and in the case of some types of specimens, in a monolayer. There has been considerable effort to improve cytology smear presentation. One aspect concentrates on the monolayered presentation of cells on the slide. Web site: http://www.delphion.com/details?pn=US05494828__ •

Tissue removing device Inventor(s): Dostal; Daniel (Eden Prairie, MN), Lind; Stuart (Minneapolis, MN), Skaaland; John (Hopkins, MN) Assignee(s): Annex Medical, Inc. (Eden Prairie, MN) Patent Number: 5,722,423 Date filed: December 30, 1994 Abstract: A tissue removing device and brush construction, and more particularly, a cytology brush construction which is intended to be utilized in conjunction with a specimen sampling device for the collection of microbiological biopsy specimen from a body cavity. The brush construction is attained by the provision of at least one initially flat element which may have at least one or opposing longitudinal outer edges in either a wavy-linear configuration, rectilinear form, or which may incorporate a multiplicity of closely spaced, parallel slits cut in from at least one longitudinal edge so as to leave a central longitudinal connecting web in the element. The flat element, upon being twisted into a helical configuration or by being interposed between a pair of wires or superimposed wire strands and which are then twisted, will exhibit the desired configuration and properties of a tissue removing device or cytology brush, with the elimination of the multiplicity of separate discrete bristles or filaments heretofore employed. Also disclosed as a brush structure is the use of a flattened plastic tube or the like having a plurality of slits cut into it from both edges thereof and which, upon being deformed into a helical brush-shape, will provide for an improved and enhanced collection of tissue specimen material. Excerpt(s): The present invention relates to a tissue removing device, and more particularly, pertains to a tissue removing scraper, rasp or cytology brush construction which is intended to be utilized in conjunction with a specimen sampling device for the collection of microbiological biopsy or tissue specimen from a body cavity. Moreover, the tissue removing device or cytology brush is especially adapted for, but not limited to, the brushing and retrieving of microbiological biopsy and tissue specimen from areas of the pulmonary or gastrointestinal tracts of a patient which are ordinarily difficult to reach. Other applications may include utilization for cardiovascular plaque removal;

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uses in urology, obstetrics/gynecology, neurological; and even in connection with the employment of the inventive device as endoscope cleaning brushes. The tissue removing device can also be conceptually utilized in various industrial aspects, such as for the cleaning/treatment of delicate tools and instruments. Pursuant to a specific aspect of the invention, the cytology brush construction is of a simple and inexpensive, yet sturdy and reliably operable nature, and is constituted from a minimum number of components which will avoid encountering any loss of brush bristles during use in the implementation of invasive biopsy procedures, while concurrently enhancing the versatility and range of applicability of the cytology brush. The inexpensive and simple construction of the cytology brush also renders the latter readily disposable in a highly economical manner after only a single use. Biopsy specimen sampling and tissue removing devices employing cytology brushes for the collecting of microbiological specimen from body cavities are extensively employed in the medical technology, particularly in conjunction with their use in endoscopic procedures, and are of widely varied types which, however, are concurrently either of generally complicated constructions necessitating the manufacture and assembly of cytology brushes or similar structures consisting of numerous generally expensively produced components or; alternatively, may be of such simple constructions as to lack the sophistication and strength to enable them to be satisfactorily applied for their intended purposes. This, in particular, pertains to the various types of cytology brushes currently employed for the collection of microbiological biopsy specimen from the body cavities of patients through the insertion of the brushes into endoscopes and in the brushing and obtention of microbiological biopsy samples from pulmonary or gastrointestinal tracts, and other potentially biopsied regions of the body cavities from which tissues are to be obtained. In general, presently utilized cytology brushes, which are utilized for the obtaining of microbiological biopsy specimen, incorporate a flexible operating cable or wire which is actuated from a first or proximal end in order to effectuate longitudinal and rotational movement of the wire within a flexible sheath, for instance, such as a sheath constituted from plastic tubing which is insertable into the biopsy channel of an endoscope, and at the end of the sheath extending into the body cavity of a patient has a second or distal end of the wire equipped with a cytology brush structure. Ordinarily, such a cytology brush includes a multiplicity of discrete or separate bristles, each generally constituted from nylon or suitable substantially rigid but resiliently flexible plastic material, wherein the radially outer ends of the bristles, when the cytology brush is extended outwardly beyond a distal end of the sheath into the body cavity, are adapted to brush against and obtain microbiological biopsy specimen from specified areas or regions in the body cavity of the patient. Thereafter, the cytology brush with the microbiological biopsy specimen entrained in or located on the bristles is withdrawn from the distal end of the plastic sheath, and the entire sampling device retracted from the body cavity through the endoscope. Although this type of brush construction is generally satisfactory in enabling the cytology brush bristles to contact the particular internal body portions or organs being biopsied and from which the microbiological biopsy specimen or tissue samples are to be obtained, the structure of the brush bristles being constituted from a multiplicity of separate components which are clampingly retained in a helically-coiled position between twisted strands of the flexible wire, raises the concern of the possibility that some of the bristles may become loosened and detached while in the body cavity of the patient, and resultingly leading to potential physical hazards and infection to the patient, and attendant legal liability to the medical practitioner and facility. Web site: http://www.delphion.com/details?pn=US05722423__

Patents 137

Patent Applications on Cytology As of December 2000, U.S. patent applications are open to public viewing.5 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to cytology: •

Automated scanning method for pathology samples Inventor(s): Bonnet, Jan; (Leiden, NL), Gregson, Mark; (Hexham, GB), Mesker, Wilhelmina E.; (Noordwijk, NL), O'Kelly, Padraig S.; (Wylam, GB), Shields, Kevin; (Tyne ?amp; Wear, GB), Sloos, Willem C.R.; (Hazerswoude-dorp, NL), Tanke, Hendrikus J.; (Rijnsburg, NL), Verwoerd, Nico Peter; (Hazerswoude-Rijndijk, NL), Vrolijk, Johannes; (Rijnsburg, NL) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030012420 Date filed: June 6, 2002 Abstract: Scanning and analysis of cytology and histology samples uses a flatbed scanner to capture images of the structures of interest such as tumor cells in a manner that results in sufficient image resolution to allow for the analysis of such common pathology staining techniques as ICC (immunocytochemistry), IHC (immunohistochemistry) or in situ hybridization. Very large volumes of such material are scanned in order to identify cells or clusters of cells which are positive or warrant more detailed examination, and if analysis at higher resolution is necessary, information regarding these positive events is transferred to a secondary microscope, such as a conventional scanning microscope, to allow further analysis and review of the selected regions of the slide containing the sample. Excerpt(s): This invention relates generally to the automated analysis of samples (specimens) such as biological samples having microscopic features, and more specifically to the use of a flatbed scanner in such analysis. The desirability of analyzing lymph nodes of cancer patients for micrometastatic (tumor) cells is well established, both as a indicator of patient prognosis and as a possible guide as to the advisability of treatment with adjuvant therapy (chemotherapy/hormones). Unfortunately, current practice makes it impractical to examine an entire lymph node. Typically, a lymph node is on the order of 5 mm in length. In routine pathology this node is cut in two and embedded in paraffin. This results in two (half) nodes embedded next to each other with a depth on the order of 2.5 mm. The current practice is to take sections of this material, stained with hematoxylin and eosin (H&E) which are then examined manually by a pathologist using a conventional microscope. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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This has been a common practice outside the United States prior to December 2000.

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Barrett's esophagus cytology device Inventor(s): Secrest, Dean J.; (Concord, OH), Younker, Marlin; (Waite Hill, OH) Correspondence: William Johnston; Watts Hoffmann Fisher & Heinke CO; PO Box 99839; Cleveland; OH; 44199-0839; US Patent Application Number: 20030208134 Date filed: November 6, 2002 Abstract: A method and apparatus for obtaining esophageal cells for diagnostic purposes comprises inserting the distal end of a flexible support body in a patient's stomach via the esophagus and mouth so that the proximal support body end projects from the mouth. A balloon at the distal support body end is inflated and the support body is withdrawn until the inflated balloon engages the sphincter at the stomach entrance. A support body location is marked that is a predetermined distance from the patient's dental arch when the inflated balloon engages the sphincter at the stomach entrance. The balloon is deflated and the support body is withdrawn so that the marked locatin is adjacent the patient's dental arch. The support body is withdrawn a second predetermined distance and a second support body location, adjacent the patient's dental arch, is marked. A cell collecting element is deployed from within the distal end of the support body so that the cell collecting element is disposed in the esophagus within the predetermined distance from the sphincter. The support body is reciprocated through the second predetermined distance with the cell collecting element deployed so that cells from the esophagus within the second predetermined distance from the sphincter are deposited on the cell collecting element. The cell collecting element is retracted into the body so that it does not engage the esophagus wall, and the body is withdrawn from the patient. Excerpt(s): The present invention relates to collecting cells for cytological examination and more particularly to a method and device for collecting Barrett's esophagus cells for cytological study. Barrett's esophagus is a condition in which cells lining the esophagus near the entrance to the stomach become abnormal due to exposure to stomach acid. Barrett's esophagus typically extends about 8 cm away from the stomach entrance. The condition is often a precursor of esophageal cancer, so detection of abnormal cells indicating not only esophageal cancer, but also Barrett's esophagus, is important. Barrett's esophagus and esophageal cancer are diagnosed by visually inspecting the esophagus lining, collecting cells from the esophagus lining and subjecting them to cytological examination. Procedures for collecting the cells have been such that diagnosing Barrett's esophagus or esophageal cancer was quite expensive. When the esophagus lining was visually inspected, an endoscope was employed and the patient was anesthetized for the process. The visualization process enables the physician to determine the location of the cells in question. A cell collection device may then be inserted through the endoscope and engaged with the esophagus lining in the areas where the cells in question have been located. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 139

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Cell collection apparatus Inventor(s): Auerbach, Peter; (Groton, CT), Auerbach, Robert D.; (Madison, CT), Barenboym, Michael; (Ashland, MA) Correspondence: Neal L. Rosenberg, ESQ.; Amster, Rothstein & Ebenstein; 90 Park Avenue; New York; NY; 10016; US Patent Application Number: 20030109804 Date filed: December 11, 2001 Abstract: A collection container for containing a solution useful for retrieval of cell samples both from a spatula having a collector with ectocervical cell samples thereon and from a cytology brush having bristles with endocervical cell samples thereon. Excerpt(s): The present invention relates to a collection apparatus for containing a solution useful for retrieval of cell samples, and more particularly, to such apparatus for retrieving cervical cell samples both from a spatula having a collector and from a cytology brush having bristles. U.S. Pat. No. 5,422,273 discloses a cell collection apparatus which utilizes a combination of fins for agitating the bristles of a cytology brush within a fixative solution, thereby permitting retrieval of the cell samples from the cytology brush. While the apparatus is said to be useful in the collection of cell samples from cytology brushes having different configurations, the disclosed apparatus has utility only in the collection of endocervical cells--that is, the cells removed from within the interior of the cervix by a cytology brush. Current medical standards require that the Papanicolaou ("Pap") test be performed on a collection of both endocervical cell samples and ectocervical cell samples. While endocervical cells are found in the interior of the cervix and removed therefrom by a cytology brush having on a leading end thereof bristles which are inserted into the interior of the cervix, endocervical cells are found on the exterior of the cervix and are removed therefrom with a spatula having on a leading end thereof a collector (rather than bristles) for scraping endocervical cells from the exterior of the cervix. For a variety of different reasons including inter alia the central location of the cell removal member within the container of the disclosed apparatus, the conically shaped closed end of the disclosed apparatus, and the presence of an alignment member at the open end of the container of the disclosed apparatus, the disclosed apparatus is simply not suited for the removal of ectocervical cell samples from the spatula typically used to collect such ectocervical cell samples from the exterior of the cervix. The aforementioned features of the disclosed apparatus limit the ability of the spatula to be moved within the solution and, in particular, to be struck against an abutment surface with sufficient force to dislodge the ectocervical cell samples therefrom into the solution. Further, the disposition of the cell removal member totally within the solution placed in the container (so that the solution covers the top of the cell removal member) and the presence of the alignment member at the top of the container interfere with visualization of the cell removal member, thereby rendering use of the apparatus difficult. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cervical cytology instrument Inventor(s): Kobren, Myles S.; (Woodbury, NY), Menzin, Andrew W.; (Roslyn Heights, NY) Correspondence: Eliot S. Gerber; Fay, Kaplun & Marcin Llp; 100 Maiden Lane; New York; NY; 10038; US Patent Application Number: 20020068881 Date filed: December 4, 2000 Abstract: A gynecological instrument for collecting cell samples from the endocervix and exocervix and exocervix, e.g., a Pap Smear brush, has a handle portion carrying a brush base. The brush is connected to the brush base and comprises a central portion of stiff bristles which are generally perpendicular to the handle axis, and a line of softer bristles generally aligned with that axis. Excerpt(s): The present invention relates to medical devices and more particularly to gynecological instruments for collecting cell samples from the endocervix and exocervix, e.g., "Pap Smear" brushes. At the present time, the "Pap smear" (Papanicolou Smear) is one of the most important procedures in gynecology and one of the most effective cancer screening tests in history. It is non-invasive and without risk and provides many benefits to patients. If the cells are adequately collected and correctly analyzed, the Pap smear can detect cancers and pre-cancers of the lower genital wall, i.e., cancer of the cervix. This has been demonstrated to have led to a marked reduction in the incidence of cervical cancer and improved survival, which occurs because the cancers are caught early. Other treatable medical conditions may also be detected on a Pap smear. New technology has also allowed the coupling of other important medical tests (such as STD testing) to the material obtained for Pap smear examination. Various devices are commonly used to obtain a Pap smear. For example, a cotton swab at the end of a stick may be used to obtain cells from the outer surface of the cervix, that type of device being called a cervical swab smear. Another device, to obtain cells from the surface of the cervix (exocervical or ectocervical) and from the endocervix (cervical canal), is a wooden or plastic spatula (stick) having a flat broad edge and two lobes. However, such a spatula may not obtain a sufficient amount of vaginal wall cells. To obtain endocervical cells, it is common to use an endocervical aspirator or an endocervical brush having bristles at the end of a metal wire, like a pipe-cleaner brush. In addition, a widely used device to obtain both types of cells is a plastic brush called a "Pap broom" or a "Papette" (TM of Wallach Surgical Devices) having elongated vertical plastic bristles arranged in a fan shape. Such devices may, though, not penetrate the endocervical canal and retrieve sufficient endocervical cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Detection of abnormal cells Inventor(s): Adehl, Didier; (Chicago, FR), Domanik, Richard A.; (Libertyville, IL), Gombrich, Matthew; (Chicago, IL), Gombrich, Peter P.; (Chicago, IL), Kawaguchi, Jennifer; (Chicago, IL), Keesee, Susan; (Chicago, IL), Kusswurm, Dan; (Chicago, IL) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20040002125 Date filed: November 14, 2002

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Abstract: Cellular samples such as cervical cells can be analyzed using a unique combination of markers that identify abnormal cells while subtracting out false positives that would otherwise be generated by, for example, normally proliferating cells and non-cellular debris. Dysplastic cervical cells can thus be identified quickly and accurately. An assay including analytical reagents and methods of their use can be employed in classifying cervical cytology specimens as being normal or abnormal. This assay is configured to be performed using any of several commonly available classes of laboratory instrumentation and upon the entire range of cervical cytology specimen preparations encountered in clinical practice. This assay is particularly intended for use in high volume screening environments, but also has both diagnostic and research applications. Excerpt(s): This application is related to and claims priority to Serial No. 60/280,239, filed Mar. 30,2001, entitled "DETECTION AND DIFFERENTIATION OF CANCEROUS CELLS", and Serial No. 60/280,216, filed Mar. 30, 2001, entitled "MARKER COCKTAIL AND USE IN IDENTIFYING CERVICAL CELL ABNORMALITIES", which applications are specifically incorporated by reference herein. The invention relates generally to analyzing cellular material and relates more specifically to analyzing cervical cells. In particular, the invention relaters to techniques for detecting cervical abnormalities. More particularly, the invention relates to a process whereby cervical cellular samples can be rapidly evaluated for the presence of cellular abnormalities that are indicative of cancerous or precancerous states. Cervical cancer is the second most common form of cancer among women and can be caused by common papilloma viruses that can be spread through sexual contact. In the United States alone, there are believed to be more than 2,000,000 cases each year of precancerous cervical abnormalities, 65,000 cases of cervical carcinoma in situ, and 15,800 cases of invasive cervical cancer. Outside the U.S., where screening is less common, there are more than 450,000 cases of cervical cancer each year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Detection of dysplastic or neoplastic cells using anti-MCM2 antibodies Inventor(s): Coleman, Nicholas; (Cambridge, GB), Laskey, Ronald A.; (Cambridge, GB), Williams, Gareth H.; (Cambridge, GB) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20030143646 Date filed: August 7, 2001 Abstract: Determination of cellular growth abnormality, particularly cancerous abnormality, by detection of target polypeptides or encoding mRNA, where the target polypeptides are members of the preinitiation complex of DNA replication in tissue, cells or fluid. Target polypeptides include CDC6, MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7. Test samples include tissue of the cervix (both biopsy and smear samples), breast, colon, lung, bladder, skin, larynx, oesophagus, bronchus, lymph nodes and urinary tract (both biopsy and cytology smear samples), in determination of cancerous and precancerous cellular growth abnormality, and cells spun from urine, blood and serum, in determination of haematological malignancies and evidence of metastatic sarcoma and carcinoma.

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Excerpt(s): The present invention relates to assessment of cells in a sample of tissue, cells or fluid with a view to detecting cellular growth abnormality, particularly potentially (or actually) cancerous cells. Aspects of the present invention are particularly useful in screening samples such as cervical smears from women to detect those whose cervical cells are abnormal. The invention is also applicable to assessment of cells in other tissue samples, including breast, as demonstrated experimentally herein. Samples found to be abnormal may be examined in more detail and the condition of cells in the tissue investigated further. Identification of a malignant or pre-malignant condition may be followed by appropriate treatment following more extensive diagnostic procedures. The present invention is based on the surprising discovery that specific binding molecules directed against particular proteins of the preinitiation complex of DNA replication can be used to detect abnormal cells. Especially useful in the present invention are binding molecules directed against Cdc6. Also especially useful are binding molecules directed against MCM proteins, particularly MCM5. Experimental evidence included herein shows that specific binding molecules directed against Cdc6, and also those against MCM2, MCM3, MCM4, MCM5, MCM6 or MCM7 are much more effective in marking cellular growth abnormality in tissue samples than antibodies against PCNA and Ki67. A priori one would have expected Cdc6 and the MCM's to give similar results as Ki67 and PCNA, since all these proteins can be considered "proliferation markers". On cervical samples subject to antigen retrieval (pressure cooking or autoclaving), experimental results below show that in fact results obtained are similar for all these, but there is clear difference on cervical smears and frozen samples. Such samples, of primary interest for screening purposes, are not robust enough to be subject to pressure cooking. Of particular interest in the context of screening are the very strong and clear results obtained with assessment of cervical samples using anti-Cdc6 or anti-MCM binding molecules, showing high-level staining of abnormal cells, and full-thickness staining in LSIL samples. This indicates usefulness in assessment of smear samples taken from the cervical epithelial surface--and indeed this is verified experimentally herein. Full thickness staining is also seen for HSIL samples. Experimental assessment of abnormality in breast tissue, urine, blood and serum confirms generality of aspects of the present invention. Further evidence is provided by the use of the same antibodies in detection of the presence of dysplastic or neoplastic cells in body fluids by biochemical methods that can be automated. Examples demonstrated herein include detection of bladder cancer by analysis of urine and detection of both leukaemia and lymphoma by analysis of blood. A suitable method for such analysis is Dissociation Enhanced Lanthanide Fluorescence Immunoassay, "DELFIA". Also included is demonstration of detection of sarcoma and carcinoma cases by DELFIA on blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Device and method for cytology slide preparation Inventor(s): Dores, Gerson Botacini das; (Sao Paulo, BR), Lazar, James G.; (Bethesda, MD), Mielzynska-Lohnas, Iwona; (Mt. Airy, MD), Payne, William J.; (Brookville, MD), Slattery, Joseph P.; (Poolesville, MD), Taromaru, Eliane; (Sao Paulo, BR) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20020039796 Date filed: April 4, 2001

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Abstract: This invention provides a novel device and method for preparing cytology slides. The device comprises a book-like form including an absorbent material and filter attached to the inside surface of a front cover and a cytology slide removeably attached to an inside surface of a back cover. A sample is removed from the body of a patient, placed in a liquid-based solution, and then on the filter. When the book-like form is closed, the sample is effectively transferred to the slide. The device can be modified so that a plurality of slides are prepared at the same time. Excerpt(s): The present invention relates generally to the preparation of cytology slides and, more particularly, to a device and associated method for preparing cytology slides. Cytology slides are prepared to screen and diagnose cellular samples taken from, for example, samples from the uterine cervix, urine, sputum, blood, fine needle aspiration biopsy, urethral, bronchial brushings and washings, cerebral spinal fluid, and other body fluids. The reliability and efficacy of the screening methods of these slides are measured by their ability to diagnose infections, precancerous lesions or cancerous lesions while at the same time avoiding false positive or negative diagnosis. The reliability of these slides is a primary issue. Often, the results are not accurate or are unreadable. Thus, there is a constant effort to improve the reliability and efficacy in the preparation of cytology samples. One of the most common uses of cytology slides is for screening and diagnosis of a cervical sample. Carcinoma of the cervix is one of the most common malignancies in women, causing nearly 5,000 deaths per year in the United States. Approximately 60% of these cases are associated with absent or deficient screening. Approximately 25% of the screening failures are the result of errors in cervical sampling or smear interpretation.sup.1.sup.1Sawaya, George F. (M.D.), Grimes, David A. (M.D.), "New Technologies in Cervical Cytology Screening: A Word Of Caution", Obstetrics and Gynecology, 1999, Vol. 94, pg.1, which is incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Device for collecting cellular & DNA specimens Inventor(s): Crawford, Paul G.; (Shreveport, LA), Heard, J. S.; (Shreveport, LA), LaBarre, Jacque T.; (Shreveport, LA) Correspondence: John M. Harrison; 2139 E. Bert Kouns; Shreveport; LA; 71105; US Patent Application Number: 20030004435 Date filed: June 21, 2002 Abstract: A device which is suitable for collecting cellular and DNA specimens from the upper vagina and lower cervix of a female patient's reproductive tract. The device can be self-administered by the patient and typically includes an expandible, cell-collecting insert disposed in a compressed configuration in a housing which is initially inserted in the patient's vagina. Upon controlled release from the housing, the insert expands into a generally spherical shape to contact the upper vaginal and lower cervical walls and remains in position for a selected period of time, such as eight hours, during which time some of the vaginal and cervical cells become trapped on the insert. After removal of the insert from the vagina, the insert is placed in a suitable specimen container and the cells thereon are tested for abnormal cytology or various medical conditions such as cancer or sexually transmitted diseases. Excerpt(s): This application claims the benefit of prior filed copending U.S. Provisional Patent Application Serial No. 60/301,313, filed Jun. 28, 2001. This invention relates to

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cell sampling devices and more particularly, to a new and improved device for collecting cellular specimens from biological tissue surfaces and which is suitably adapted for collecting cellular and DNA specimens from the vagina and cervix of the female reproductive tract. The device can be self-administered by a female gynecological patient and includes a cell-collecting insert which in typical use is discharged from a tubular housing into the vagina and expands into a generally spherical or other geometrical configuration for contacting the upper vaginal and lower cervical walls of the patient's reproductive tract. The insert is maintained in position for a selected period of time to collect cells from the vagina and cervix, after which the insert is removed from the vagina, and the cell samples collected thereon are removed and tested for various medical conditions such as cancer or sexually-transmitted diseases or cytological or DNA aberrations. The most common method of retrieving upper vaginal and cervical cell and DNA specimens requires a visit to a physician's office for a speculum-guided pelvic exam. The facility for retrieving such specimens in a home setting, on the other hand, would have multiple uses including, but not limited to, cytologic studies and DNA analysis. Such a technique would afford privacy to patients and result in increased compliance with recommendations for periodic medical evaluation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Filtration system and method for obtaining a cytology layer Inventor(s): Corrigan, Richard W. JR.; (Hawthorn Woods, IL), Mayer, William J.; (South Barrington, IL), Pressman, Norman J.; (Glencoe, IL) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030092170 Date filed: October 21, 2002 Abstract: A filter assembly for separating and collecting a layer of particulate matter (e.g., cells) from a liquid containing the particulate matter (e.g., a biological fluid specimen). The filter assembly has a holder and contiguous inner and outer fluid pervious media. The outer fluid pervious medium is attached to the sidewall of the holder. The inner fluid pervious medium is of low fluidic impedance relative to the outer fluid pervious medium. The filter assembly is designed for use in a separation housing that defines two flow paths between inlet and outlet, one directly through the filter and the other around the periphery of the filter. The inlet portion of the housing has a central inlet in a radially sloped surface that faces the filter collection site. A movable suction head is adapted to cooperate with the housing and the filter assembly. Excerpt(s): This application claims the benefit of commonly owned U.S. provisional application Nos. 60/330,092, filed Oct. 19, 2001, 60/372,080, filed Apr. 15, 2002, and 60/373,658, filed Apr. 19, 2002, all of which are incorporated herein by reference. This application also is related to commonly owned U.S. non-provisional application No. 10/122,151, filed Apr. 15, 2002, which is also incorporated herein by reference. The present disclosure is directed to apparatus and methods for collecting and processing specimens of particulate matter-containing liquid, e.g., biological fluid, including collecting and depositing onto a microscope slide or other surface a uniform layer of particulates therefrom (e.g., cells) suitable for examination (e.g., use in cytology protocols). Diagnostic cytology, particularly in the area of clinical pathology, bases cytological interpretations and diagnoses on examination of cells and other microscopic objects. The accuracy of the screening process and diagnosis, and the preparation of

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optimally interpretable samples from specimens typically depends upon adequate specimen and sample preparation. In this regard the ideal sample would consist of a monolayer of substantially evenly spaced cells, which enables cytotechnologists, cytopathologists, other medical professionals, and automated screening and diagnostic equipment to view or image the cells more clearly so that abnormalities can be identified more readily, more accurately and more reproducibly. Newer methodologies such as immunocytochemistry and cytometric image analysis require preparation apparatus and methods that are safe, effective, accurate, precise, reproducible, inexpensive, efficient, fast and convenient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Highly multiplexed reporter carrier systems Inventor(s): Chait, Brian T.; (New York, NY), Latimer, Darin R.; (East Haven, CT), Lizardi, Paul M.; (Wallingford, CT) Correspondence: Robert A. Hodges, PH.D.; Needle & Rosenberg, P.C.; The Candler Building, Suite 1200; 127 Peachtree Street, N.E.; Atlanta; GA; 30303-1811; US Patent Application Number: 20020106648 Date filed: May 7, 2001 Abstract: Disclosed are a composition and a method for a multiplexing-optimized reporter system. The system is designed for the simultaneous detection of dozens or even hundreds of analytes. The analytes may be present on the surface of cells in suspension, on the surface of cytology smears, on the surface of histological sections, on the surface of DNA microarrays, on the surface of protein microarrays, on the surface of beads, or any other situation where complex samples need to be studied. The disclosed composition accomplishes this detection by associating specific binding molecules-which interact with desired targets--with numerous tag molecules in a carrier. The numerous tag molecules can be detected and effectively amplify the signal generated from targets. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/201,963, filed May 5, 2000, and U.S. Provisional Application 60/224,939, filed Aug. 11, 2000. Application Ser. No. 60/201,963, filed May 5, 2000, and Application No. 60/224,939, filed Aug. 11, 2000, are hereby incorporated herein by reference. The present invention is generally in the field of detection of molecules, and specifically in the field of detection of multiple different molecules in a single assay. It is an object of the present invention to provide a composition that permits the indirect detection of a large number of different analytes in a single sample or group of samples. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of testing adequacy of cells in a specimen Inventor(s): Patterson, Bruce K.; (Chicago, IL) Correspondence: Keith A. Vogt; Niro, Scavone, Haller & Niro; Suite 4600; 181 W. Madison; Chicago; IL; 60602; US Patent Application Number: 20020068315 Date filed: December 10, 2001

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Abstract: The present invention provides a device and method for determining the adequacy of squamous (ectocervical) cells, columnar (endocervical) cells, neutrophils, and noncellular material in a liquid based cytology specimen. The invention first analyzes a liquid based cytology specimen using light scatter to create a light scatter characteristic representing a predetermined cell. Next the invention determines the presence of squamous (ectocervical) cells versus columnar (endocervical) cells versus neutrophils versus noncellular material using the results of the light scatter. The light scatter characteristic that may be used may be forward light scatter, side light scatter, or both side and forward light scatter. Excerpt(s): This application is a continuation-in-part of U.S. Pat. No. 6,329,164, filed Dec. 5, 2000, and granted on Dec. 11, 2001. The present invention relates to an apparatus and method for use in pre-screening or determining the adequacy of target cells in a specimen prior to conducting further diagnostic testing or analysis of the specimen. More specifically, the present invention concerns a device and method which uses light scatter techniques to detect the presence of a target cell in a specimen. Prior to conducting an analysis or testing of a cell specimen, it is important to insure that an adequate amount of target cells are present in the specimen. This is particularly true with respect to pap smear specimens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microscope glass slide for cytology PAP smears Inventor(s): Branch, Vellie; (Fort Washington, MD) Correspondence: Richard C. Litman; Litman Law Offices, LTD.; P.O. Box 15035; Arlington; VA; 22215; US Patent Application Number: 20030021021 Date filed: June 25, 2002 Abstract: A transparent elongated, rectangular glass microscope slide having a specimen observation spot defined by a removable border or frame. The border corresponds to the rectangular perimeter of the glass slide and includes a tab which may be grasped to peel off the border. In use, a cytological GYN PAP smear specimen is placed on the plain glass within the confines of the releasable paper border. The border is then removed after fixing the specimen. The slide also features a frosted end portion for marking identification data. The frosting may include permanent markings such as "NAME" to designate a certain frosted area for marking the desired information such as the patient's name and identification number. A tab is placed on the border end and overlaps a portion of the frosted area, and thus does not protrude outward from the side of the slide. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/307,611, filed Jul. 26, 2001. The present invention relates to microscope slides. More particularly, the invention relates to a slide having a specimen observation spot defined by a removable paper border and a frosted identification portion. Microscope slides are widely used in the health industry. Their use in PAP smear procedures is well known. In conventional slides during analysis or manipulation of the slide the sample or treatment fluid may run off or migrate onto other portions of the slide, "wick off" if the slide touches another object, or suffer cross contamination between slides. It would by desirable to provide a conveniently used slide which avoids these problems.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microvolume liquid dispenser suitable for microarrays and methods related thereto Inventor(s): Korbelik, Jagoda; (Vancouver, CA), MacAulay, Calum E.; (Vancouver, CA) Correspondence: Graybeal Jackson Haley Llp; Suite 350; 155-108th Avenue N.E.; Bellevue; WA; 98004; US Patent Application Number: 20030003025 Date filed: June 19, 2002 Abstract: Microvolume liquid dispensers that provide simple and inexpensive approaches to making cytology microarrays. In some embodiments, the dispensers comprise tips that comprise an outer sleeve, typically shaped like a funnel, that holds a reciprocating needle or pin. The tip of the pin slightly extends beyond the distal opening of the outer sleeve in one position, and is retracted in another position. When the pin is in the distal position the pin contacts the inner surfaces of the sleeve and blocks cytology liquid from flowing through the opening of the sleeve. Thus the pin and sleeve cooperate to form a reservoir behind the blockage. When the pin is pushed up into the sleeve, for example by touching the tip to a glass slide, a passage is formed between the outer surface of the pin and the inner surface of the sleeve. The liquid in the reservoir then flows through the passage and onto the slide. Removing the tip from the substrate moves the pin back to its original position, reforming the reservoir and leaving a predetermined microvolume amount of the liquid on the slide. Excerpt(s): The present application claims priority from U.S. provisional patent application No. 60/298,911, filed Jun. 19, 2001. The field of the present application is micropipettes and microarrays. A "microarray" is a device that is used in biotechnology and other science research. A microarray can be made by putting a large number of tiny samples on a microscope slide (usually made of glass, nylon, plastic, metal, etc.). In a "cytology microarray," the samples are typically individual cells or groups of cells (or disrupted tissue) in a solution such as water and alcohol. In a "tissue microarray," the samples are typically whole tissue (as opposed to the substantially free-floating cells in a cytology microarray). In order to examine the samples in microarray closely, the microarrays are typically stained with special dyes, and/or probed with DNA, proteins or antibodies (or other probes). The microarrays are then examined under a microscope or in a specialized kind of computerized microscope called an image cytometer. This can determine the makeup or identity of the cells or tissues under review. This can be helpful for a variety of medical purposes, such as identifying or diagnosing diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Preservation of RNA and morphology in cells and tissues Inventor(s): Morales, Azorides R.; (Coral Gables, FL), Nadji, Mehrdad; (Miami, FL), Nassiri, Mehdi; (Miami, FL), Vincek, Vladimir; (Aventura, FL) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201; US Patent Application Number: 20030211452 Date filed: May 10, 2002

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Abstract: A solution for preservation and/or storage of a cell or tissue is described. This simple nonaqueous composition can have 10% polyethylene glycol and 90% methanol. It can be used at room temperature. Special chemicals, equipment, and techniques are not needed. Tissue preserved with and/or stored in the solution can be processed for cytology or histology, including chemical staining and/or antibody binding, by a variety of methods; antigen, DNA, and RNA can be extracted from processed tissue in high yield and with minimal or no degradation. Advantages of the solution include: economy and safety, easy access to archival material, and compatibility with both cellular and genetic analyses. The use and manufacture of the solution are also described. Excerpt(s): The present invention relates to a composition containing polyethylene glycol (PEG) and methanol for preservation of a cell or tissue, especially at ambient temperature. It may also be used for cell or tissue storage. A cell or tissue preserved with and/or stored in compositions of the present invention maintains its morphological characteristics, the recognition of its antigens by cognate antibodies, and the integrity of its nucleic acids (e.g., DNA and RNA) without requiring refrigeration or freezing. Cytological and histological processing prevents autolysis of cells and tissue, respectively, after their removal from a living body. Moreover, the structure of individual cells and their organization within the tissue are stabilized by such processing. There is a requirement, however, for sophisticated procedures and dedicated instruments in most cases to process cells and tissues in a clinical setting. Therefore, specimens are usually collected in physician offices or surgical suites, and transported to a centralized pathology service. Suitable compositions for the preservation and/or storage of a cell or tissue are needed to ensure that autolysis is prevented and that cellular morphology, antigen, and nucleic acid are maintained until processing. Furthermore, genetic analysis is becoming more important by itself or complementary to cell staining, enzyme assays, and immunological techniques in pathology. Expression of mutant genes or the over-expression of normal genes can be examined by analyzing nucleic acid. In situ detection of RNA can localize transcripts within tissue containing different types of cells; this can also be accomplished by detecting RNA that has been extracted from different portions of sorted cells or sectioned tissue. Mutations may be seen in DNA or RNA. Alternating cytologic/histologic and genetic analyses of sorted cells or sectioned tissue can be used to correlate pathological events at cellular and molecular levels. Genetic analysis will be possible only if degradation is prevented and macromolecular structures are stabilized. But many preservative compositions and fixatives cause irreversible damage (e.g., activity of the ubiquitous nuclease enzymes, hydrolysis of phosphodiester bonds, and/or deamidation of bases) to the structure of nucleic acids (e.g., DNA, and especially RNA) and reduce their yield, thereby limiting the usefulness of genetic techniques for diagnosis and research applications. Consequently, preservation of nucleic acids in a fresh cell or tissue usually requires special handling, such as immediate processing or freezing, to allow examination by a combination of cytologic, histologic, immunologic, and genetic techniques. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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UNIVERSAL COLLECTION MEDIUM Inventor(s): LORINCZ, ATTILA T.; (NORTH POTOMAC, MD), TANG, YANLIN; (ROCKVILLE, MD) Correspondence: Morgan & Finnegan; 345 Park Avenue; New York; NY; 10154 Patent Application Number: 20030091992 Date filed: December 11, 1998 Abstract: This invention provides a novel universal collection medium for cell collection. The medium allows for the first time the ability to perform cytology and direct molecular analysis on cells preserved in a single sample. This invention also provides novel methods for analyzing cells to assess human conditions. Excerpt(s): The present invention is generally related to the field of cytological and molecular assays and specifically to the area of assays for the assessment of conditions using cytological and molecular assays. The detection and diagnosis of human conditions is of obvious importance for the treatment of disease. Numerous characteristics of diseases have been identified and many are used for their diagnosis. Many diseases are preceded by, and are characterized by, changes in the state of the affected cells. Changes can include the expression of viral genes in infected cells, changes in the expression patterns of genes in affected cells, and changes in cell morphology. The detection, diagnosis, and monitoring of diseases can be aided by the assessment of such cell states. Routinely, for patients suspected of having one or more infectious diseases, for example human papilloma virus or herpes simplex virus, a sample of cells is taken from the patient for analysis. Generally, such a sample is in the form of a swipe or cellular scrape from the area primarily affected by the disease. These swipes usually collect a mixture of normal and diseased cells with a very limited total number of cells. The collected cells are traditionally smeared onto a slide for further analysis. When biochemical analysis was attempted, it was done at the expense of a cytological analysis and was done via qualitative methods such as in situ hybridization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with cytology, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “cytology” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on cytology. You can also use this procedure to view pending patent applications concerning cytology. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON CYTOLOGY Overview This chapter provides bibliographic book references relating to cytology. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on cytology include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “cytology” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on cytology: •

Diagnosis and Treatment Source: in Scully, C. Handbook of Oral Disease: Diagnosis and Management. New York, NY: Thieme New York. 2001. p.385-406. Contact: Available from Thieme New York. 333 Seventh Avenue, New York, NY 10001. (212) 760-0888, ext 110. PRICE: $35.00 plus shipping and handling. ISBN: 1841840874. Summary: This chapter on diagnosis and treatment is the final chapter in a handbook of oral disease that is intended to be used by all members of the dental team who need a ready office reference. The handbook covers the more common and important soft tissue orofacial disorders and gives clinically relevant aspects of the etiology, diagnosis, treatment, and prevention. In this chapter, the authors review certain management procedures that are commonplace. The purpose of making a diagnosis is to be able to offer the most effective treatment, safest treatment, and most accurate prognosis. Diagnosis most importantly involves a careful history. Dental staff should inquire about

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extraoral lesions; observe the patient's affect, behavior, movements, and gait; and inspect and examine the hands, fingers, nails, wrists, face, and neck and cervical lymph nodes. A careful inspection and examination of the oral and perioral structures is mandatory. The authors also discuss diagnostic tests, biopsy, biopsy technique, histology, lymph nodes, the use of frozen sections for rapid diagnosis, and oral smears for cytology. Management issues discussed include oral hygiene, diet, treatment of oral lesions, analgesia (painkillers), immunosuppressive agents, retinoids, antimicrobials, antifungals, antivirals, antidepressants, and when to refer to a specialist. Much of the information is provided in table or outline format for ease of reference. Full color photographs illustrate some conditions. 4 figures. 11 tables. 57 references. •

General Practitioner's Guide to Genitourinary Medicine and Sexual Health Source: Cambridge, England: Cambridge University Press. 1996. 107 p. Contact: Available from Cambridge University Press. 40 West 20th Street, New York, NY 10011-4211. (800) 872-7423. Fax (212) 691-3239. PRICE: $29.95. ISBN: 0521556562. Summary: This illustrated text provides general practitioners with guidelines for diagnosing and managing the many common genitourinary and sexual health problems seen in general practice. The author provides a symptom-oriented approach. Early chapters provide advice on how to take a patient's sexual history and on indications for referral. Seventeen topical chapters cover bacterial vaginosis; candidiasis; other causes of vaginal discharge; a general approach to the management of vaginal discharge; vulval problems; frequency dysuria syndrome; pelvic pain; cytology and colposcopy; contraception and genital tract infection; dysuria in young men; prostatitis, prostatodynia, and hematospermia; scrotal pain; penile rashes; genital ulceration; genital 'lumps'; genital irritation; human immunodeficiency virus (HIV) infection; and genital problems in children. The text is illustrated throughout with black and white photographs; in addition, a section of full-color plates is included. A subject index concludes the volume. 9 references. (AA-M).

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Clinician's Guide to Treatment of Medically Compromised Dental Patients Source: Baltimore, NY: American Academy of Oral Medicine (AAOM). 1995. 82 p. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This monograph, a guide for dentists, is designed to aid in the anticipation, recognition, and management of problems of medically compromised dental patients. The clinician should be able to use this guide to review or become acquainted with the more common medically related disorders that present in the dental office, including: cardiovascular disease; cerebrovascular disease; craniofacial neurology; severe dermatologic disease; endocrine disorders, including diabetes; hematologic disease; hepatitis; neurological disorders; oral cancer; patients with prosthetic devices; pulmonary disease; and renal disease. For each topic, the authors note the definition, etiology, and clinical presentation, notably the oral and dental significance; much of the material is presented in outline or chart form for easy reference. An additional chapter discusses biopsy, cytology, and clinical laboratory procedures.

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Kidney Transplant Rejection: Diagnosis and Treatment. 3rd ed Source: New York, NY: Marcel Dekker, Inc. 1998. 680 p.

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Contact: Available from Marcel Dekker, Inc. Cimarron Road, P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (845) 796-1919. Fax (845) 796-1772. E-mail: [email protected]. International E-mail: [email protected]. Website: www.dekker.com. PRICE: $225.00 plus shipping and handling. ISBN: 0824701399. Summary: This text on kidney transplant rejection is focused on basic immunological principles, mechanisms of rejection, diagnostic modalities, infections in the transplant setting, and clinical treatment of renal allograft rejection. All chapters have been contributed by recognized experts in the field of renal transplantation. Twenty-two chapters cover the molecular basis for transplantation immunity, the mechanisms of cell mediated rejection, cytokines (regulators and effectors of the immune response), regulation of allograft rejection by anti-idiotypic responses, clinical syndromes associated with antibody in allografts, renal injury and preservation in transplantation, mechanism of chronic rejection, xenotransplantation, histocompatibility and organ allocation, immunological tolerance and its relationship to clinical transplantation, pathology of kidney transplantation, fine needle aspiration cytology, the sonographic evaluation of acute renal transplant rejection, the history and prospects for antilymphocyte antibody therapy for tolerance induction, mechanisms of action of immunosuppressive agents (cyclosporine, FK506, rapamycin), the clinical use of cyclosporine in kidney transplantation, tacrolimus and mycophenolate mofetil as primary immunosuppression for renal allograft recipients, newer immunosuppressive agents and combination therapy, immune monitoring for transplant recipients, cancer in recipients of organ allografts, the impact of cytomegalovirus infection on renal transplantation, and hepatitis in the renal allograft recipient. Each chapter, written by experts in the field, includes lengthy references; a subject index concludes the text.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “cytology” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “cytology” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “cytology” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Biopsy Pathology and Cytology of the Cervix (Access to History) by Dulcie V. Coleman, et al; ISBN: 0340740876; http://www.amazon.com/exec/obidos/ASIN/0340740876/icongroupinterna

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Cerebellar dentate nucleus: Organization, cytology and transmitters by Victoria ChanPalay; ISBN: 0387079580; http://www.amazon.com/exec/obidos/ASIN/0387079580/icongroupinterna

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Color Atlas of Cytology of the Dog and Cat by Rebecca Baker, John H. Lumsden; ISBN: 0815104022; http://www.amazon.com/exec/obidos/ASIN/0815104022/icongroupinterna

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Diagnostic Cytology and Hematology of the Dog and Cat by Rick L. Cowell, et al; ISBN: 081510362X; http://www.amazon.com/exec/obidos/ASIN/081510362X/icongroupinterna

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International Review Of Cytology : A Survey of Cell Biology (INTERNATIONAL REVIEW OF CYTOLOGY); ISBN: 0123646375; http://www.amazon.com/exec/obidos/ASIN/0123646375/icongroupinterna

Chapters on Cytology In order to find chapters that specifically relate to cytology, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and cytology using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “cytology” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on cytology: •

Hematuria Source: in Landau, L.; Kogan, B.A. 20 Common Problems in Urology. New York, NY: McGraw-Hill, Inc. 2001. p. 145-166. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070634130. Summary: Hematuria (blood in the urine) is a common problem, and its presence is usually distressing to both patient and health care provider. Hematuria may be the first sign of serious disease in the urinary tract, and is the most common presenting sign of urinary tract cancer and parenchymal (in the tissues of the organ) kidney disease. Blood in the urine is an important symptom that should prompt an appropriate evaluation to rule out or detect disease in otherwise asymptomatic patients. This chapter on hematuria is from a text on common problems in urology (written for the primary care provider). Topics include finding hematuria through dipstick urinalysis, microscopic urinalysis, and erythrocyte (red blood cell) morphology (shape and development); the importance of evaluating hematuria; the differential diagnosis considering renal (kidney) cell carcinoma, transitional cell carcinoma, renal cysts, urolithiasis (urinary tract stones), infection, exercise induced hematuria, benign prostatic hyperplasia (BPH, overgrowth of the prostate), papillary necrosis (tissue death of part of the renal tubules), Berger's disease or immunoglobulin A nephropathy (kidney disease), hematospermia (blood in the semen), and hypercalciuria (excessive calcium in the urine) and hyperuricosuria (excessive uric acid in the urine); key elements to the patient history; and the physical examination and diagnostic tests, including plain film radiography, intravenous pyelogram, ultrasound, computed tomography (CT scan), magnetic resonance imaging (MRI), cystogram, cystoscopy, urine cytology, renal biopsy, and nuclear renal scans. The author also notes special considerations, controversies, and emerging concepts. A patient evaluation algorithm is provided. 14 figures. 13 tables. 20 references.

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Diagnosing Interstitial Cystitis Source: in Moldwin, R.M. Interstitial Cystitis Survival Guide: Your Guide to the Latest Treatment Options and Coping Strategies. Oakland, CA: New Harbinger Publications, Inc. 2000. p. 9-34.

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Contact: Available from Interstitial Cystitis Association. 51 Monroe Street, Suite 1402, Rockville, MD 20850. (800) HELP-ICA or (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $12.00 plus shipping and handling. ISBN: 1572242108. Summary: More than 700,000 Americans have interstitial cystitis (IC), a condition that includes symptoms of recurring bladder pain and discomfort on urination. This chapter on the diagnosis of IC is from a self care book designed to empower readers by simplifying the diagnostic and treatment process for IC. The primary object of the book is to build a framework for delivering proper care to the IC patient. IC is a disease recognized by its symptoms; there are no specific blood or urine tests that firmly tell a clinician whether IC is present or not. The physician reviews the patient's medical history, the physical exam, and other tests designed to make sure that no other disease is present that might cause identical symptoms. The author reviews the list of questions that the doctor may ask at the initial visit, as well as the reasons the questions are asked. These questions include the presence of blood in the urine, a history of bladder infections, the presence of burning on urination, personal or family history of kidney stones, history of sexually transmitted disease, the presence of urinary leakage, the duration of symptoms, the type of pain present and how it changes through the day and night, the role of stress in symptoms, the impact of foods or beverages on the symptoms, sleep disturbance, the use of vaginal douches or other products, painful sexual intercourse, and the urine flow. The chapter then describes what patients can expect during the physical examination and the tests that may be used to diagnosis IC. Tests discussed include urinalysis, urine culture and sensitivity, urine cytology (cell examination), special cultures, the pelvic ultrasound exam, intravenous pyelogram (IVP), urodynamic evaluation (the function of the lower urinary tract during urination), the post void volume assessment (PVR), the cystometrogram (CMG), colposcopy, laparoscopy, cystoscopy, cystoscopy with hydrodistention of the bladder, bladder biopsy, potassium sensitivity test, the response to anesthetic distillation, and urine 'markers' for diagnosis of IC. The chapter concludes with a description of the criteria for IC as established by the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). 5 figures. 2 tables. •

Endoscopic Instrumentation Source: in Cotton, P.B.; Tytgat, G.N.J.; Williams, C.B., eds. Annual of Gastrointestinal Endoscopy. Philadelphia, PA: Current Science. 1991. p. 117-124. Contact: Available from Current Science. 20 North 3rd Street, Philadelphia, PA 191062113. PRICE: $71.25. ISBN: 1870485327. Summary: This article, from a medical compendium of recent research in gastrointestinal (GI) endoscopy, reviews studies published on endoscopic instrumentation. Topics include endoscopes, both fiberoptic and video; computer systems for the endoscopy unit; endoscopic ultrasound, including ultrasound probes, and Doppler probes; and endoscopic accessories, including the variceal ligator, biopsy forceps, gallstone lithotripters, papillotomes, guidewires, stents, cytology brushes, esophageal stents, achalasia dilating balloons, cystoenterostomy device, and bipolar snare. 5 figures. 26 annotated references.

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Chronic Renal Graft Rejection Source: in Paul, L.C. and Solez, K., eds. Organ Transplantation: Long-Term Results. New York, NY: Marcel Dekker, Inc. 1992. p. 153-172.

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Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail: [email protected]. PRICE: $175.00. ISBN: 0824785991. Summary: This book chapter presents a discussion on chronic renal graft rejection, from a British perspective. Topics include a brief history of kidney transplantation; establishing an accurate definition of chronic rejection; diagnostic tests used to confirm chronic rejection, including ultrasound, radionuclide scans, coagulation studies, magnetic resonance imaging, and fine-needle aspiration cytology; the morphology of chronic rejection, including gross appearance, vascular changes, glomerular changes, and the correlation between histological features and clinical outcome; the importance of chronic rejection as a cause of renal allograft failure; and the treatment of chronic rejection. The authors conclude that, if any effective therapeutic intervention is to be made in the processes of chronic rejection, it seems likely that it must be initiated early on in the inflammatory remodeling of the graft vessels. Early markers of chronic rejection are therefore needed, and much interest is presently centered on the growth factors that operate during chronic rejection. 9 figures. 72 references. •

Ureteroscopy Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 941-945. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: This chapter on ureteroscopy (examining and performing surgery on the ureters with a cystoscope) is from an exhaustive textbook on urologic surgery. The ureters have a sinuous course and have three normal anatomic areas of narrowing. The authors note that some particular peculiarities of the ureteral anatomy may render ureteroscopy extremely easy in some patients and difficult, or even impossible, in others. Several factors, even nonpathologic, eventually represent limitations concerning the ureteroscopic examination: position of the ureteral meatus in relation to the bladder neck; the submucosal course; the ureteral hiatus; ureteral diameter and elasticity; its relation to the iliac vessels; and the access angle of the ureteroscope to the upper ureter may be limited by the pubis. The main indications for ureteroscopy are diagnostic, including for ureteral obstruction, filling defects, hematuria (blood in the urine), abnormal urinary cytology, neoplasms, and surveillance; and therapeutic, including for passage of guidewires and catheters, managing stones (fragmentation, removal, displacement), ureterotomy, the biopsy and resection of neoplasms, and retrieval of foreign bodies. The authors detail the surgical techniques used, including instrumentation, ureteroscopes, ureteroscopy, ureteral calculus (stones) manipulation, ureteroscopic calculus fragmentation, postureteroscopy management, hematuria, ureteral tumors, and ureteral strictures. The complication rate ranges from 5 to 14 percent and depends on the equipment, the surgeon's experience, and the size and location of the calculus. Ureteral injury is the most common complication from ureteroscopy. The most common reason that ureteroscopy is utilized and the highest therapeutic success rates are seen in ureteral stones. 4 figures. 2 tables. 8 references.

•

Principles of Differential Diagnosis and Biopsy Source: in Peterson, L.J., et al., eds. Contemporary Oral and Maxillofacial Surgery. 3rd ed. St. Louis, MO: Mosby-Year Book, Inc. 1998. p. 512-532.

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Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. PRICE: $69.00. ISBN: 0815166990. Summary: This chapter, from a textbook that provides a comprehensive description of the basic oral surgery procedures that the general practitioner performs in his or her office, discusses the principles of differential diagnosis and biopsy in oral pathology. The section on examination and diagnostic methods covers health history, history of the lesion, clinical examination, radiographic examination, laboratory investigation, and surgical specimens for pathologic examination. The section on the principles of biopsy covers oral cytology, aspiration biopsy, incisional biopsy, and excisional biopsy. The next section covers soft tissue biopsy techniques and surgical principles, including anesthesia, tissue stabilization, hemostasis, incision, handling of tissue, identification of surgical margins, specimen care, surgical closure, and the biopsy data sheet. Another section discusses intraosseous (hard tissue) biopsy techniques and surgical principles, including aspiration biopsy of radiolucent lesions, mucoperiosteal flaps, osseous window, removal of specimen, and specimen care. The chapter concludes with a section on referrals for biopsy, in which the author discusses factors including the health of the patient, surgical difficulty, and the potential for malignancy. The chapter is illustrated with black and white photographs, drawings, and radiographs. 14 figures. 1 table.

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CHAPTER 6. MULTIMEDIA ON CYTOLOGY Overview In this chapter, we show you how to keep current on multimedia sources of information on cytology. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “cytology” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on cytology: •

Anti - Virals: National Conference on Women and AIDS/HIV Infection; Washington, D.C., December 13 - 14, 1990 Contact: Triad Media Group, PO Box 778, Frederick, MD, 21701, (301) 663-1471. Summary: This sound recording of a presentation from the National Conference on Women and AIDS/HIV Infection held December 13-14, 1990, in Washington, D.C., deals with antiviral drugs to combat or control Human immunodeficiency virus (HIV) infection. The first speaker examines Azidothymidine (AZT). Studies have shown that early antibody testing and treatment may significantly prolong life. Side effects, including changes in vaginal cytology, are discussed. Teratogenic effects and maternal and fetal rights are discussed. The second speaker explains inclusion criteria for Acquired immunodeficiency syndrome (AIDS) clinical trials. Women of childbearing age must agree to abstain from sex or use contraceptives since effects on fetuses are usually unknown. The third speaker analyzes issues in caring for women such as access to insurance, effects of new drugs on female reproductive cycles, and the paperwork and expense of clinical trials for health professionals. The fourth speaker explains the hierarchy of needs for physicians and patients, ethics of clinical trials, and prophylaxis after rape and molestation. The fifth speaker explains that antivirals are often less

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effective in women because they do not enter treatment until late in the course of the disease and may then have less tolerance of side effects. More study is needed on the effects of poverty and homelessness on resistance to HIV.

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CHAPTER 7. PERIODICALS AND NEWS ON CYTOLOGY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover cytology.

News Services and Press Releases One of the simplest ways of tracking press releases on cytology is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “cytology” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to cytology. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “cytology” (or synonyms). The following was recently listed in this archive for cytology: •

HIV-infected women have high abnormal vaginal cytology rates after hysterectomy Source: Reuters Medical News Date: May 11, 2004

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Triennial cervical cancer screening with cytology and HPV DNA testing cost-effective Source: Reuters Medical News Date: April 15, 2004

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UK rolls out liquid-based cytology for cervical cancer Source: Reuters Medical News Date: October 22, 2003

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Routine x-rays, sputum cytology not warranted for lung cancer screening Source: Reuters Medical News Date: September 15, 2003

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UK invites tenders for liquid-based cytology cervical screening Source: Reuters Industry Breifing Date: August 28, 2003

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"Atypical repair" cytology result calls for careful follow-up Source: Reuters Medical News Date: July 01, 2003

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Quick partial scanning of Pap smears can improve quality of cytology programs Source: Reuters Medical News Date: March 12, 2003

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HIV infection predictive of abnormal anal cytology in male adolescents Source: Reuters Medical News Date: February 28, 2003

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Multi-target assay better than cytology in detecting recurrent bladder cancer Source: Reuters Medical News Date: November 05, 2002

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Positive cytology does not contraindicate resection of pancreatic cancer Source: Reuters Medical News Date: June 06, 2002

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Revised guidelines on cervical cytology issued Source: Reuters Medical News Date: April 23, 2002

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Liquid-based cytology backed in Scotland but not in England and Wales Source: Reuters Industry Breifing Date: April 02, 2002

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Abnormal nipple aspiration cytology tied to increased risk of breast cancer Source: Reuters Medical News Date: December 05, 2001

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DNA image cytometry better than urine cytology for bladder cancer screening Source: Reuters Medical News Date: December 11, 2000

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Fine-needle aspiration cytology helpful for diagnosis of small-cell carcinoma Source: Reuters Medical News Date: November 10, 2000

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Anal cytology cost-effective in HIV-negative homosexual, bisexual men Source: Reuters Medical News Date: June 29, 2000

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BTA stat test more sensitive than urine cytology for diagnosis of bladder cancer Source: Reuters Medical News Date: June 05, 2000

Periodicals and News

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Scrape cytology an alternative to frozen-section evaluation of lymph nodes Source: Reuters Medical News Date: January 18, 2000

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HPV testing useful adjunct to cytology for CIN screening in older women Source: Reuters Medical News Date: September 21, 1999

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Investment in new cervical cytology technologies called premature Source: Reuters Medical News Date: August 02, 1999

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ChromaVision gets FDA approval for cytology system Source: Reuters Medical News Date: July 30, 1999

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Suspicious cervical cytology not prognostic in endometrial cancer Source: Reuters Medical News Date: March 12, 1999

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Liquid-based cytology may be more sensitive than conventional Pap smears Source: Reuters Medical News Date: August 10, 1998

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Urine Test More Sensitive Than Cytology For Bladder Cancer Diagnosis Source: Reuters Medical News Date: March 26, 1998

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Rapid Immunoassay Better Than Cytology In Detecting Bladder Cancer Source: Reuters Medical News Date: August 18, 1997

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HCFA Suspends Operation Of Texas Cytology Lab Source: Reuters Medical News Date: June 27, 1996

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Repeat Pap Smear Plus HPV DNA Test Circumvents Need For Colposcopy After Abnormal Cytology Findings Source: Reuters Medical News Date: February 08, 1995

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “cytology” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “cytology” (or synonyms). If you know the name of a company that is relevant to cytology, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “cytology” (or synonyms).

Academic Periodicals covering Cytology Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to cytology. In addition to these sources, you can search for articles covering cytology that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute6: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

6

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.7 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:8 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

7

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 8 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway9 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.10 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “cytology” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 1944280 4000 63 203 94 1948640

HSTAT11 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.12 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.13 Simply search by “cytology” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

9

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

10

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 11 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 12 13

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists14 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.15 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.16 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

14 Adapted 15

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 16 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on cytology can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to cytology. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to cytology. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “cytology”:

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Bladder Cancer http://www.nlm.nih.gov/medlineplus/bladdercancer.html Bladder Diseases http://www.nlm.nih.gov/medlineplus/bladderdiseases.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Kidney Cancer http://www.nlm.nih.gov/medlineplus/kidneycancer.html Lung Cancer http://www.nlm.nih.gov/medlineplus/lungcancer.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on cytology. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Answers to Your Questions About Bladder Cancer Source: Baltimore, MD: American Foundation for Urologic Disease. 1999. 16 p. Contact: Available from American Foundation for Urologic Disease (AFUD). 1128 North Charles Street, Baltimore, MD 21201. (800) 242-2383. Website: www.afud.org. PRICE: $13.00 for pack of 50; plus shipping and handling. Summary: Most bladder cancers can be treated without major surgery. However, early detection is vital; it allows the prompt treatment that gives patients the best chance for a favorable outlook. This brochure, written for people recently diagnosed with bladder cancer, explains how the bladder works, the tests that are used after bladder cancer has been diagnosed (to determine the stage of the cancer), and treatment options. The brochure begins with a six item pretest to determine the reader's knowledge of the bladder and bladder cancer. The lining inside the bladder is composed of a layer of cells that protect the tissues beneath them from urine. A growth, or tumor, means that cells of the bladder lining are producing new cells that are not normal. However, abnormal masses of cells may not always be cancerous. Diagnostic tests to determine the presence and classification of the cancer can include biopsy, intravenous pyelogram, cystoscopy, and urinary cytology. The treatment for bladder cancer depends on how deeply the tumor has grown into the bladder. Removal of a bladder tumor is sometimes called a transurethral resection. In most cases, bladder tumors are superficial and need no

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additional treatment. Often, bladder tumors recur, especially within the first year or two after discovery of the first tumor. In patients with invasive bladder cancer, the surgery may include removal of the entire bladder (cystectomy); chemotherapy may also be indicated. The brochure includes preventive steps to keep the bladder healthy. The brochure concludes with a list of information resources, a glossary of terms used in the text, and the answers to the pretest. 5 figures. 1 table. •

Oral Lesions: Precancerous and Cancerous Growths. Prevention and Early Detection Source: San Bruno, CA: StayWell. 2000. [2 p.]. Contact: Available from StayWell. 1100 Grundy Lane, San Bruno, CA 94066-3030. (800) 333-3032. Fax (650) 244-4512. PRICE: $20.00 for 50 plus shipping and handling. Summary: Precancerous oral lesions are abnormal cell growths in or around the mouth. Cancerous oral lesions are life threatening cell changes in the mouth. This brochure describes precancerous and cancerous oral lesions, emphasizing the importance of early detection of these lesions in order to give that patient a better chance for a cure. The brochure lists the signs and symptoms of precancerous and cancerous lesions; diagnostic approaches, including biopsy, staining, and cytology; treatment options, including surgery, radiation therapy, combination therapy, and chemotherapy; and prevention strategies, including getting oral checkups, not using tobacco, limiting alcohol, eating a healthy diet, and maintaining good oral hygiene. The brochure concludes with a reminder that patients who have precancerous lesions should be followed up closely. The toll free telephone numbers and web sites of the American Cancer Society (www.cancer.org) and the Centers for Disease Control and Prevention (www.cdc.gov) are provided. The brochure is illustrated with simple line drawings. 10 figures.

•

Diagnostic Considerations in Interstitial Dialysis Source: Miami, FL: Baker Norton Pharmaceuticals, Inc. 1992. 7 p. Contact: Available from Baker Norton Pharmaceuticals, Inc. 8800 Northwest 36th Street, Miami, FL 33178-2404. (800) 347-4774. PRICE: Single copy free to health care providers. Summary: The flowchart and notes contained in this booklet outline steps for evaluating a patient with suspected interstitial cystitis (IC). The authors stress that, if the physician learns to recognize typical IC symptoms and has a high degree of suspicion, the diagnosis of IC can be made with reasonable clarity. Topics include the presenting signs and symptoms; patient history; the patient's self-assessment, including the use of a 3 day voiding diary; urine culture; urine cytology; the physical examination; radiography; cystoscopy; inconclusive cystoscopy; biopsy; and urodynamic studies. The booklet includes a detachable, detailed flowchart for physician reference. 2 tables. 5 references.

•

Tissue Sampling and Analysis Source: Manchester, MA: American Society for Gastrointestinal Endoscopy. 1991. 4 p. Contact: Available from American Society for Gastrointestinal Endoscopy. 13 Elm Street, Manchester, MA 01944. (508) 526-8330. PRICE: Single copy free. ASGE Publication No. 1025. Summary: This brochure, one of a series of statements discussing the use of gastrointestinal procedures commonly performed by endoscopists, discusses tissue sampling and analysis. The brochure discusses tissue sampling, including biopsy, snare

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excision, cytology, and culture; techniques and devices; and tissue sampling and analysis in diagnosing problems of the esophagus, stomach, small intestine, and colon. Guidelines for the appropriate use of endoscopy are based on critical review of the available data and expert consensus. 30 references. •

Hematuria: Patient Education Source: Tarrytown, NY: Bayer Corporation. 1999. 11 p. Contact: Available from Bayer Corporation. Diagnostics Division, 511 Benedict Avenue, Tarrytown, NY 10591-5097. (800) 445-5901. PRICE: Single copy free. Summary: This patient education brochure reviews hematuria, the presence of blood in the urine. The brochure defines the condition, describes risk factors and causes, outlines the diagnostic approaches that may be used, reviews treatment options, and offers suggestions for prevention. Hematuria is classified as gross (easily seen) or microscopic (only detected by a microscope or chemical test). Common causes of hematuria are kidney or ureteral stones, cystitis (bladder infection), cancer, enlarged prostate, injury, an underlying medical problem (such as sickle cell anemia and glomerulonephritis, a type of kidney inflammation), medications, and certain foods that can turn the urine red. The brochure notes the risks for different age groups, from newborn through children through three different age groups of adults. Diagnostic strategies include urinalysis, urine culture and sensitivity, urine cytology (cell study), intravenous pyelogram (IVP) or computed tomography (CT scan) urograms, ultrasound, and cystoscopy. Treatment of hematuria depends on the cause of the bleeding and where the bleeding is located. Cystitis is usually treated with antibiotics. Urinary stones are usually broken into smaller pieces by shock waves and then flushed out of the body with the urine. Bladder tumors usually need surgical removal; chemotherapy or radiation therapy may also be indicated. The brochure concludes with a brief glossary of terms and a short list of resources for readers wishing to obtain additional information. A tear-off section lists the topics covered in the booklet; readers are encouraged to check off the items corresponding to issues they would like to discuss with their health care provider and to use the checklist as a reminder tool. 2 figures. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “cytology” (or synonyms). The following was recently posted: •

Cervical cytology practice guidelines Source: American Society of Cytopathology - Professional Association; 2000; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2811&nbr=2037&a mp;string=cytology Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is

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located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Should I Have a Pap Smear? Summary: This educational program was produced and developed by representatives to the Cytopathology Education Consortium to create a public awareness of the importance of gynecologic cytology in the promotion Source: American Society for Clinical Pathology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2307 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to cytology. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to cytology. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with cytology.

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The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about cytology. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “cytology” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “cytology”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “cytology” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “cytology” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.17

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

17

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)18: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

18

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on cytology: •

Basic Guidelines for Cytology Cytology exam of pleural fluid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003866.htm Cytology exam of sputum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003865.htm Cytology exam of urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003905.htm

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Signs & Symptoms for Cytology Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Coughing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm

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Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm •

Diagnostics and Tests for Cytology Bronchoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003857.htm Clean catch urine sample Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm Clean catch urine specimen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm Thoracentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003420.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

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Background Topics for Cytology Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002216.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Epithelial cells Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002358.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Malignancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002253.htm Penis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002279.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm

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Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm Vagina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002342.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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CYTOLOGY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many

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immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the

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preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ameloblastoma: An epithelial tumor of the jaw originating from the epithelial rests of Malassez or from other epithelial remnants of the developing period of the enamel. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration.

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Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphase: The third phase of cell division, in which the chromatids separate and migrate to opposite poles of the spindle. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anaplastic large cell lymphoma: A rare agressive form of lymphoma (cancer that begins in cells of the lymphatic system) that is usually of T-cell origin. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the

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addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anoscopy: A test to look for fissures, fistulae, and hemorrhoids. The doctor uses a special instrument, called an anoscope, to look into the anus. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungals: Drugs that treat infections caused by fungi. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU]

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Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH]

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Ascitic Fluid: The serous fluid which accumulates in the peritoneal cavity in ascites. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory nerve: The eight cranial nerve; also called vestibulocochlear nerve or acoustic nerve. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary lymph nodes: Lymph nodes found in the armpit that drain the lymph channels from the breast. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Backcross: A cross between a hybrid and either one of its parents. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located

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in the basal regions of the cerebral hemispheres. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basilar Artery: The artery formed by the union of the right and left vertebral arteries; it runs from the lower to the upper border of the pons, where it bifurcates into the two posterior cerebral arteries. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Stricture: A narrowing of the biliary tract from scar tissue. The scar tissue may result from injury, disease, pancreatitis, infection, or gallstones. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to

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fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Bladder Neoplasms: Cancer or tumors of the bladder. [NIH] Blastomyces: A genus of onygenacetous mitosporic fungi whose perfect state is Ajellomyces. The species Blastomyces dermatitidis (perfect state Ajellomyces dermatitidis) causes blastomycosis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically

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separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in

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many enzymatic processes. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Cannabis: The hemp plant Cannabis sativa. Products prepared from the dried flowering tops of the plant include marijuana, hashish, bhang, and ganja. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high

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blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to

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cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellular Structures: Components of a cell. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Centrioles: Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical intraepithelial neoplasia: CIN. A general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH]

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Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangiography: Radiographic examination of the bile ducts. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH]

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Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Clavicle: A long bone of the shoulder girdle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colposcopy: The examination, therapy or surgery of the cervix and vagina by means of a specially designed endoscope introduced vaginally. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and

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C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU]

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Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Core biopsy: The removal of a tissue sample with a needle for examination under a microscope. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or

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clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystectomy: Used for excision of the urinary bladder. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU]

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Cystometrogram: A line graph that records urinary bladder pressure at various volumes. [NIH]

Cystoscope: A thin, lighted instrument used to look inside the bladder and remove tissue samples or small tumors. [NIH] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU]

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Dermal: Pertaining to or coming from the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Equipment: Nonexpendable items used in examinination. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digital photography: A type of photography in which images can be viewed on a computer screen. [NIH] Dilate: Relax; expand. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by

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the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dysuria: Painful or difficult urination. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is

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based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as magnetic resonance imaging. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]

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Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocervical curettage: The scraping of the mucous membrane of the cervical canal using a spoon-shaped instrument called a curette. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopic retrograde cholangiopancreatography: ERCP. A procedure to x-ray the pancreatic duct, hepatic duct, common bile duct, duodenal papilla, and gallbladder. In this procedure, a thin, lighted tube (endoscope) is passed through the mouth and down into the first part of the small intestine (duodenum). A smaller tube (catheter) is then inserted through the endoscope into the bile and pancreatic ducts. A dye is injected through the catheter into the ducts, and an x-ray is taken. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH]

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Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [NIH]

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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagectomy: An operation to remove a portion of the esophagus. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]

Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the

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relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroma: A benign tumor of fibrous or fully developed connective tissue. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but

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if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frozen Sections: Thinly cut sections of frozen tissue specimens prepared with a cryostat or freezing microtome. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH]

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Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and

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order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid,

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and amyloid glycoproteins. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulosa Cell Tumor: An ovarian tumor originating in the cells of the primordial membrana granulosa of the graafian follicle. It may be associated with excessive production of estrogen. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynaecological: Pertaining to gynaecology. [EU] Gynecologic cancer: Cancer of the female reproductive tract, including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH]

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Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Haematuria: Blood in the urine. [EU] Hamartoma: A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hazardous Waste: Waste products which, upon release into the atmosphere, water or soil, cause health risks to humans or animals through skin contact, inhalation or ingestion. Hazardous waste sites which contain hazardous waste substances go here. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematoxylin: A dye obtained from the heartwood of logwood (Haematoxylon campechianum Linn., Leguminosae) used as a stain in microscopy and in the manufacture of ink. [NIH] Hematuria: Presence of blood in the urine. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH]

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Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatic Duct, Common: Predominantly extrahepatic bile duct which is formed by the junction of the right and left hepatic ducts, which are predominantly intrahepatic, and, in turn, joins the cystic duct to form the common bile duct. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]

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Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH]

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Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Image Cytometry: A technique encompassing morphometry, densitometry, neural networks, and expert systems that has numerous clinical and research applications and is particularly useful in anatomic pathology for the study of malignant lesions. The most common current application of image cytometry is for DNA analysis, followed by quantitation of immunohistochemical staining. [NIH] Immaturity: The state or quality of being unripe or not fully developed. [EU] Immersion: The placing of a body or a part thereof into a liquid. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort Tlymphocytes into subsets based on CD antigens by the technique of flow cytometry. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by

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inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incisional biopsy: A surgical procedure in which a portion of a lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]

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Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intercellular Junctions: Strictly, and so far as it can be distinguished, the amorphous isotropic layer between adjacent primary walls of cells. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interspecific: Occurring among members of different species. [NIH]

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Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intrathecal chemotherapy: Anticancer drugs that are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. [NIH] Intravenous: IV. Into a vein. [NIH] Intravenous pyelogram: IVP. A series of x-rays of the kidneys, ureters, and bladder. The xrays are taken after a dye is injected into a blood vessel. The dye is concentrated in the urine, which outlines the kidneys, ureters, and bladder on the x-rays. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introgression: The natural spread of genes of one species into another through the process of interspecific hybridization followed by successive backcrosses to the recurrent parents. [NIH]

Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invalidate: To weaken or make valueless : to discredit. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invasive cervical cancer: Cancer that has spread from the surface of the cervix to tissue deeper in the cervix or to other parts of the body. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodine-131: Radioactive isotope of iodine. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one

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direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratoconus: A disorder characterized by an irregular corneal surface (cone-shaped) resulting in blurred and distorted images. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH]

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Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or

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spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]

Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH]

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Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the

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sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Errors: Errors or mistakes committed by health professionals which result in harm to the patient. They include errors in diagnosis (diagnostic errors), errors in the administration of drugs and other medications (medication errors), errors in the performance of surgical procedures, in the use of other types of therapy, in the use of equipment, and in the interpretation of laboratory findings. Medical errors are differentiated from malpractice in that the former are regarded as honest mistakes or accidents while the latter is the result of negligence, reprehensible ignorance, or criminal intent. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]

MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They

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include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methacrylate: A vinyl monomer. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH]

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Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Micromanipulators: A high precision instrument used in microinjection or chromosome dissection activities. [NIH] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to molecules with the desired properties. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two

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hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH]

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Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroectodermal tumor: A tumor of the central or peripheral nervous system. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between

Dictionary 235

experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nipple discharge: Fluid coming from the nipple. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the

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next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncogenic Viruses: Viruses that produce tumors. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of

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oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orderly: A male hospital attendant. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocytes: Mature osteoblasts that have become embedded in the bone matrix. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH]

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Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pap test: The collection of cells from the cervix for examination under a microscope. It is used to detect changes that may be cancer or may lead to cancer, and can show noncancerous conditions, such as infection or inflammation. Also called a Pap smear. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Papovaviridae: A family of small, non-enveloped DNA viruses affecting mostly mammals. Most members can induce tumors in hosts. There are two genera: Papillomavirus and Polyomavirus. [NIH] Paracoccidioidomycosis: A mycosis affecting the skin, mucous membranes, lymph nodes, and internal organs. It is caused by Paracoccidioides brasiliensis. It is also called paracoccidioidal granuloma. Superficial resemblance of P. brasiliensis to Blastomyces brasiliensis (blastomyces) may cause misdiagnosis. [NIH] Paracrine Communication: Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of hormones on surrounding cells. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Parthenogenesis: A specialized type of apomixis in which an organism develops from an unfertilized female gamete. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (=

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branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Perioral: Situated or occurring around the mouth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Lavage: Washing out of the peritoneal cavity. The procedure is a diagnostic as well as a therapeutic technique following abdominal trauma or inflammation. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal

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layer of the bowel wall. [NIH] Pesticide Residues: Pesticides or their breakdown products remaining in the environment following their normal use or accidental contamination. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pipette: Tube designed to measure liquids in drops. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of

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organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their

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complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyomavirus: A genus of the family papovaviridae consisting of potentially oncogenic viruses normally present in the host as a latent infection. The virus is oncogenic in hosts different from the species of origin. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU]

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Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Primary tumor: The original tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic

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epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and

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treatment of mental disorders. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH]

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Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiolucent: Partly or wholly permeable to X-rays or other forms of radiation contrasted with radiopaque. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference point: The midpoint of a line connecting the centers of the two end faces of the acoustic test fixture. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is

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incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cysts: Abnormal fluid-filled sacs in the kidney that range in size from microscopic to much larger. Many simple cysts are harmless, while other types can seriously damage the kidneys. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Reproductive History: An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The

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outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatoid Nodule: Subcutaneous nodules seen in 20-30% of rheumatoid arthritis patients. They may arise anywhere on the body, but are most frequently found over the bony prominences. The nodules are characterized histologically by dense areas of fibrinoid necrosis with basophilic streaks and granules, surrounded by a palisade of cells, mainly fibroblasts and histiocytes. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room

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temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU]

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Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous Epithelium: Specialized epithelium lining the seminiferous tubules containing developing and mature spermatozoa and Sertoli cells. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sentinel lymph node: The first lymph node that cancer is likely to spread to from the primary tumor. Cancer cells may appear first in the sentinel node before spreading to other lymph nodes. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Ratio: The number of males per 100 females. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round

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when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Iodide: Sodium iodide (NaI). A compound forming white, odorless deliquescent crystals and used as iodine supplement, expectorant or in its radioactive (I-131) form as an diagnostic aid, particularly for thyroid function determinants. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Space Flight: Travel beyond the earth's atmosphere. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU]

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Speculum: An instrument used to widen an opening of the body to make it easier to look inside. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Squamous intraepithelial lesion: SIL. A general term for the abnormal growth of squamous cells on the surface of the cervix. The changes in the cells are described as low grade or high grade, depending on how much of the cervix is affected and how abnormal the cells appear. [NIH]

Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Standardize: To compare with or conform to a standard; to establish standards. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent

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carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH]

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Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraclavicular: The depression above the clavicle and lateral to the sternomastoid muscle. [NIH]

Supraclavicular lymph nodes: Lymph nodes located above the clavicle (collar bone). [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Syringoma: Adenoma of the sweat glands. [NIH] Systemic: Affecting the entire body. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Technology Transfer: Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise. [NIH]

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Telecommunications: Transmission of information over distances via electronic means. [NIH]

Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH]

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Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroid Neoplasms: Tumors or cancer of the thyroid gland. [NIH] Thyroid Nodule: A small circumscribed mass of differentiated tissue associated with the thyroid gland. It can be pathogenic or non-pathogenic. The growth of nodules can lead to a condition of nodular goiter. Most nodules appear between the ages of 30 and 50 years and most are benign. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Fixation: The technique of using fixatives in the preparation of cytologic, histologic, or pathologic specimens for the purpose of maintaining the existing form and structure of all the constituent elements. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH]

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Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Transitional cells: Cells that vary in shape depending on whether the tissue is being stretched. The cells may be stretched without breaking apart. They line hollow organs such as the bladder. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA

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(ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Ureteroscope: A tool for examining the bladder and ureters and for removing kidney stones through the urethra. The procedure is called ureteroscopy (yoo-ree-tur-AH-skoh-pee). [NIH] Ureteroscopy: Endoscopic examination, therapy or surgery of the ureter. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urolithiasis: Stones in the urinary system. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases

Dictionary 259

of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urothelium: The epithelial lining of the urinary tract. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginal Discharge: A common gynecologic disorder characterized by an abnormal, nonbloody discharge from the genital tract. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]

260

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Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be

Dictionary 261

placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zygomycosis: Infection in humans and animals caused by fungi in the class Zygomycetes. It includes mucormycosis and entomophthoramycosis. The latter is a tropical infection of subcutaneous tissue or paranasal sinuses caused by fungi in the order Entomophthorales. Phycomycosis, closely related to zygomycosis, describes infection with members of Phycomycetes, an obsolete classification. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

263

INDEX 3 3-dimensional, 57, 189 A Abdomen, 189, 198, 212, 225, 227, 228, 230, 231, 236, 237, 239, 248, 252, 253, 260 Abdominal, 189, 208, 225, 237, 238, 239, 248, 258 Aberrant, 126, 189 Ablation, 13, 189 Abrasion, 44, 189 Absolute risk, 50, 189 Acetone, 115, 189, 226 Acetylcholine, 7, 189, 191, 235 Acetyltransferases, 54, 189 Acidity, 189, 240 Acne, 189, 248 Acoustic, 189, 195, 246 Acrylonitrile, 189, 249 Actin, 189, 234 Acute leukemia, 77, 189 Acute myelogenous leukemia, 189, 190 Acute myeloid leukemia, 54, 189, 190 Acute nonlymphocytic leukemia, 189 Acute renal, 153, 190 Adaptability, 190, 200, 201 Adaptation, 190, 241 Adenocarcinoma, 3, 23, 48, 61, 71, 91, 92, 98, 122, 190, 220, 235, 244 Adenovirus, 16, 190 Adenylate Cyclase, 190, 202 Adjustment, 130, 190 Adjuvant, 137, 190 Adjuvant Therapy, 137, 190 Adsorption, 44, 190 Adsorptive, 190 Adverse Effect, 190, 250 Affinity, 25, 190, 251 Affinity Chromatography, 25, 190 Agar, 190, 241 Age Groups, 176, 191 Aged, 80 and Over, 191 Agonists, 26, 191 Agrin, 7, 191 Airway, 9, 53, 94, 191 Albumin, 191, 254 Algorithms, 57, 134, 191, 197 Alkaline, 191, 198 Alleles, 191, 228

Allergen, 9, 191, 208 Allogeneic, 191, 218 Allograft, 153, 156, 191 Alpha Particles, 191, 245 Alternative medicine, 164, 191 Alveolar Process, 191, 247 Ameloblastoma, 77, 191 Amino acid, 191, 192, 193, 194, 206, 216, 217, 239, 244, 248, 254, 256, 257, 258 Amino Acid Sequence, 192, 193, 216 Amplification, 192, 232 Ampulla, 192, 211 Amyloid, 73, 192, 218 Anaerobic, 192, 259 Anaesthesia, 192, 223 Anal, 10, 44, 61, 69, 84, 94, 162, 192, 215, 233 Analog, 192, 215 Analogous, 10, 192, 257 Analytes, 123, 145, 192 Anaphase, 24, 192 Anaphylatoxins, 192, 204 Anaplasia, 192, 244 Anaplastic, 75, 192 Anaplastic large cell lymphoma, 75, 192 Anatomical, 32, 89, 192, 210, 238 Anemia, 176, 192, 196, 255 Anesthesia, 157, 191, 192 Aneuploidy, 25, 40, 48, 90, 192 Angiogenesis, 193, 230 Animal model, 10, 25, 53, 56, 193 Anions, 191, 193, 226 Annealing, 193, 241 Anoscopy, 10, 45, 193 Antibacterial, 193, 251 Antibiotic, 193, 198, 251 Antibodies, 9, 25, 33, 35, 115, 121, 123, 141, 142, 147, 148, 193, 212, 219, 222, 229, 233, 241 Antibody therapy, 153, 193 Anticoagulant, 193, 244 Antifungals, 152, 193 Antigen, 27, 37, 115, 121, 142, 148, 190, 193, 204, 207, 221, 222, 223, 250 Antigen-Antibody Complex, 193, 204 Antigen-presenting cell, 193, 207 Anti-infective, 193, 225 Anti-inflammatory, 194, 238

264

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Antimetabolite, 194, 215 Antineoplastic, 194, 215 Antioxidant, 194, 237 Antiseptic, 189, 194 Antiviral, 5, 159, 194, 224 Anus, 80, 192, 193, 194, 198, 203, 246 Apoptosis, 6, 34, 52, 54, 90, 194 Applicability, 7, 61, 133, 136, 194 Aqueous, 194, 207, 210, 227 Archaea, 194, 231 Arginine, 49, 192, 194, 220, 235 Arterial, 194, 221, 244 Arteries, 194, 196, 197, 205, 231, 245 Arterioles, 194, 197, 199 Artery, 194, 196, 197, 206, 238, 245, 259 Artifacts, 112, 194 Asbestos, 194, 230, 231 Ascites, 119, 194, 195 Ascitic Fluid, 94, 195 Aseptic, 195, 253 Assay, 5, 6, 8, 27, 32, 51, 77, 88, 117, 123, 141, 145, 162, 195 Asymptomatic, 28, 42, 63, 117, 154, 195, 196, 238 Ataxia, 195, 221 Attenuated, 195, 259 Atypical, 41, 64, 66, 67, 79, 87, 88, 162, 195 Auditory, 195, 230 Auditory nerve, 195, 230 Autologous, 18, 195 Autolysis, 148, 195 Autonomic, 189, 195, 239 Autoradiography, 20, 36, 195 Axillary, 69, 82, 99, 195 Axillary lymph nodes, 69, 99, 195 Axons, 7, 195, 207, 224, 236, 243, 245 B Backcross, 42, 195 Bacteriophage, 195, 241, 257 Bacteriuria, 195, 258 Basal cells, 12, 195 Basal Ganglia, 107, 195, 198, 245 Basement Membrane, 16, 196, 199, 213, 227 Basilar Artery, 196, 230 Basophils, 16, 196, 227 Benign, 4, 61, 72, 131, 154, 196, 198, 214, 219, 231, 234, 238, 246, 256, 260 Benign prostatic hyperplasia, 154, 196 Benign tumor, 196, 214 Beta-pleated, 192, 196 Beta-Thalassemia, 60, 196

Bile, 11, 116, 196, 202, 211, 216, 220, 221, 228, 243, 253 Bile Acids, 196, 253 Bile Acids and Salts, 196 Bile duct, 11, 116, 196, 202, 211, 220, 243 Biliary, 59, 63, 83, 87, 95, 111, 133, 196, 238 Biliary Stricture, 87, 196 Biliary Tract, 59, 63, 133, 196, 238 Bioavailability, 196, 223 Biochemical, 11, 14, 19, 25, 39, 52, 53, 56, 67, 78, 121, 142, 149, 191, 194, 196, 197, 215, 217, 227 Bioengineering, 7, 25, 168, 196 Biological therapy, 196, 218 Biological Transport, 197, 208 Biomarkers, 12, 13, 21, 197 Biopolymers, 47, 197 Biopsy specimen, 24, 56, 135, 136, 197 Biosynthesis, 197, 244 Biotechnology, 49, 58, 147, 164, 169, 197 Biotransformation, 14, 197 Bladder Neoplasms, 88, 197 Blastomyces, 197, 238 Blood Coagulation, 197, 198, 255 Blood Glucose, 197, 219, 224 Blood pressure, 197, 200, 221, 233, 245, 251 Blot, 77, 197 Blotting, Western, 54, 197 Body Fluids, 119, 121, 130, 142, 143, 197, 198, 209, 251, 257 Bone Marrow, 49, 67, 189, 190, 198, 206, 216, 218, 229, 253 Bone Resorption, 25, 198 Bone scan, 198, 249 Bowel, 192, 198, 208, 225, 239, 253, 258 Bowel Movement, 198, 208, 253 Brachytherapy, 198, 224, 226, 245, 261 Bradykinin, 198, 235 Brain Neoplasms, 198, 221 Breast Feeding, 198, 247 Breeding, 42, 198 Broad-spectrum, 11, 49, 198 Bronchi, 198, 213, 256 Bronchial, 22, 63, 70, 143, 198 Bronchoalveolar Lavage, 64, 198 Bronchus, 121, 141, 198 C Calcium, 38, 154, 194, 198, 203, 221, 230, 232 Calibration, 130, 199 Candidiasis, 117, 152, 199 Candidosis, 199

265

Cannabidiol, 199 Cannabinoids, 26, 199 Cannabinol, 199 Cannabis, 90, 199, 255 Cannula, 112, 199 Capillary, 16, 36, 38, 198, 199, 259 Carbohydrate, 11, 199, 217, 242 Carbon Dioxide, 199, 215, 247 Carcinogen, 11, 199 Carcinogenesis, 11, 14, 37, 51, 199, 202 Carcinogenic, 199, 224, 236, 243, 253 Carcinoma in Situ, 21, 22, 141, 199 Cardiac, 8, 49, 199, 210, 211, 213, 233, 253 Cardiovascular, 43, 84, 101, 135, 152, 199 Cardiovascular disease, 43, 152, 199 Carotene, 24, 200, 248 Carotenoids, 24, 200 Case report, 67, 75, 78, 85, 90, 91, 92, 200 Catheter, 111, 112, 115, 116, 133, 200, 211, 225, 228 Catheterization, 133, 200, 225 Cations, 200, 226 Caudate Nucleus, 200, 206, 234 Cell Adhesion, 9, 200 Cell Adhesion Molecules, 9, 200 Cell Communication, 12, 200 Cell Cycle, 24, 29, 39, 54, 200, 227, 244 Cell Death, 54, 194, 200, 201, 234 Cell Differentiation, 7, 49, 200 Cell Division, 24, 40, 192, 195, 200, 201, 207, 218, 230, 231, 232, 240, 243, 250, 255 Cell Lineage, 12, 200 Cell membrane, 7, 27, 197, 200, 207, 216, 225 Cell motility, 57, 200 Cell Physiology, 57, 200 Cell proliferation, 12, 29, 62, 201, 224, 236 Cell Size, 201, 215 Cell Survival, 201, 218 Cellular Structures, 30, 55, 131, 201 Cellulose, 201, 216, 240 Central Nervous System, 189, 198, 201, 216, 217, 219, 221, 236 Central Nervous System Infections, 201, 219, 221 Centrifugation, 119, 131, 201 Centrioles, 201, 243 Cerebellar, 97, 153, 195, 201 Cerebellum, 198, 201, 206 Cerebral, 35, 143, 195, 196, 198, 201, 206, 213, 214, 221, 245, 255 Cerebrospinal, 48, 83, 119, 201, 221

Cerebrospinal fluid, 48, 83, 119, 201, 221 Cerebrovascular, 152, 199, 201 Cerebrum, 201, 206, 255, 257 Cervical intraepithelial neoplasia, 22, 67, 68, 201 Chemokines, 9, 202 Chemoprevention, 22, 202 Chemopreventive, 22, 202 Chemotactic Factors, 202, 204 Chemotaxis, 44, 202 Chemotherapy, 5, 52, 89, 99, 137, 175, 176, 190, 202 Chlamydia, 50, 117, 202 Chlorophyll, 202, 216 Cholangiography, 112, 202 Cholera, 39, 202, 260 Cholera Toxin, 39, 202 Cholesterol, 37, 196, 202, 206, 253 Chondrocytes, 202, 214 Choroid, 48, 202, 247 Chromatin, 54, 194, 202, 212, 235, 252, 255 Chromium, 89, 202 Chromosomal, 24, 40, 54, 192, 202, 217, 220, 232 Chromosome, 6, 15, 24, 40, 193, 202, 219, 228, 232, 233, 250, 257 Chromosome Segregation, 24, 40, 202 Chronic, 5, 13, 44, 49, 153, 155, 156, 203, 212, 213, 223, 226, 227, 238, 244, 253, 258 Chronic Disease, 44, 203, 227 Chronic renal, 156, 203 Clavicle, 203, 254 Clinical Medicine, 203, 242 Clinical trial, 5, 20, 27, 35, 37, 159, 169, 203, 205, 206, 239, 244, 246 Clone, 25, 203 Cloning, 15, 124, 125, 197, 203, 224 Coenzyme, 189, 203 Cofactor, 10, 203, 244, 255 Collagen, 192, 196, 203, 214, 230, 241 Colon, 21, 116, 121, 141, 176, 203, 227, 258 Colorectal, 52, 63, 100, 203 Colorectal Cancer, 52, 100, 203 Colposcopy, 36, 46, 60, 69, 72, 91, 98, 122, 152, 155, 163, 203 Combination chemotherapy, 52, 203 Complement, 11, 192, 203, 204, 217, 229 Complementary and alternative medicine, 105, 106, 204 Complementary medicine, 105, 204 Compliance, 144, 204 Computational Biology, 169, 204

266

Cytology

Computed tomography, 154, 176, 204, 249 Computer Systems, 155, 204 Computerized axial tomography, 204, 249 Computerized tomography, 204 Conception, 204, 205, 214, 253 Cone, 134, 205, 226 Conjunctiva, 205 Conjunctivitis, 70, 205 Connective Tissue, 198, 203, 205, 214, 216, 229, 231, 248, 249, 255 Connexins, 36, 205, 216 Consolidation, 18, 205 Constriction, 205, 226 Consultation, 16, 19, 20, 205, 213 Contamination, 111, 114, 120, 123, 124, 146, 205, 240 Contraception, 45, 152, 205 Contraceptive, 205, 247 Contractility, 53, 205 Contraindications, ii, 205 Contrast Media, 112, 205 Contrast medium, 133, 205 Controlled study, 36, 205 Coordination, 57, 201, 205 Core biopsy, 59, 99, 205 Cornea, 36, 60, 80, 87, 205, 218, 253 Coronary, 199, 205, 206, 231 Coronary heart disease, 199, 205 Coronary Thrombosis, 206, 231 Corpus, 206, 234, 243, 260 Corpus Striatum, 206, 234 Cortices, 35, 206 Cotinine, 41, 206 Cowpox, 206, 259 Cowpox Virus, 206, 259 Craniocerebral Trauma, 206, 219, 221 Crossing-over, 206, 246 Cryostat, 20, 206, 215 Cues, 54, 206 Cultured cells, 16, 51, 53, 206 Curative, 92, 206, 255 Curettage, 132, 206 Curette, 120, 122, 206, 211 Cutaneous, 199, 206, 259 Cyclic, 19, 38, 190, 200, 206, 218, 235 Cyclosporine, 153, 206 Cyst, 81, 206 Cystectomy, 175, 206 Cysteine, 202, 206, 211 Cystitis, 154, 155, 175, 176, 206 Cystometrogram, 155, 207 Cystoscope, 156, 207

Cystoscopy, 154, 155, 174, 175, 176, 207 Cytogenetics, 103, 135, 207 Cytokine, 9, 18, 45, 207 Cytomegalovirus, 153, 207 Cytoplasm, 126, 129, 194, 196, 200, 202, 207, 212, 235, 248, 255 Cytosine, 53, 207 Cytoskeleton, 12, 19, 38, 207, 232 Cytotoxic, 37, 45, 207, 222, 246 D Decision Making, 54, 207 Degenerative, 207, 220 Dehydration, 202, 207 Deletion, 194, 207, 228 Denaturation, 207, 241 Dendrites, 207, 234, 245 Dendritic, 18, 33, 207, 230 Dendritic cell, 18, 33, 207 Density, 19, 36, 112, 118, 129, 134, 201, 207, 215, 236, 241 Dentate Gyrus, 26, 207, 220 Dentists, 152, 207 Depolarization, 26, 207 Dermal, 36, 67, 208 Desensitization, 208, 222 Developing Countries, 73, 208, 254 Developmental Biology, 30, 208 Diabetes Mellitus, 47, 208, 217, 219 Diagnostic Equipment, 145, 208 Diagnostic Errors, 32, 208, 230 Diagnostic procedure, 109, 121, 142, 164, 208 Diaphragm, 208, 241 Diffusion, 35, 197, 208, 223, 225 Digestion, 196, 198, 208, 225, 228, 253, 259 Digestive system, 6, 208 Digestive tract, 208, 251, 252 Digital photography, 16, 208 Dilate, 111, 208 Dilation, 83, 198, 208, 221 Diploid, 40, 193, 208, 233, 241, 257 Direct, iii, 14, 27, 43, 48, 50, 96, 98, 111, 112, 114, 115, 131, 149, 200, 203, 208, 246, 254 Discrete, 91, 135, 136, 208, 255 Dispenser, 147, 208 Disposition, 14, 139, 208 Dissection, 6, 208, 232 Dissociation, 122, 142, 190, 208 Distal, 11, 111, 112, 113, 116, 122, 133, 136, 138, 147, 209, 210, 243 Dominance, 209, 212

267

Dosimetry, 35, 36, 209 Drive, ii, vi, 6, 15, 20, 29, 53, 124, 152, 157, 209, 226 Drug Combinations, 5, 209 Drug Interactions, 209 Drug Resistance, 5, 209 Drug Tolerance, 209, 256 Duct, 111, 115, 116, 133, 192, 199, 200, 209, 211, 213, 220, 229, 249, 253, 254 Duodenum, 133, 196, 209, 211, 237, 238, 253 Dyes, 147, 192, 196, 209, 215, 235 Dynein, 25, 209 Dysplasia, 4, 10, 21, 23, 48, 132, 209 Dysuria, 152, 209 E Edema, 38, 209, 225, 226 Effector, 38, 189, 203, 209 Efficacy, 21, 35, 36, 39, 53, 64, 70, 98, 143, 209, 228 Effusion, 69, 70, 71, 73, 210 Ejaculation, 210, 250 Elasticity, 156, 210 Electrode, 8, 125, 210 Electrolyte, 210, 242, 251 Electromyography, 28, 210 Electron microscope, 16, 36, 53, 210 Electron Spin Resonance Spectroscopy, 14, 210 Electrons, 194, 210, 226, 237, 245, 246 Electrophysiological, 26, 210 Embryo, 40, 200, 210, 223, 231, 252 Embryology, 55, 210 Emulsion, 195, 210, 215 Enamel, 191, 210 Encapsulated, 47, 210 Endemic, 13, 22, 202, 210 Endocarditis, 199, 211 Endocervical curettage, 71, 122, 132, 211 Endocrine System, 211, 234 Endocrinology, 211, 218 Endogenous, 26, 37, 211, 244, 257 Endometrial, 71, 163, 211 Endometrium, 211, 218 Endopeptidases, 211, 244 Endoscope, 111, 116, 133, 136, 138, 203, 211 Endoscopic, 3, 28, 48, 71, 76, 111, 112, 133, 136, 155, 207, 211, 258 Endoscopic retrograde cholangiopancreatography, 112, 211 Endoscopy, 83, 101, 155, 175, 176, 211

Endothelial cell, 16, 33, 36, 38, 44, 211, 214, 255 Endothelium, 12, 53, 211, 235 Endothelium, Lymphatic, 211 Endothelium, Vascular, 211 Endothelium-derived, 211, 235 Endotoxic, 212, 228 Endotoxins, 204, 212 End-stage renal, 47, 203, 212 Entorhinal Cortex, 212, 220 Environmental Health, 14, 43, 168, 170, 212 Enzymatic, 53, 192, 199, 200, 204, 212, 242, 248 Enzyme, 8, 39, 148, 190, 203, 209, 212, 216, 218, 229, 241, 244, 254, 255, 256, 260, 261 Eosinophils, 212, 227 Epidemic, 44, 212 Epidemiological, 13, 212, 247 Epidermis, 195, 212 Epidermoid carcinoma, 212, 252 Epigastric, 212, 237 Epistasis, 29, 212 Epithelial Cells, 9, 21, 23, 38, 48, 126, 202, 212, 227 Epithelium, 27, 49, 80, 89, 196, 211, 212, 226, 238, 244, 250 Epitope, 18, 115, 212 Epitope Mapping, 18, 212 Equipment and Supplies, 43, 212 Erythrocytes, 192, 198, 213 Escalation, 27, 213 Esophageal, 3, 27, 96, 138, 155, 213 Esophagectomy, 4, 213 Esophagitis, 27, 213 Esophagus, 3, 12, 48, 66, 116, 138, 176, 208, 213, 219, 246, 252, 253 Estrogen, 23, 213, 218 Eukaryotic Cells, 213, 223, 236, 237, 258 Evoke, 213, 253 Excisional, 32, 55, 122, 157, 213 Excisional biopsy, 55, 157, 213 Excitability, 26, 213 Excitation, 56, 213, 215, 235 Excitatory, 213, 217 Exocrine, 213, 237 Exogenous, 26, 190, 197, 211, 213, 244 Expectorant, 213, 251 Expert Systems, 213, 222 External-beam radiation, 213, 226, 245, 260

268

Cytology

Extracellular, 12, 25, 48, 55, 192, 205, 213, 214, 230, 237, 251 Extracellular Matrix, 12, 55, 205, 213, 214, 230, 237 Extracellular Matrix Proteins, 213, 230 Extracellular Space, 213, 214 Extraction, 46, 123, 133, 214 Extremity, 47, 113, 214 Eye Infections, 190, 214 Eye Movements, 29, 214 F Facial, 214, 230, 238 Facial Nerve, 214, 238 Fallopian tube, 214, 218, 247 Family Planning, 86, 169, 214 Fat, 196, 198, 200, 206, 214, 226, 228, 248, 251, 254 Fatigue, 33, 126, 214 Fetus, 214, 242, 252, 259 Fibroblast Growth Factor, 49, 81, 214 Fibroblasts, 9, 214, 248 Fibroma, 61, 214 Fibrosis, 16, 214 Fissure, 207, 214 Fixation, 19, 81, 128, 214 Fixatives, 115, 148, 215, 256 Flow Cytometry, 14, 18, 55, 87, 90, 94, 215, 222 Fluorescence, 14, 17, 25, 30, 33, 36, 47, 56, 88, 122, 142, 215 Fluorescent Dyes, 215 Fluoroscopy, 116, 215 Fluorouracil, 52, 215 Fold, 21, 214, 215, 236 Foramen, 215, 230, 239 Fovea, 215 Fractionation, 19, 215 Frozen Sections, 115, 152, 215 Fungi, 193, 197, 214, 215, 216, 231, 232, 252, 255, 259, 261 Fungus, 60, 199, 216, 233 G Gait, 152, 216 Gallbladder, 189, 196, 208, 211, 216, 228 Gamma Rays, 216, 245, 246 Ganglia, 189, 216, 234, 239 Gap Junctions, 205, 216 Gas, 199, 208, 216, 221, 235, 254 Gastric, 63, 72, 76, 78, 92, 94, 216, 219 Gastrin, 216, 221 Gastrointestinal, 6, 76, 83, 95, 133, 135, 155, 175, 194, 198, 216, 253, 254, 258, 260

Gastrointestinal tract, 6, 76, 95, 135, 216, 253, 258 Gene Expression, 5, 22, 25, 30, 47, 51, 54, 57, 216 Gene Expression Profiling, 30, 216 Gene Therapy, 16, 190, 216 General practitioner, 152, 157, 216 Genetic Code, 216, 235 Genetic Engineering, 197, 203, 217 Genetic Techniques, 148, 217 Genetic testing, 217, 242 Genetics, 14, 24, 28, 40, 42, 56, 57, 207, 209, 217 Genital, 36, 50, 122, 140, 152, 217, 218, 258, 259 Genomics, 6, 16, 24, 46, 217 Genotype, 217, 240 Germ Cells, 217, 230, 237, 251, 252 Gestation, 217, 252 Gland, 23, 61, 67, 91, 95, 96, 98, 101, 217, 229, 230, 237, 238, 240, 243, 249, 253, 254, 255, 256 Glomerular, 100, 156, 217 Glomeruli, 217 Glomerulonephritis, 176, 217 Glomerulus, 217 Glucose, 11, 47, 197, 201, 202, 208, 217, 219, 224, 249 Glucose Intolerance, 208, 217 Glutamate, 217 Glutamic Acid, 47, 217, 235 Glycogen, 11, 202, 217 Glycolysis, 11, 217 Glycoproteins, 200, 217, 244 Glycosaminoglycan, 39, 218 Goiter, 218, 256 Gonadal, 218, 253 Gonorrhea, 117, 218 Governing Board, 218, 242 Grade, 4, 39, 41, 44, 45, 48, 64, 86, 87, 95, 218, 244, 252 Grading, 20, 48, 77, 218 Graft, 155, 156, 218, 233 Graft Rejection, 155, 156, 218 Graft-versus-host disease, 218, 233 Gram-negative, 202, 212, 218, 260 Granule, 207, 218, 248 Granuloma, 218, 238 Granulosa Cell Tumor, 62, 84, 218 Growth factors, 9, 42, 49, 156, 218, 236 Guanylate Cyclase, 218, 235 Gynaecological, 73, 218

269

Gynecologic cancer, 123, 218 Gynecology, 24, 31, 59, 65, 66, 67, 76, 86, 136, 140, 143, 218 H Haematological, 121, 141, 219 Haematology, 219 Haematuria, 97, 219 Hamartoma, 74, 219 Haploid, 40, 219, 241 Haplotypes, 16, 42, 219 Haptens, 190, 219 Hazardous Waste, 111, 219 Headache, 219, 221 Heart attack, 199, 219 Heartburn, 28, 219 Hematology, 35, 135, 153, 219 Hematopoiesis, 54, 219 Hematopoietic Stem Cells, 49, 54, 219 Hematoxylin, 48, 137, 219 Hematuria, 154, 156, 176, 219 Hemoglobin, 19, 192, 196, 213, 219, 255 Hemoglobin A, 19, 219 Hemoglobinopathies, 216, 219 Hemorrhoids, 193, 220 Hemostasis, 157, 220 Hepatic, 5, 12, 52, 191, 211, 220 Hepatic Duct, Common, 211, 220 Hepatitis, 5, 152, 153, 220 Hepatocellular, 37, 52, 68, 220 Hepatocellular carcinoma, 52, 68, 220 Hepatocyte, 12, 37, 53, 220 Hepatoma, 11, 220 Hereditary, 42, 220, 255 Heredity, 216, 217, 220 Herpes, 36, 149, 220 Herpes Zoster, 220 Heterogeneity, 34, 190, 220 Hippocampus, 26, 207, 220, 245, 254 Histiocytosis, 78, 85, 220 Histocompatibility, 153, 220 Histology, 3, 10, 12, 20, 41, 45, 79, 87, 100, 114, 137, 148, 152, 220, 238 Histones, 202, 220 Homeobox, 23, 30, 220 Homeostasis, 49, 220 Homologous, 191, 205, 206, 216, 221, 244, 250, 254 Hormonal, 23, 45, 221 Hormone, 97, 190, 216, 221, 224, 225, 231, 243, 248, 255, 256 Hormone Replacement Therapy, 97, 221 Hormone therapy, 190, 221

Human papillomavirus, 10, 22, 24, 37, 41, 50, 61, 64, 66, 77, 80, 96, 98, 100, 221 Humoral, 17, 218, 221 Humour, 221 Hybrid, 15, 70, 80, 195, 203, 221 Hydrocephalus, 49, 221, 225 Hydrogen, 189, 199, 207, 213, 221, 228, 233, 235, 237, 240, 244 Hydrolysis, 148, 197, 221, 226, 244 Hyperaemia, 205, 221 Hypercalciuria, 154, 221 Hyperplasia, 13, 21, 23, 84, 87, 221 Hypersensitivity, 11, 191, 208, 221, 248 Hypertension, 199, 221, 225 Hypertrophy, 196, 221 Hypoxia, 19, 222 Hysterectomy, 81, 161, 222 I Image Cytometry, 12, 162, 222 Immaturity, 45, 222 Immersion, 132, 222 Immune function, 45, 222 Immune response, 27, 33, 37, 153, 190, 193, 218, 219, 222, 229, 254, 259, 260 Immune system, 37, 193, 196, 222, 229, 260 Immunochemistry, 212, 222 Immunodeficiency, 37, 152, 159, 222 Immunodeficiency syndrome, 159, 222 Immunofluorescence, 33, 67, 126, 222 Immunogenic, 222, 228 Immunoglobulin, 154, 193, 222, 233 Immunohistochemistry, 12, 53, 54, 137, 222 Immunologic, 10, 20, 45, 148, 202, 222, 246 Immunologic Factors, 46, 222 Immunology, 14, 17, 38, 89, 190, 215, 222 Immunophenotyping, 21, 99, 222 Immunosuppressant, 215, 222 Immunosuppression, 153, 222, 223, 229, 236 Immunosuppressive, 152, 153, 222, 254 Immunosuppressive Agents, 152, 153, 222 Implant radiation, 223, 224, 226, 245, 261 In situ, 12, 16, 19, 20, 23, 50, 54, 88, 137, 148, 149, 223 In Situ Hybridization, 12, 16, 20, 23, 54, 88, 137, 149, 223 In vitro, 5, 8, 12, 23, 27, 37, 39, 49, 216, 223, 241, 250, 254 In vivo, 7, 17, 23, 28, 33, 47, 49, 55, 210, 216, 223, 229, 254 Incidental, 66, 223

270

Cytology

Incision, 157, 223, 225 Incisional, 157, 223 Incisional biopsy, 157, 223 Incontinence, 221, 223 Indinavir, 99, 223 Induction, 26, 54, 153, 223 Infant, Newborn, 191, 223 Infarction, 8, 83, 206, 221, 223, 231 Infertility, 223, 259 Infiltration, 217, 223 Informed Consent, 13, 20, 224 Infusion, 52, 224 Ingestion, 219, 224, 231 Inhalation, 194, 219, 224 Initiation, 40, 224, 257 Inorganic, 123, 224, 233 Insertional, 29, 224 Insight, 10, 11, 21, 24, 224 Insulin, 29, 42, 47, 224, 226 Insulin-dependent diabetes mellitus, 224 Intercellular Junctions, 27, 224 Interferon, 18, 224 Interferon-alpha, 224 Interleukins, 223, 224 Intermittent, 38, 224 Internal radiation, 224, 226, 245, 261 Interneurons, 26, 224 Interspecific, 224, 225 Interstitial, 154, 155, 175, 198, 214, 224, 225, 226, 261 Intestinal, 200, 202, 225 Intestine, 196, 198, 203, 225, 227 Intoxication, 225, 260 Intracellular, 25, 38, 55, 57, 217, 223, 225, 230, 235, 242, 248 Intracellular Membranes, 225, 230 Intracranial Hemorrhages, 221, 225 Intracranial Hypertension, 219, 221, 225 Intraepithelial, 69, 225 Intraperitoneal, 72, 225 Intrathecal, 35, 225 Intrathecal chemotherapy, 35, 225 Intravenous, 10, 36, 113, 154, 155, 174, 176, 224, 225 Intravenous pyelogram, 154, 155, 174, 176, 225 Intrinsic, 29, 134, 190, 196, 225 Introgression, 15, 225 Intubation, 200, 225 Invalidate, 127, 225 Invasive, 9, 13, 21, 22, 44, 47, 50, 52, 55, 133, 136, 140, 141, 175, 225, 229, 244

Invasive cervical cancer, 22, 141, 225 Iodine, 35, 225, 251 Iodine-131, 35, 225 Ion Transport, 49, 225 Ions, 27, 189, 208, 210, 221, 225, 226, 232 Iris, 205, 226, 245 Irradiation, 35, 36, 226, 261 Ischemia, 49, 54, 226 K Kb, 15, 168, 226 Keratoconus, 87, 226 Ketoacidosis, 189, 226 Ketone Bodies, 189, 226 Kidney Disease, 154, 155, 168, 226 Kidney Failure, 212, 226 Kidney Pelvis, 226, 258 Kidney stone, 155, 226, 258 Kidney Transplantation, 153, 156, 227 Kinetic, 227 Kinetochores, 24, 227 L Labile, 203, 227 Lag, 8, 227 Laminin, 196, 214, 227 Laparoscopy, 155, 227 Large Intestine, 203, 208, 225, 227, 246, 251 Laryngeal, 50, 227 Larynx, 121, 141, 227, 256 Latent, 227, 242 Lavage, 84, 98, 102, 227 Lectin, 227, 231 Lens, 110, 227, 260 Lesion, 4, 13, 22, 42, 44, 45, 157, 218, 227, 228, 250, 258 Lethal, 8, 38, 227 Lethargy, 221, 227 Leucocyte, 227 Leukaemia, 122, 142, 227 Leukemia, 54, 216, 227 Leukocytes, 33, 89, 196, 198, 202, 212, 224, 227, 235 Life cycle, 29, 108, 215, 227 Ligament, 63, 214, 228, 243 Ligands, 8, 26, 200, 228 Light microscope, 54, 228 Linkage, 42, 228 Lipid, 38, 94, 224, 228, 237 Lipid A, 38, 228 Lipid Peroxidation, 228, 237 Lipopolysaccharides, 228 Lithotripsy, 53, 228

271

Liver, 5, 12, 19, 36, 52, 71, 99, 189, 191, 196, 207, 208, 210, 216, 217, 220, 228, 243, 249 Liver metastases, 52, 228 Liver scan, 228, 249 Localization, 9, 24, 26, 28, 36, 39, 54, 222, 228 Localized, 28, 38, 116, 210, 215, 223, 227, 228, 240, 241, 258 Locoregional, 35, 228 Longitudinal Studies, 23, 228 Long-Term Potentiation, 26, 228 Loop, 52, 68, 86, 228 Loss of Heterozygosity, 88, 228 Luciferase, 5, 229 Lymph, 69, 90, 103, 121, 123, 137, 141, 152, 163, 195, 201, 211, 221, 229, 238, 250, 254 Lymph node, 90, 103, 121, 123, 137, 141, 152, 163, 195, 201, 229, 238, 250, 254 Lymphadenopathy, 69, 229 Lymphatic, 33, 192, 211, 223, 229, 231, 241, 252, 255 Lymphatic system, 192, 229, 252, 255 Lymphocyte, 37, 45, 193, 222, 229 Lymphocyte Depletion, 222, 229 Lymphoid, 55, 193, 227, 229 Lymphoma, 64, 73, 75, 77, 87, 90, 99, 122, 142, 192, 229 M Macrophage, 17, 229 Magnetic Resonance Imaging, 154, 156, 210, 229, 249 Major Histocompatibility Complex, 219, 229 Malformation, 219, 229 Malignancy, 22, 59, 79, 84, 97, 101, 111, 157, 186, 229, 238 Malignant mesothelioma, 229, 231 Malignant tumor, 81, 199, 230, 248 Mammary, 74, 78, 87, 230 Mammogram, 230, 232 Mandible, 191, 230, 247 Manifest, 9, 230 Mannans, 216, 230 Mastitis, 74, 230 Matrix metalloproteinase, 12, 230 Meatus, 156, 230 Mediate, 23, 26, 200, 230 Medical Errors, 32, 230 Medical Records, 230, 248 Medication Errors, 230 MEDLINE, 169, 230 Meiosis, 24, 40, 202, 230, 232, 254

Melanocytes, 230 Melanoma, 27, 68, 93, 230 Membrane Proteins, 36, 39, 230 Memory, 134, 228, 231 Menarche, 231, 247 Meninges, 35, 201, 206, 231 Menopause, 231, 242, 247 Menstruation, 231, 247 Mental, iv, 4, 168, 170, 208, 209, 214, 231, 245, 249 Mental Health, iv, 4, 168, 170, 231, 245 Mercury, 215, 231 Mesenchymal, 10, 23, 231 Mesoderm, 49, 231 Mesothelioma, 63, 71, 230, 231 Metabolite, 34, 123, 197, 231, 243 Metaphase, 25, 227, 231 Metaplasia, 21, 48, 231 Metastasis, 12, 35, 39, 47, 63, 68, 90, 91, 96, 100, 200, 230, 231 Metastatic, 21, 33, 62, 121, 141, 198, 231, 249 Methacrylate, 16, 231 Methanol, 148, 231 MI, 40, 60, 187, 231 Microbe, 231, 256 Microbiology, 58, 77, 135, 190, 195, 231 Microcalcifications, 99, 232 Micromanipulators, 124, 232 Micronuclei, 89, 232 Microorganism, 203, 232, 260 Microtubules, 24, 201, 227, 232 Migration, 12, 33, 232 Milliliter, 113, 232 Millimeter, 35, 232 Mitochondria, 232, 237 Mitochondrial Swelling, 232, 234 Mitosis, 24, 194, 202, 232 Mitotic, 227, 232 Mobilization, 11, 232 Modeling, 25, 35, 52, 232 Modification, 25, 52, 192, 217, 232 Molecular Evolution, 15, 232 Molecular Structure, 15, 232 Monitor, 33, 40, 126, 128, 233, 235 Monoclonal, 35, 226, 233, 245, 261 Monoclonal antibodies, 35, 233 Monocyte, 18, 233 Monosomy, 193, 233 Morphological, 16, 17, 20, 33, 88, 148, 210, 216, 230, 233

272

Cytology

Morphology, 20, 28, 33, 61, 67, 72, 107, 115, 126, 147, 148, 149, 154, 156, 194, 219, 233 Motility, 233 Motor Activity, 28, 233 Mucinous, 75, 233 Mucins, 217, 233, 249 Mucolytic, 198, 233 Mucosa, 72, 132, 233 Mucus, 41, 213, 233, 258 Multivariate Analysis, 48, 233 Muscle Fibers, 191, 233, 234 Mutagenesis, 7, 12, 29, 51, 89, 233 Mutagens, 233 Mycophenolate mofetil, 153, 233 Mycosis, 233, 238 Mydriatic, 208, 233 Myocardium, 231, 233 Myosin, 28, 234 N Necrosis, 54, 154, 194, 223, 231, 234, 248 Needle biopsy, 65, 214, 234 Neonatal, 23, 234 Neoplasia, 3, 12, 24, 37, 40, 41, 44, 61, 77, 81, 85, 98, 102, 234, 244 Neoplasm, 71, 219, 234, 238, 249, 258 Neoplastic, 20, 73, 121, 141, 142, 192, 228, 229, 234, 236 Neostriatum, 54, 200, 206, 234, 245 Nephropathy, 154, 226, 234 Nerve, 7, 28, 192, 195, 207, 214, 234, 236, 242, 253, 257, 259 Nervous System, 20, 201, 234, 235, 239 Networks, 52, 222, 234, 255 Neural, 6, 35, 192, 221, 222, 234 Neuroblastoma, 67, 234 Neuroectodermal tumor, 93, 234 Neuroendocrine, 62, 234 Neurologic, 221, 234 Neurology, 152, 234 Neuromuscular, 7, 189, 234 Neuromuscular Junction, 7, 189, 234 Neuronal, 26, 48, 234 Neurons, 26, 207, 213, 216, 224, 234, 245, 254 Neuropeptides, 49, 234 Neurophysiology, 43, 207, 234 Neuropsychology, 35, 234 Neurotoxicity, 35, 235 Neurotransmitter, 189, 192, 198, 200, 217, 235, 254 Neutralization, 18, 235

Neutrons, 191, 226, 235, 245 Neutrophils, 146, 227, 235 Nipple discharge, 76, 83, 235 Nitric Oxide, 49, 235 Nitrogen, 57, 213, 215, 235 Non-small cell lung cancer, 21, 84, 235 Nuclear, 35, 40, 54, 56, 65, 69, 95, 129, 154, 195, 210, 213, 216, 234, 235, 236, 244 Nuclear Matrix, 65, 95, 235 Nuclear Pore, 235 Nuclei, 112, 125, 129, 134, 191, 210, 216, 217, 220, 229, 232, 235, 236, 244, 255 Nucleic acid, 9, 148, 207, 216, 223, 233, 235 Nucleolus, 235, 236, 248 O Obstetrics, 24, 59, 65, 66, 67, 68, 76, 81, 86, 91, 136, 143, 236 Ocular, 76, 82, 90, 236 Odds Ratio, 236, 247 Ointments, 236, 238 Omentum, 94, 236 Oncogenes, 13, 21, 236, 244 Oncogenic, 10, 22, 51, 236, 242 Oncogenic Viruses, 236, 242 Oncologist, 41, 236 On-line, 55, 185, 236 Opacity, 207, 236 Ophthalmology, 95, 215, 236 Opportunistic Infections, 44, 236 Optic Nerve, 236, 247 Oral Health, 236, 237 Oral Hygiene, 152, 175, 236 Orbit, 95, 237 Orbital, 28, 237 Orderly, 54, 202, 237 Organelles, 49, 201, 207, 230, 237, 241 Orofacial, 151, 237 Osteoblasts, 237 Osteocytes, 25, 237 Osteoporosis, 26, 237 Outpatient, 130, 237 Ovaries, 218, 237, 247 Ovary, 84, 237 Ovum, 217, 227, 237, 243 Oxidation, 194, 197, 228, 237 Oxidative Stress, 13, 237 P P53 gene, 12, 42, 48, 237 Palliative, 237, 255 Pancreas, 71, 74, 75, 88, 92, 189, 197, 208, 224, 237, 238, 258

273

Pancreatic, 92, 98, 111, 116, 133, 162, 211, 237, 238 Pancreatic cancer, 92, 162, 237 Pancreatic Ducts, 116, 133, 211, 237 Pancreatic Juice, 237, 238 Pancreatitis, 196, 238 Pap test, 33, 100, 116, 132, 238 Papilla, 211, 238 Papillary, 61, 74, 84, 91, 154, 238 Papilloma, 45, 50, 98, 117, 141, 149, 238 Papillomavirus, 37, 96, 238 Papovaviridae, 238, 242 Paracoccidioidomycosis, 91, 238 Paracrine Communication, 23, 238 Paraffin, 16, 32, 115, 137, 238 Parasite, 13, 238 Parenchyma, 12, 238 Parietal, 238, 239, 241 Parotid, 68, 91, 101, 238 Parthenogenesis, 7, 238 Particle, 238, 257 Parturition, 236, 238 Pathogenesis, 10, 21, 27, 46, 238 Pathologic, 20, 23, 25, 114, 157, 194, 197, 199, 205, 215, 221, 238, 239, 244, 247, 256 Pathologic Processes, 194, 239 Pathologies, 76, 239 Pathologist, 4, 24, 32, 126, 137, 239 Patient Education, 174, 176, 180, 182, 187, 239 Patient Selection, 13, 239 Pelvic, 92, 101, 144, 152, 155, 239, 243 Pelvis, 189, 237, 239, 259 Peptide, 18, 49, 191, 202, 211, 214, 239, 244, 256 Perception, 205, 239, 249 Percutaneous, 228, 239 Perforation, 116, 215, 239 Perfusion, 28, 34, 222, 239 Pericytes, 16, 239 Perioral, 152, 239 Peripheral blood, 46, 224, 239 Peripheral Nervous System, 234, 235, 239, 243, 254 Peritoneal, 69, 76, 78, 92, 94, 100, 194, 195, 225, 239 Peritoneal Cavity, 194, 195, 225, 239 Peritoneal Lavage, 94, 239 Peritoneum, 236, 239, 248 Pesticide Residues, 123, 240 Petroleum, 238, 240 PH, 12, 55, 154, 240

Phallic, 215, 240 Pharmacokinetic, 240 Pharmacologic, 192, 240, 256 Phenotype, 6, 9, 25, 240 Phosphorus, 198, 240 Photodynamic therapy, 12, 240 Photosensitizer, 36, 240 Physical Examination, 154, 155, 175, 240 Physiologic, 197, 231, 240, 246, 247 Physiology, 10, 26, 38, 190, 210, 211, 218, 219, 234, 240 Pigment, 230, 240 Pilot Projects, 15, 43, 240 Pilot study, 42, 240 Pipette, 125, 134, 240 Pituitary Gland, 214, 240 Plague, 43, 240 Plants, 198, 199, 217, 227, 233, 240, 249, 252, 256, 257 Plaque, 135, 241 Plasma, 24, 38, 191, 193, 200, 211, 217, 219, 220, 226, 241, 246, 250, 260 Plasma cells, 193, 241 Plasticity, 26, 241 Plastids, 237, 241 Platelet Aggregation, 192, 235, 241 Platelets, 235, 241 Platinum, 228, 241 Pleura, 102, 241 Pleural, 63, 71, 84, 102, 185, 241 Plexus, 48, 241 Ploidy, 12, 18, 48, 126, 241 Pneumonia, 205, 241 Point Mutation, 12, 241 Polyethylene, 148, 241 Polymerase, 5, 39, 100, 241 Polymerase Chain Reaction, 100, 241 Polymorphic, 202, 207, 242 Polymorphism, 12, 15, 42, 51, 242 Polyomavirus, 99, 238, 242 Polyposis, 203, 242 Polysaccharide, 193, 201, 218, 242, 244 Port, 120, 242 Port-a-cath, 242 Posterior, 192, 195, 196, 201, 202, 226, 237, 242 Postmenopausal, 62, 97, 237, 242 Postnatal, 242, 253 Postsynaptic, 7, 242 Post-translational, 25, 242 Potassium, 155, 242 Practice Guidelines, 170, 176, 242

274

Cytology

Precancerous, 141, 143, 175, 202, 242 Precursor, 21, 22, 34, 44, 49, 138, 209, 212, 242, 243, 244 Premalignant, 242, 243 Prenatal, 210, 242 Preoperative, 69, 242 Presynaptic, 7, 26, 235, 243 Presynaptic Terminals, 26, 243 Prevalence, 10, 13, 31, 42, 44, 127, 236, 243 Primary Sclerosing Cholangitis, 95, 101, 243 Primary tumor, 243, 250 Probe, 34, 55, 77, 243 Prodrug, 53, 243 Progeny, 6, 43, 243 Progesterone, 243, 253 Progression, 12, 21, 22, 24, 29, 37, 39, 44, 48, 50, 51, 54, 193, 243, 260 Progressive, 14, 200, 203, 209, 213, 234, 243, 258 Projection, 224, 236, 243, 245 Promoter, 12, 22, 243 Prophase, 40, 243, 254 Prophylaxis, 159, 243, 248, 259 Prospective study, 45, 59, 67, 243 Prostate, 21, 23, 46, 123, 154, 176, 196, 197, 243, 244, 247, 258 Prostate gland, 23, 243 Prostatic Hyperplasia, 243 Prostatic Intraepithelial Neoplasia, 47, 243 Prostatitis, 152, 244 Protease, 5, 44, 223, 244 Protease Inhibitors, 44, 244 Protein Binding, 54, 244 Protein C, 8, 9, 24, 52, 54, 191, 192, 195, 244 Protein Kinases, 236, 244 Protein S, 53, 197, 216, 244, 248 Proteoglycans, 196, 214, 244 Proteolytic, 39, 204, 244 Protocol, 12, 14, 35, 244 Protons, 191, 221, 244, 245 Proto-Oncogenes, 236, 244 Protozoa, 232, 244, 252, 259 Psoriasis, 244, 248 Psychiatry, 13, 214, 244 Psychoactive, 245, 255, 260 Psychology, 209, 234, 245 Psychophysiology, 235, 245 Public Health, 13, 15, 31, 41, 42, 43, 170, 245 Public Policy, 169, 245 Puerperium, 236, 245

Pulmonary, 19, 38, 75, 93, 98, 135, 152, 197, 198, 226, 245, 259 Pulmonary hypertension, 19, 245 Pulse, 233, 245 Pupil, 205, 208, 233, 245 Putamen, 206, 234, 245 Pyramidal Cells, 207, 245 R Race, 232, 245 Radiation oncologist, 236, 245 Radiation therapy, 175, 176, 189, 190, 213, 215, 224, 226, 245, 261 Radioactive, 195, 198, 221, 223, 224, 225, 226, 228, 233, 235, 236, 245, 246, 249, 251, 261 Radiography, 154, 175, 205, 245 Radiolabeled, 198, 226, 245, 261 Radiology, 65, 70, 246 Radiolucent, 157, 246 Radiopharmaceutical, 35, 246 Radiotherapy, 198, 226, 245, 246, 253, 261 Randomized, 12, 22, 36, 41, 95, 210, 246 Reagent, 51, 229, 246 Receptor, 9, 18, 23, 26, 54, 81, 190, 193, 205, 246 Recombinant, 5, 27, 52, 246, 259 Recombination, 40, 216, 246 Reconstitution, 55, 246 Rectal, 21, 246 Rectum, 194, 198, 203, 208, 216, 223, 227, 243, 246 Recur, 175, 246 Recurrence, 21, 39, 63, 92, 95, 99, 202, 246 Refer, 1, 152, 203, 215, 220, 224, 228, 235, 246, 256 Reference point, 46, 246 Reflex, 214, 246 Reflux, 27, 246 Refraction, 246, 251 Regeneration, 30, 191, 214, 246 Regimen, 209, 246 Regurgitation, 219, 246 Relapse, 28, 247 Relative risk, 21, 50, 189, 247 Reliability, 33, 129, 143, 247 Remission, 246, 247 Renal cysts, 154, 247 Renal pelvis, 226, 247, 257 Replicon, 5, 247 Reproductive History, 24, 247 Reproductive system, 243, 247 Resection, 4, 92, 156, 162, 247

275

Residual disease, 68, 247 Resorption, 25, 221, 247 Respiration, 199, 232, 233, 247 Response rate, 52, 247 Retina, 6, 202, 227, 236, 247, 248, 260 Retinal, 205, 236, 248 Retinoids, 152, 248 Retrograde, 112, 133, 248 Retroperitoneal, 101, 248 Retrospective, 3, 63, 248 Retrospective study, 63, 248 Retroviral vector, 216, 248 Reverse Transcriptase Polymerase Chain Reaction, 45, 248 Rhabdomyosarcoma, 93, 248 Rheumatism, 248 Rheumatoid, 75, 248 Rheumatoid arthritis, 248 Rheumatoid Nodule, 75, 248 Ribosome, 248, 257 Rickettsiae, 248, 259 Risk factor, 13, 32, 50, 176, 243, 247, 248 Rubber, 124, 189, 248 S Saline, 198, 249 Saliva, 120, 249 Salivary, 61, 67, 95, 96, 207, 208, 214, 237, 249 Salivary glands, 207, 208, 214, 249 Saponins, 249, 253 Sarcoma, 74, 75, 97, 121, 122, 141, 142, 249 Scans, 118, 154, 156, 249 Scatter, 146, 249 Schizoid, 249, 260 Schizophrenia, 42, 249, 260 Schizotypal Personality Disorder, 249, 260 Secondary tumor, 231, 249 Secretion, 9, 49, 221, 224, 233, 249, 250, 259 Secretory, 12, 244, 249 Sediment, 13, 81, 88, 131, 249, 250, 258 Sedimentation, 201, 250, 257 Segmental, 9, 250 Segmentation, 250 Segregation, 24, 40, 42, 195, 202, 246, 250 Self Care, 155, 250 Semen, 120, 154, 210, 243, 250 Seminiferous Epithelium, 107, 250 Seminiferous tubule, 250, 252 Senile, 237, 250 Sensor, 8, 250 Sentinel lymph node, 82, 83, 86, 250 Sequencing, 12, 15, 16, 18, 48, 242, 250

Serology, 42, 250 Serous, 195, 211, 241, 250 Serum, 77, 121, 141, 142, 191, 192, 203, 229, 246, 250 Sex Ratio, 15, 250 Sexually Transmitted Diseases, 143, 250 Shedding, 33, 250 Shock, 53, 176, 228, 250, 257 Side effect, 35, 159, 190, 197, 250, 256 Signs and Symptoms, 175, 247, 250 Skull, 206, 237, 250, 255 Small cell lung cancer, 21, 250 Small intestine, 176, 209, 211, 221, 225, 251, 260 Smallpox, 251, 259 Smoking Cessation, 41, 251 Smooth muscle, 9, 53, 192, 239, 251, 254 Sneezing, 250, 251 Sodium, 12, 35, 251, 254 Sodium Iodide, 35, 251 Soft tissue, 70, 81, 123, 151, 157, 198, 251 Solvent, 123, 189, 231, 251 Soma, 245, 251 Somatic, 40, 221, 230, 232, 239, 251, 255 Somatic cells, 40, 230, 232, 251 Space Flight, 26, 251 Specialist, 53, 152, 178, 208, 251 Specificity, 4, 34, 48, 53, 126, 131, 190, 211, 251 Spectrometer, 56, 251 Spectroscopic, 56, 251 Spectrum, 14, 57, 88, 251 Speculum, 117, 144, 252 Sperm, 125, 202, 250, 252, 257 Spermatogenesis, 15, 94, 107, 252 Spermatozoa, 250, 252 Sphincter, 138, 227, 252 Spinal cord, 35, 201, 202, 225, 231, 234, 239, 246, 252 Spleen, 78, 96, 207, 229, 252 Spontaneous Abortion, 24, 252 Spores, 107, 252 Sputum, 21, 64, 97, 143, 162, 185, 252 Squamous, 10, 12, 44, 45, 61, 67, 69, 86, 98, 102, 132, 146, 212, 235, 252 Squamous cell carcinoma, 61, 102, 212, 235, 252 Squamous cells, 132, 252 Squamous Epithelium, 12, 252 Squamous intraepithelial lesion, 86, 252 Stabilization, 157, 252 Staging, 20, 84, 249, 252

276

Cytology

Standard therapy, 46, 252 Standardize, 52, 252 Steel, 89, 252 Stem Cells, 49, 218, 253 Stenosis, 253 Stent, 111, 133, 253 Stereotactic, 65, 253 Sterility, 15, 223, 253 Steroid, 23, 196, 249, 253 Stimulants, 13, 253 Stimulus, 38, 205, 209, 210, 213, 227, 246, 253, 255 Stomach, 116, 138, 176, 189, 208, 213, 216, 221, 227, 236, 239, 246, 251, 252, 253 Stool, 203, 223, 227, 253 Strand, 12, 241, 253 Stress, 4, 38, 43, 126, 155, 175, 237, 248, 249, 253 Stria, 89, 253 Striatum, 234, 253 Stricture, 83, 111, 116, 253 Stroke, 168, 199, 253 Stroma, 39, 226, 238, 253 Stromal, 20, 23, 61, 87, 253 Styrene, 249, 253 Subacute, 223, 253 Subclinical, 223, 253 Subcutaneous, 209, 248, 253, 261 Subiculum, 220, 254 Subspecies, 251, 254, 259 Substance P, 231, 246, 249, 254 Substrate, 34, 134, 147, 254 Suction, 7, 144, 254 Suppression, 10, 26, 254 Supraclavicular, 98, 254 Supraclavicular lymph nodes, 98, 254 Sweat, 254 Sweat Glands, 254 Symphysis, 243, 254 Synapse, 7, 191, 234, 243, 254, 257 Synaptic, 7, 191, 228, 235, 254 Synergistic, 21, 254 Synovial, 97, 119, 254 Synovial Fluid, 119, 254 Synovial Membrane, 254 Syringoma, 68, 254 Systemic, 27, 36, 45, 52, 197, 199, 223, 225, 226, 245, 254, 259, 261 T Tacrolimus, 153, 254 Technology Transfer, 14, 254 Telecommunications, 204, 255

Telencephalon, 195, 255 Telomerase, 73, 87, 255 Telophase, 232, 255 Temporal, 23, 44, 220, 230, 255 Tendon, 75, 255 Tetrahydrocannabinol, 199, 255 Thalassemia, 196, 255 Therapeutics, 14, 255 Thermal, 194, 209, 235, 241, 255 Thoracic, 84, 101, 102, 208, 229, 241, 255, 260 Threshold, 130, 131, 213, 221, 255 Thrombin, 241, 244, 255 Thrombomodulin, 244, 255 Thrombosis, 244, 253, 255 Thrush, 199, 255 Thymus, 229, 255 Thyroid Gland, 61, 218, 255, 256 Thyroid Hormones, 255, 256 Thyroid Neoplasms, 59, 79, 81, 256 Thyroid Nodule, 72, 75, 94, 256 Thyrotropin, 77, 256 Thyroxine, 191, 256 Tissue Fixation, 115, 256 Tolerance, 26, 153, 160, 190, 217, 256 Tomography, 256 Tone, 237, 256 Topical, 36, 152, 238, 256 Toxic, iv, 73, 231, 253, 256 Toxicity, 27, 35, 209, 231, 256 Toxicokinetics, 256 Toxicology, 14, 43, 170, 256 Toxin, 28, 39, 123, 212, 256 Trace element, 202, 256 Trachea, 198, 213, 227, 255, 256 Transcriptase, 73, 255, 256 Transcription Factors, 54, 236, 257 Transduction, 38, 52, 257 Transfection, 9, 39, 54, 197, 216, 257 Transgenes, 15, 17, 257 Transitional cell carcinoma, 64, 88, 154, 257 Transitional cells, 11, 257 Translation, 11, 31, 191, 257 Translational, 20, 257 Transmitter, 189, 257 Transplantation, 70, 88, 153, 155, 203, 229, 257 Transurethral, 92, 174, 257 Transurethral resection, 92, 174, 257 Trauma, 213, 234, 238, 239, 257 Trees, 248, 257

277

Triage, 46, 78, 93, 98, 257 Trisomy, 193, 257 Tuberculosis, 76, 78, 257 Tuberous Sclerosis, 29, 257 Tubulin, 232, 257 Tumor marker, 197, 257 Tumor suppressor gene, 12, 21, 51, 228, 237, 258 Tumour, 63, 102, 258 Tunica, 233, 258 U Ubiquitin, 11, 258 Ulcer, 4, 258 Ulceration, 152, 258 Ulcerative colitis, 243, 258 Ultrasonography, 68, 102, 258 Urban Population, 65, 258 Ureter, 156, 226, 228, 247, 257, 258 Ureteroscope, 156, 258 Ureteroscopy, 156, 258 Urethra, 101, 196, 243, 257, 258 Uric, 154, 258 Urinalysis, 130, 154, 155, 176, 258 Urinary tract, 111, 121, 141, 154, 155, 195, 258, 259 Urinate, 258, 260 Urine, 13, 35, 39, 60, 64, 70, 72, 81, 88, 96, 100, 120, 121, 126, 130, 141, 142, 143, 154, 155, 156, 162, 163, 174, 175, 176, 185, 186, 195, 196, 197, 219, 221, 223, 225, 226, 247, 258 Urodynamic, 155, 175, 258 Urogenital, 218, 258 Urolithiasis, 154, 258 Urology, 23, 39, 79, 88, 95, 96, 101, 136, 154, 258 Urothelium, 13, 259 Uterus, 201, 206, 211, 218, 222, 231, 237, 243, 247, 259 V Vaccination, 37, 259 Vaccines, 27, 42, 259, 260 Vaccinia, 27, 259 Vaccinia Virus, 27, 259 Vacuoles, 237, 259 Vagina, 143, 144, 187, 199, 201, 203, 218, 231, 247, 259

Vaginal, 117, 128, 140, 143, 144, 152, 155, 159, 161, 259 Vaginal Discharge, 152, 259 Vaginitis, 199, 259 Vaginosis, 45, 152, 259 Variola, 259 Vascular, 33, 44, 53, 156, 202, 211, 223, 235, 255, 259 Vasodilators, 235, 259 Vector, 5, 17, 57, 224, 257, 259 Vein, 225, 235, 238, 259 Venous, 220, 244, 259 Ventricle, 200, 220, 245, 259 Ventricular, 221, 259 Venules, 197, 199, 211, 259 Vertebrae, 252, 259 Veterinary Medicine, 169, 259 Vibrio, 38, 202, 260 Villi, 221, 260 Viral, 4, 5, 17, 24, 39, 42, 45, 50, 51, 149, 236, 244, 257, 260 Viral Load, 24, 45, 50, 51, 260 Virulence, 38, 195, 256, 260 Viscera, 251, 260 Visceral, 83, 102, 239, 260 Vitreous, 227, 247, 260 Vitreous Body, 247, 260 Vitro, 124, 125, 260 Vivo, 33, 229, 260 Void, 155, 260 W Warts, 221, 260 White blood cell, 193, 227, 229, 233, 241, 260 Windpipe, 198, 255, 260 Withdrawal, 116, 260 Wound Healing, 30, 47, 200, 214, 230, 260 X Xenograft, 193, 260 X-ray, 30, 162, 186, 204, 205, 211, 215, 216, 225, 226, 230, 235, 245, 246, 249, 253, 260 X-ray therapy, 226, 260 Y Yeasts, 199, 215, 216, 240, 261 Z Zebrafish, 6, 261 Zygomycosis, 76, 261 Zymogen, 244, 261

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