HUMAN
PAPILLOMA VIRUS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , 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 ©2003 by ICON Group International, Inc. Copyright ©2003 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., 1960Human Papilloma Virus: 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: 0-597-83932-8 1. Human Papilloma Virus-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.
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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 human papilloma virus. 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 HUMAN PAPILLOMA VIRUS ..................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Human Papilloma Virus............................................................... 4 E-Journals: PubMed Central ....................................................................................................... 30 The National Library of Medicine: PubMed ................................................................................ 31 CHAPTER 2. NUTRITION AND HUMAN PAPILLOMA VIRUS ........................................................... 79 Overview...................................................................................................................................... 79 Finding Nutrition Studies on Human Papilloma Virus.............................................................. 79 Federal Resources on Nutrition ................................................................................................... 81 Additional Web Resources ........................................................................................................... 82 CHAPTER 3. ALTERNATIVE MEDICINE AND HUMAN PAPILLOMA VIRUS ..................................... 83 Overview...................................................................................................................................... 83 National Center for Complementary and Alternative Medicine.................................................. 83 Additional Web Resources ........................................................................................................... 90 General References ....................................................................................................................... 91 CHAPTER 4. DISSERTATIONS ON HUMAN PAPILLOMA VIRUS ....................................................... 93 Overview...................................................................................................................................... 93 Dissertations on Human Papilloma Virus .................................................................................. 93 Keeping Current .......................................................................................................................... 93 CHAPTER 5. PATENTS ON HUMAN PAPILLOMA VIRUS .................................................................. 95 Overview...................................................................................................................................... 95 Patents on Human Papilloma Virus............................................................................................ 95 Patent Applications on Human Papilloma Virus ...................................................................... 118 Keeping Current ........................................................................................................................ 129 CHAPTER 6. BOOKS ON HUMAN PAPILLOMA VIRUS ................................................................... 131 Overview.................................................................................................................................... 131 Book Summaries: Federal Agencies............................................................................................ 131 Book Summaries: Online Booksellers......................................................................................... 132 The National Library of Medicine Book Index ........................................................................... 133 Chapters on Human Papilloma Virus........................................................................................ 133 CHAPTER 7. MULTIMEDIA ON HUMAN PAPILLOMA VIRUS ......................................................... 135 Overview.................................................................................................................................... 135 Video Recordings ....................................................................................................................... 135 Audio Recordings....................................................................................................................... 136 CHAPTER 8. PERIODICALS AND NEWS ON HUMAN PAPILLOMA VIRUS ...................................... 139 Overview.................................................................................................................................... 139 News Services and Press Releases.............................................................................................. 139 Academic Periodicals covering Human Papilloma Virus .......................................................... 141 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 145 Overview.................................................................................................................................... 145 NIH Guidelines.......................................................................................................................... 145 NIH Databases........................................................................................................................... 147 Other Commercial Databases..................................................................................................... 150 APPENDIX B. PATIENT RESOURCES ............................................................................................... 151 Overview.................................................................................................................................... 151 Patient Guideline Sources.......................................................................................................... 151 Finding Associations.................................................................................................................. 156 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 159 Overview.................................................................................................................................... 159
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Preparation................................................................................................................................. 159 Finding a Local Medical Library................................................................................................ 159 Medical Libraries in the U.S. and Canada ................................................................................. 159 ONLINE GLOSSARIES................................................................................................................ 165 Online Dictionary Directories ................................................................................................... 165 HUMAN PAPILLOMA VIRUS DICTIONARY....................................................................... 167 INDEX .............................................................................................................................................. 229
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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 human papilloma virus 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 human papilloma virus, 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 human papilloma virus, 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 human papilloma virus. 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 human papilloma virus, 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 human papilloma virus. 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 HUMAN PAPILLOMA VIRUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on human papilloma virus.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and human papilloma virus, 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 “human papilloma virus” (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: •
HIV - Positive Women and Their Care Source: Positively Aware; Jan./Feb. 1996. Contact: Test Positive Aware Network, 5537 N Broadway, Chicago, IL, 60640, (773) 9899400, http://www.tpan.com. Summary: This article considers the incidence of HIV among women and highlights the importance of regular gynecological examinations to detect HIV and female-specific conditions. The author explains that, following an initial examination, an HIV-positive woman should undergo the same tests as a man to determine where she stands in the course of HIV progression. Complications and treatment are addressed, including vaginal candidiasis, human papilloma virus, cervical cancer, and menstrual problems.
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All women are advised to have regular Pap smears, pelvic exams, and a general gynecological assessment. •
Vulvar Squamous Cell Carcinoma Source: Seminars in Dermatology. 15(1):51-59; March 1996. Summary: This journal article for health professionals presents an overview of vulvar squamous cell carcinoma. The epidemiological aspects and risk factors of squamous cell carcinoma of the vulva are examined. Risk factors include a history of human papilloma virus infection and gonorrhea, smoking, vulvar intraepithelial neoplasia, and vulvar dystrophies. The clinical presentation of vulvar cancer is described, including pruritus, the presence of a vulvar mass, local discomfort, discharge and bleeding, and groin mass. Guidelines for pretreatment assessment are provided, and surgical staging for vulvar cancer is explained. Options for treating vulvar carcinoma are presented, including the standard procedure of en bloc dissection of vulva and regional lymph nodes, the less mutilating separate groin incision approach, and radiotherapy. The current approach to managing vulvar cancer patients is discussed in terms of distinctive algorithms for decision making in situations involving early lateralized lesions; early centralized lesions; advanced disease caused by local extension; and advanced disease caused by clinically positive, enlarged, or fixed inguinal nodes. In addition, data on recurrences and survival rates are provided. 103 references, 4 figures, and 2 tables.
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Women and HIV/AIDS Source: HRSA Care Action December 1998; 1-12. Contact: US Department of Health and Human Services, Health Resources and Services Administration, HIV/AIDS Bureau, Office of Communications, 5600 Fishers Ln Rm 746, Rockville, MD, 20857, (301) 443-6652, http://www.hrsa.gov/hab. Summary: This newsletter discusses the clinical care of women with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). It provides statistics on HIV in women and factors that determine need in this population. These factors include parenthood, lack of awareness of risk and serostatus, discrimination, poverty, and psychological distress, violence, and substance abuse. Other topics include the delivery of quality care to HIV-positive women, conditions necessary for receiving care, and conditions for retaining women in care. The newsletter also discusses findings from studies on perinatal transmission of HIV and AZT, antiretroviral therapy and pregnancy, Cesarean section and vertical transmission, other risk factors for vertical transmission, gender and viral load, genital tract HIV, and the human papilloma virus and cervical dysplasia. It also provides four perspectives from female professionals (i.e., an executive director of a family planning council, a director of a county health department, and two researchers) involved in the delivery of services to women with HIV and information on a recommendation for routine HIV tests for pregnant women made by the Institute of Medicine (IOM) of the National Academy of Sciences.
Federally Funded Research on Human Papilloma Virus The U.S. Government supports a variety of research studies relating to human papilloma virus. These studies are tracked by the Office of Extramural Research at the National
Studies
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Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable 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 human papilloma virus. 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 human papilloma virus. The following is typical of the type of information found when searching the CRISP database for human papilloma virus: •
Project Title: A NOVEL DIAGNOSTIC FOR ONCOGENIC HPV Principal Investigator & Institution: Lu, Peter S.; Arbor Vita Corporation 772 Lucerne Dr Sunnyvale, Ca 940853844 Timing: Fiscal Year 2003; Project Start 22-JUL-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Arbor Vita proposes to detect and quantify oncogenic E6 proteins as a diagnostic test for Human Papilloma Virus (HPV) infection and cervical cancer. Oncogenic variants of HPVs have been correlated with cervical cancer at a frequency of 99.7%. Accumulated data unequivocally demonstrate that oncogenic E6 proteins are crucial for initiation and maintenance of cervical cell transformation and cancer progression, potentially representing a superior diagnostic marker. E6 proteins have not been successfully analyzed by standard methods. Research by Arbor Vita and others has shown that oncogenic E6 variants specifically bind to cellular PDZ domain proteins. Arbor Vita proposes to exploit this property as the basis of a simple test for the detection of oncogenic E6 variants. Specifically, Arbor Vita proposes to develop a PDZ domain-based oncogenic E6 detector that, as part of an ELISA-based test, selectively detects E6 oncoproteins: first, in vitro; secondly, in transfected cells; and thirdly, in HPV infected cancer cell lines. To accomplish these aims, Arbor Vita will utilize its proprietary in vitro assay. Tasks will include cloning, protein expression and purification, design of a ELISA based test system, and optimization of cell lysis conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALLOGENEIC STEM CELL TRANSPLANTS FOR HPV+CERVICAL CANCER Principal Investigator & Institution: Fefer, Alexander; Associate Professor; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 29-FEB-2004 Summary: (PROVIDED BY APPLICANT): Our long-range goal is to develop tumorspecific allogeneic adoptive T-cell immunotherapy in the context of non-myeloablative allogeneic hematopoietic stem cell transplantation (NST) for the treatment of nonhematologic malignancies. We have selected Human Papilloma Virus (HPV)-associated
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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cervical cancer as a model because it constitutively expresses HPV genes E6/E7, which are appropriate targets for immunotherapy, and because, when advanced, its prognosis with conventional therapies is dismal. However, in order to ultimately design a clinical trial of HPVE6/E7-specific allogeneic T-cell therapy, we first need to a) determine whether NST alone will exert a clinically detectable anti-tumor effect, and b) determine whether lymphocytes derived from donor stem cells and exposed to host tumor in vivo will acquire HPV E6/E7-specific reactivity detectable in vitro, and whether such reactivity can be augmented in vivo. Thus, as a first step, we propose to perform a Phase II clinical trial to a) study the anti-tumor efficacy, b) document the safety, c) monitor hematopoietic engraftment and lymphoid chimerism, and d) determine by concurrent immunologic monitoring whether T cells from the normal ste cell donors can acquire HPVE6/E7-specific reactivity in vivo or in vitro, with a view to eventual (after this grant period) ex vivo generation and expansion of HPVE6/E7-specific T cells for infusion. NST will consist of low-intensity, non-myeloablative but immunosuppressive conditioning, infusion of granulocyte-colony stimulating factor (G-CSF)-mobilized allogeneic peripheral blood stem cell (PBSC), post-transplant immnosuppression and, if there is progressive disease and/or mixed lymphoid chimerism after PBSC infusion, donor lymphocyte infusion (DLI). Accordingly, our specific aims are: 1. To perform a clinical trial of allogeneic NST in patients with advanced cervical carcinoma to: a. Determine the anti-tumor efficacy, b. Determine the safety, c. Monitor donor hematopoietic and lymphoid chimerism, 2. To perform laboratory immunologic monitoring studies to determine whether: a. Donor-derived cells obtained from recipients serially after NST have acquired HPV E6/E7-specific reactivity by exposure in vivo ("priming") to persisting tumor expressing these antigens, and b. Cells obtained directly from donors can acquire HPV E6/E7-specific reactivity after exposure in vitro to HPV E6/E7 synthetic peptides or recombinant proteins. The clinical and laboratory results are expected to provide a rational basis and direction for the design of subsequent trials of tumor-specific adoptive cellular immunotherapy in the context of this treatment regimen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POPULATION
ANTIOXIDANTS
NUTRIENTS
AMONG
A
BRAZILIAN
Principal Investigator & Institution: Giuliano, Anna R.; Associate Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 16-JUN-2000; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): Epidemiologic research conducted over the past couple of decades has shown that infection with the human papilloma virus (HPV) is a cause of most cases of cervical cancer. Prospective studies have shown that women infected with HPV are more likely to develop cervical intraepithelial neoplasia (CIN), and that those with persistent oncogenic type HPV infections are at a significantly increased risk of developing CIN compared with women transiently infected. In addition, persistently HPV positive women appear to be four times more likely to have persistent cervical lesions. Although HPV infection is a cause of cervical cancer, it may be an insufficient cause requiring the presence of other factors for the infection to progress to a significant cervical lesion. Nutritional status may be an important cofactor affecting both HPV persistence and progression of persistent HPV infection to CIN. However, the association between nutritional status and cervical carcinogenesis has not been adequately tested. The overall goal of this application is to determine, using prospectively collected HPV and cytology data, the association
Studies
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between serum carotenoid and tocopherol status and cervical carcinogenesis among a cohort of high risk study participants in the Brazilian HPV Natural History Cohort (RO1 CA70269). This project will provide the first prospective analysis of serum carotenoid and tocopherol concentrations and risk for persistent HPV infection; it will be based on sensitive and specific methods for assessing type of HPV infection over a 12 month period, and evaluate subsequent 5 year risk of progression to CIN. This proposed study is unique in that if focuses on early events in cervical carcinogenesis: HPV infection, HPV persistence, and progression to CIN. It is cost-effective, utilizing previously collected serum samples and questionnaire data. The study utilizes state of the art methods for determining both PV status and serum carotenoid and tocopherol status. Furthermore, it incorporates multiple measurements of both HPV status and serum nutrient concentrations minimizing the probability that measurement imprecision resulting from temporal fluctuations will obscure the true association between nutrients status, and HPV persistence and risk of CIN. Results from this study will efficiently further our understanding of the role of antioxidant nutrients and cervical carcinogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOMARKER/HEALTH BEHAVIOR/COMORBIDITIY IN CANCER RECURRENCE Principal Investigator & Institution: Duffy, Sonia; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): A variety of past studies have provided insightful, but varied information about the predictors of tumor recurrence, survival, and quality life in patients with head and neck cancer, however, none of the studies have prospectively assessed the nature, relative strength, and interrelationships of these factors together as predictors of recurrence, survival, and quality of life. The specific aims of this study are to test the hypotheses that: 1) health behaviors (smoking and alcohol use), comorbidities, and molecular markers (tumor p53, serum human papilloma virus (HPV-16), and serum vascular endothelial growth factor (VEGF)) are predictors of tumor recurrence; 2)health behaviors, comorbidities, and molecular markers are predictors of survival; 3) health behaviors and comorbidities are predictors of quality of life; and, 4) serum HPV-16 and serum VEGF are sensitive and specific tests for the identification of tumors with high levels of tumor HPV- 16 and tumor VEGF. This observational, longitudinal study will be conducted at three hospitals and enroll 1391 patients. Information on health behaviors, clinical characteristics, treatment modalities, and demographics will be collected through patient surveys and hospital records. Serum will be collected every 3 months for assessment of levels of HPV-16 and VEGF. Tumor tissue will be collected at time of initial tumor biopsy or tumor resection and analyzed for p53, HPV-16, VEGF and for construction of tissue microarrays as a SPORE resource for future molecular epidemiologic studies. Independent variables of interest will include health behaviors, comorbidities, and molecular markers while controlling for tumor site and stage, treatment modalities, and demographic factors. Dependent variables will include 1) tumor recurrence, 2) survival, and 3) quality of life. Stratified and multivariate analyses for cross-sectional and cohort data (e.g. survival data) will then be performed (e.g. Cox proportional hazard models). Newly developed advanced statistical techniques will be used to jointly model the longitudinal biomarkers and survival and tumor recurrence. Advanced techniques for longitudinal data will be used to analyze the quality of life data. The sensitivity and specificity of serum HPV-16 and VEGF will also be calculated in a cohort of patients by correlating each serum
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marker to its respective tumor marker. The results of this study are expected to directly translate into improvements in detecting tumor recurrence, improving survival, and increasing quality of life for head and neck cancer patients and will provide useful information about screening and prevention services needed by this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER IMMUNOTHERAPEUTICS PROGRAM Principal Investigator & Institution: Raubitschek, Andrew A.; Director; Beckman Research Inst of City of Hope Helford Building Duarte, Ca 910103000 Timing: Fiscal Year 2003; Project Start 07-FEB-2003; Project End 30-NOV-2007 Summary: The overall scientific goal of the Cancer Immunotherapeutics Program (CIP) is to develop immunologic based therapeutics for the treatment of both hematologic malignancies and solid tumors. The program is an outgrowth of two major research efforts at COH, Radioimmunotherapy and Hematopoietic Transplantation for Hematologic Malignancies. The focus of the program is to utilize the advances in molecular immunology to combat a variety of malignancies. The Program has three major subdivisions: Radioimmunotherapy (RIT), Cellular Immunotherapy(CIT), and Molecular Immunotherapeutics(MIT). The specific aims are: (a) to develop genetically engineered antibody constructs as diagnostic imaging agents directed against CEA, Her2, and PSCA (prostate stem cell antigen); (b) to apply genetically engineered radiolabeled antibody constructs for the treatment of patients with solid malignancies; (c) to develop radiolabeled anti-lymphoma/leukemia antibodies as conditioning reagents for stem cell transplantation; (d) to explore adoptive T-cell therapy for targeting minimal residual disease following stem cell transplantation, targeting metastatic solid tumors, and targeting primary brain tumors; (e) to develop immunofusions between antibodies and lymphokines as cancer therapeutics used alone or with RIT or CIT); (f) to develop dendritic cell immunotherapy based on AAV carrying target peptide epitopes for CML and human papilloma virus. The elements of this program are highly interactive with each other and highly interactive with other programs within the Cancer Center. The Clinical and Experimental Therapeutics Program collaborates on the RIT trials combining chemotherapy. The Hematologic Malignancies Program collaborates on the clinical aspects of the RIT/stem cell transplantation protocols as well as the clinical aspects of the adoptive T-cell protocols for patients with hematologic malignancies. In addition, the program has collaborated extensively outside COH with UCLA, MSKCC, and FHCRC. The Program is led by Dr. Andrew Raubitschek and Dr. Michael Jensen. Their combined experience in the molecular engineering of antibodies, the molecular engineering of T cells, the production and purification of clinical grade antibodies and cellular therapeutics, and their ability to radiolabel the products to evaluate localization in patients and animals provide the required infrastructure to build an effective translational research program in Cancer Immunotherapeutics. This clinical effort is significantly aided by the recently completed Center for BioMedicine and Genetics, and Drs. Couture and DiGiusto, who direct the facility. The members of the program have initiated several novel therapeutics into the clinic and in the process have filed nearly a dozen INDs with the FDA for carry out their trials. The 11 Full and 10 Associate Members of the program have published 97 articles, books, book chapters, etc., since the last competitive grant review. Of these, 51 are intraprogrammatic publications, 12 are interprogrammatic publications, and 11 are both. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER IMMUNOTHERAPY FOR HEAD AND NECK TUMORS Principal Investigator & Institution: Sewell, Duane A.; Otorhinolaryngology Head & Neck Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): It is my long-term career goal to become a clinicianscientist in the field of head and neck cancer. Despite medical advances in other areas, treatment modalities for head and neck cancer have not changed over the past 30 years. Surgery, radiation, and chemotherapy are still the mainstays of treatment, and five-year survival rates for many tumors remain poor. New therapies are needed. Recent studies indicate that most oropharyngeal squamous cell carcinomas have undergone transformation by human papilloma virus (HPV). Two early transforming HPV proteins, E6 and E7, are expressed in these tumors and they provide attractive targets for cancer immunotherapy. Listeria monocytogenes-based vaccines have been developed that cause regression of HPV-associated tumors in animal models. In this proposal, we hope to develop new strategies that will make this type of therapy more effective and clinically applicable. In Specific Aim #1, we will test a unique strategy that targets both transforming proteins expressed in HPV-associated tumors. Heretofore, experiments and clinical trials have only targeted either E6 or E7. Several different live recombinant vaccines, including Listeria and Vaccinia constructs, will be used in order to determine which combination is the most efficacious. In Specific Aim #2, a novel Listeria construct will be engineered. This construct will include the Listeria protein ActA fused to the transforming proteins. The rationale behind creating this vaccine is the fact that ActA contains several PEST (P, proline; E, glutamic acid; S, serine; T, threonine) regions within its amino acid sequence. PEST regions have recently been shown to be critical for the efficacy of the Listeria constructs. In Specific Aim #3, we will develop transgenic mice that will express E6 and E7 under the control of the thyroglobulin promoter. These mice will spontaneously produce HPV-transformed thyroid tumors. Using this model, the vaccines targeting HPV-associated tumors will be tested in mice with head and neck tumors that may be tolerant to the transforming proteins. This model mimics the situation that is seen in human head and neck cancer patients. In order to achieve my goal of treating these patients with immunotherapy, I am applying for a period of mentored research in Dr. Yvonne Paterson's laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER IMMUNOTHERAPY WITH A LIVE RECOMBINANT VACCINE Principal Investigator & Institution: Paterson, Yvonne; Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 30-JUN-2005 Summary: (provided by applicant): During the last funding period, we developed two Listeria monocytogenes based vaccines, Lm-E7 and LmLLO-E7, that induce immunity to the Human Papilloma Virus (HPV) oncogenic protein E7 but only Lm-LLO-E7 causes the regression of HPV immortalized tumors established in the mouse. We have discovered differences in the anti-E7 immunity induced by these vaccines that may explain their different efficacies in killing E7 expressing tumors. We request funding to explore these findings in an HPV-E7 system consisting of mouse tumors, naturally immortalized by HPV, transplanted into either syngeneic wild type mice or syngeneic mice transgenic for the E7 gene. We hypothesize that the efficacy of E7 based immunogens in inducing the regression of established cancer is related to the type of
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CD8+ and CD4+ T cell immunity induced. We have shown that both vaccines induce similar levels of CTL activity against E7 expressing tumor cells and high numbers of CD8+ T cells that stain with peptide/MHC class I tetramers. However, the cytokine profile of the CD8+ T cells, as determined by intra-cellular cytokine staining, is quite distinct. We have also shown that whereas CD4+ T cells induced by Lm-LLO-E7 are required for anti-tumor efficacy, this subset is counter productive to the ability of Lm-E7 to cure mice of E7 expressing tumors. In our first specific aim we will characterize the T cell responses induced by Lm-E7 and Lm-LLO-E7 in the spleen and those that home to the tumor. We also hypothesize that E7 is more immunogenic and will induce better anti-tumor immunity if it is delivered as a fusion protein with a listerial protein (LLO). We have already shown that both vaccinia virus and L. monocytogenes that expresses LLO-E7 are much more potent tumor immunotherapeutics than when they carry E7 alone. In our second specific aim we wish to determine whether LLO-E7 protein delivered by conventional adjuvants or pulsed dendritic cells can produce better antitumor immunotherapy than E7 alone. If the immunogenicity of a tumor associated antigen can be enhanced by fusion to this bacterial protein then we may be able to develop immunotherapeutic strategies that are safer than those that use live recombinant vectors to deliver the antigen. Finally, an important requirement for establishing the efficacy of any cancer therapeutic in mice is to show that it can induce immunity against endogenous antigens which may have induced immune tolerance in the host. In our third specific aim, we will test the most promising vaccine delivery systems in a transgenic mouse model for E7. The findings of these studies may be generally applicable to other cancer approaches and to the measurement of immune components that are indicative of good tumor immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER VACCINES TO HPV-16 ASSOCIATED TUMOR Principal Investigator & Institution: Ertl, Hildegund Cj.; Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-JAN-2003 Summary: (Applicant's Abstract) Vaccination is the most effective medical intervention to reduce human morbidity and mortality due to infectious diseases. The development of efficacious vaccines for treatment or prevention of cancer has been less successful, which is in part due to a lack of well-defined tumor-specific antigens. Most cervical cancers, the second most common cause of malignancies in women worldwide, are associated with genital infections by human papilloma viruses (HPV) strains, 16 or 18 that express two oncoproteins, i.e., E6 and E7 which might provide highly suitable target antigens for immunological intervention. The aim of this application is to test three different vaccine prototypes, i.e., DNA vaccines, vaccinia virus recombinants and E1-deleted replication defective adenovirus recombinants expressing the E6 or E7 protein of human papilloma virus (HPV)-16, in a mouse model for their efficacy in limiting the spread of E6 and E7 expressing tumors. The applicant's long-term goal is to develop a vaccine for treatment of women with HPV-16 associated cervical cancer. She has developed a mouse tumor model to study vaccines to E6 and E7 of HPV-16. The applicant also generated a number of vaccines, i.e., DNA vaccines, recombinant vaccinia and E1-deleted adenoviral vaccines, expressing the oncoproteins of HPV-16. All of these types of expression systems, that have distinctive advantages and disadvantages as vaccine carriers, were shown to induce partial protection against a low dose tumor challenge. The applicant's hypothesis is that a combination of different types of vaccines given as prime-boost regimens either alone or with a cytokine adjuvant might
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significantly improve the efficacy of vaccination in providing long-term protective immunity against HPV-16 E6 and E7 transformed tumors. To test this hypothesis she will initially compare the three different types of vaccines given individually analyzing basic parameters such as the kinetics of the response, dose-response curves, different routes of immunization, effect of pre-existing immunity to the vaccine carrier, and induction of different types of immune responses. The applicant will then test the effect of different vaccine combinations including interleukin(IL)-12 as an adjuvant on solid and metastatic tumors both in a prophylactic immunization model as well as in treatment of already established tumors. In case the applicant's hypothesis is correct, data gathered within the realm of this application will serve as the basis for a clinical Phase I trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF NEW HUMAN P53 DISSOCIATORS Principal Investigator & Institution: Brachmann, Rainer K.; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The human tumor suppressor protein and transcription factor p53 integrates stress signals, such as DNA damage, hypoxia and ribonucleotide depletion, and induces either cell cycle arrest or apoptosis. Approximately 50 percent of all human cancers carry p53 gene mutations. Another 5 to 10 percent inactivate the p53 protein directly by overexpression of high-risk human papilloma virus (HPV) E6 or MDM2, a physiological negative regulator of p53. Considering the plethora of upstream signals, all using different mechanisms of p53 activation, and of p53 downstream effector genes, it is very likely that the remaining human cancers also directly inactivate p53 protein by overexpressing currently unknown negative regulators of p53. We devised a genetic assay for p53 in S. cerevisiae, called the "p53 dissociator assay", to select for such, and other, proteins important for p53 biology in highly efficient screens. We showed that SV40 large T antigen, a known negative regulator, scores in this assay, and we recreated the complex interplay of p53, E6-associated protein (E6-AP) and high-risk HPV E6 resulting in p53 degradation. Three p53 dissociator screens yielded MDM2 and high-risk HPV E6, two established negative regulators, 53BP1, a coactivator of p53, and 23 candidate proteins without current connections to p53 biology. Besides negative and positive regulators of p53, we may also have isolated proteins negatively regulated by p53 in human cells, as suggested by their biology. All three classes of proteins represent important drug targets for improved cancer therapies: inhibition of negative regulators will unleash p53 and induce apoptosis in cancer cells, studies of p53 enhancers will elucidate new mechanisms of further potentiating p53 activity and proteins negatively regulated by p53 will provide new directions to interfere pharmacologically with unchecked proliferation. We propose to study the set of candidate proteins using secondary yeast and mammalian assays, followed by assays tailored to the classes that confirmed p53 dissociators likely belong to. Novel negative regulators of p53 will be pursued further by checking for their overexpression in cancer cell lines with wild-type p53 genes and by setting up reverse two-hybrid assays to screen for drugs able to abrogate their effect on p53. Several specific ways of direct p53 protein inactivation exist, but their exact mechanisms have not been elucidated: cytoplasmic sequestration, p53 degradation involving the human protein E6-AP and nuclear sequestration in teratocarcinoma cell lines. To identify the proteins underlying these mechanisms, we will perform additional targeted D53 dissociator screens in the presence of E6-A P and using specific cDNA libraries.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COSTIMULATION IN DEFENSE AGAINST VIRALLY INDUCED TUMORS Principal Investigator & Institution: Larsen, Christian P.; Professor of Surgery Transplant Center; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: This proposal focuses on the elucidation of the role of co-stimulation in the defense against virally induced neoplasma. Virally-induced neoplasms are a major cause of morbidity and mortality in humans that are chronically immunosupressed, as in transplant recipients, patients treated for autoimmune disorders, and the acquired immune deficiency syndrome (AIDS). Virally induced tumors include Kaposi's sarcoma, caused by HHV8, non-Hodgkins lymphoma, caused by Epstein-Barr virus, and cutaneous and cervical carcinoma caused by human papilloma virus. In order for these acquired viruses to cause cancer in humans, the immune system must tolerate viral antigens. We have developed a murine model of a virally-induced endothelial tumor, analogous to Kaposi's sarcoma. This tumor, SVR, was derived by the sequential introduction of SVRO large T antigen and oncogenic H-ras into murine microvascular endothelial cells, and is highly tumorigenic in nude mice, but is rejected by syngeneic C57BL6 mice. We wish to determine the role the costimulatory dependent and independent pathways involved in the rejection of a virally induced endothelial tumor. This knowledge may allow therapeutic immune suppression without the potentially lethal consequences of virally-induced neoplasia. In addition, this model could be useful for evaluating novel immunosuppressive therapies, since the endothelium is the first target for immune rejection in solid organs. Specific Aims: 1) We will determine the role of CD4 and CD8 T lymphocyte subsets in the rejection of SVR tumors in syngeneic mice. 2) We will determine the role of the co-stimulatory molecules CD28, CD40, and CD40 ligand (CD40L) in the rejection of SVR tumors. 3) We will determine whether the presence of lymphoid tissue and spleen is required for rejection of SVR cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRYOEM AND IMAGE RECONSTRUCTION OF VIRUSES Principal Investigator & Institution: Baker, Timothy S.; Professor; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2001 Summary: Viruses are parasites of their hosts. Hence, the life cycle of any virus is inextricably tied to that of the host cell. Despite this dependence, all viruses share a number of essential tasks which they must accomplish for survival. A virus must be able to find and recognize a cell in which it can replicate, release its genome into the cell, generate new viral components by transcription and translation and assembly these components into precursors that mature into a stable progeny virion which is released from the host cell and transmitted to encounter a new host. Different viruses accomplish these tasks in different ways as a result of adaptation to different cellular environments. Each of these tasks involves interactions between components within the context of the whole virion and hence require the visualization of the entire structure at which the techniques of cryo-transmission electron microscopy (cryoTEM) and three-dimensional (3D) image reconstruction ('cryo-reconstruction') excel. We have exploited cryoreconstruction techniques to study a diverse range of viruses, including those that infect mammals as well as insects, bacteria, and plants (including fungi and algae). Several
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studies funded by the current PPG have illustrated the structural response of different viruses to the common tasks of the viral life cycle. This proposal involves several new cryo-reconstruction studies aimed at exploring the structural basis for key aspects of viral infection. Work with the Kuhn and Rossmann laboratories will continue analyses of the assembly of several enveloped viruses of the alphavirus gene (Togavirus family). We will also initiate new studies of the assembly of three important human pathogenesis: rubella virus (rubrivirus genus) and two members of the closely related Flavivirus family of enveloped viruses, yellow fever virus and Hepatitis C virus. A collaboration with Smith's laboratory will address issues related to viral transmission in two plant viruses, cucumber mosaic virus and zucchini yellow mosaic virus. A collaboration with Friedman's laboratory will define viral epitopes on human papilloma viruses, including the carcinogenic, HPV serotype 16. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CRYSTALLOGRAPHY OF HETEROTRIMERIC COMPLEXES W/ REGULATORS & EFFECTORS
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Principal Investigator & Institution: Sprang, Stephen R.; Professor; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001 Summary: Data collected at MacCHESS under express mode proposal EM188 were used in the structure determination of the DPC4 and retinoblastoma (Rb) tumor suppressor proteins. DPC4 (now also known as Smad4) signals from TGFb superfamily receptor Ser/Thr protein kinases at the cell surface to the nucleus through homo- and heterooligomeric interactions. The crystal structure of the C-terminal domain (CTD) of DPC4, determined at 2.0 resolution, revelas that the DPC4-CTD forms a crystallographic trimer through a conserved protein-protein interface to which the majority of the tumorderived missense mutations map. We showed that these mutations disrupt homooligomerization in vitro and in vivo, and suggested the hypothesis that the trimeric assembly of the Smad4/DPC4-CTD is a critical function in signaling that is targeted by tumorigenic mutations. Because our paper describing the DPC4 structure (1) went in press while we were collecting data at MacCHESS, it only describes a 2.5 -refined structure. The coordinates submitted to the Brookhaven Protein Data Bank were refined using the 2.0 data collected at MacCHESS. The retinoblastoma tumor suppressor, which in most human cancers is inactivated by mutations, is instead inactivated by the human papilloma virus E7 oncoprotein in cervical cancer. The crystal structure of Rb bound to a nine residue E7 peptide containing the LxCxE motif, shared by other Rbbidning viral and cellular proteins, was determined at 1.85 resolution (2). The structure shows that the LxCxE peptide binds a highly conserved groove on the B box or the interface with the A box, which the structure shows is required for the stable folding of the B box. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYCLIN E EXPRESSION IN HUMAN CANCER Principal Investigator & Institution: Porter, Peggy L.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: The study of "Cyclin E Expression in Human Breast Cancer" seeks to extend our studies of the role of cyclin E and the cell cycle inhibitor p27kip1 in human cancer for 3 additional years. Over the past grant period, we evaluated archival breast tissue
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samples from 913 young women diagnosed with invasive breast cancer and from 225 women diagnosed with ductal carcinoma in situ (DCIS) for expression of cyclin E and the cell cycle inhibitor p27 in the context of other tumor characteristics, clinical presentation and clinical outcome. In the continuation of this project, we propose a) determine the association of p27 and cyclin with survival at 7 and 10 years as these data become available, and incorporate analyses of the modifying effect of specific therapeutic regimens on survival with respect to cell cycle abnormalities, and b) complete the analysis of the data from women with DCIS to determine the association of cell cycle regulatory proteins and recurrence of disease. We also propose to expand the study to include evaluation of cyclin E and p27 and potential mediators of p27 and/or cyclin E (c-myc, an oncogene that appears to cooperate with p27 in tumorigenesis; cullin-3, a newly identified gene product that targets cyclin E for degradation; and centrosome abnormalities detected by pericentrin immunohistochemistry) in 2 additional groups of women: 1) breast tumors from 576 women unselected for age at diagnosis and 2) tumors from 173 women with HPV-related adenocarcinoma of the cervix. These new study populations will allow us to examine the association between p27 and cyclin E and breast cancer survival in a group of women unselected for age, and in a second tumor type that may exhibit different patterns of cell cycle expression due to the involvement by human papilloma virus (HPV). Considerable evidence is developing that indicates abnormalities of cyclin E and p27 are associated with the initiation and progression of human cancer. It is not known if loss of p27 expression or overexpression of cyclin E are causal, or what role regulators of their expression and degradation play in tumorigenesis. We are developing profiles of cycle regulatory proteins that have the potential to stratify patients into prognostically relevant categories As the genes and the protein products that cooperate with, or regulate the known cell cycle regulatory proteins, are identified and evaluated in sufficient numbers of tumor samples, we will be better able to inform the development of targeted treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOTOXIC T LYMPHOCYTE RESPONSE TO HPV 16 Principal Investigator & Institution: Nakagawa, Mayumi; Laboratory Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: (Applicant's Description) As a student in an M.D.-Ph.D. program at Albert Einstein College of Medicine, Dr. Nakagawa studied the structure function relationships of murine Major Histocompatibility Complex in terms of its immunological and physiological properties. After completing a residency program in laboratory medicine at the University of California at San Francisco, where she still is, she began a research project studying cell-mediated immunity to Human Papilloma Virus type 16 (HPV 16) which is a causative agent of cervical dysplasia and cancer. Data collected thus far, using a T cell proliferative assay as well as a cytotoxic lymphocyte assay, support her working hypothesis that cell-mediated immunity to HPV is instrumental in its elimination and thus is protected against the development of associated diseases. The experiments proposed in this application are nested with an ongoing longitudinal study in which HPV 16 infected women who have not developed high grade intraepithelial lesions are tested for cytotoxic T lymphocyte responses to HPV 16 oncogenic proteins, E6 and E7. The specific aims of this project are to characterize the lymphocyte subset(s) responsible for anti-HPV activity, to eliminate background activity, to explore alternative methods of in vitro stimulation, and to develop a protocol to perform cytotoxic T lymphocyte
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assay using T cell lines instead of bulk cultures. The last aim will give us a tool to identify immunodominant epitopes of HPV 16 in the future. The long-term goal of this project is to develop effective vaccines and immunotherapy for prevention and treatment of cervical cancer. Dr. Nakagawa's long-term career goal is to continue research in HPV immunology as an independent investigator. She envisions this will be best accomplished by becoming a faculty member at an academic medical center where she will also have clinical responsibilities as a laboratory medicine physician. The University of California at San Francisco, which is a major academic medical institution with many distinguished scientists, offers an excellent environment to develop skills and further her expertise in the field to accomplish her goals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCED SINGLE-VISIT CERVICAL CANCER SCREENING PROGRAM Principal Investigator & Institution: Manetta, Alberto; Professor; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 01-SEP-1998; Project End 30-JUN-2008 Summary: (provided by investigator): An innovative approach to screen women for cervix cancer and provide early treatment for severe cervix dysplasia in a single-visit program (SVP) is ongoing in a Latino/Hispanic community as part of the current Single-Visit Cervical Cancer Prevention Program application (7/1/98-6/30/03). This continuation application is designed to further increase the effectiveness of the singlevisit program (SVP). The first aim is to implement and evaluate a process to identify women in local Latino/Hispanic communities who have oncogenic type human Papilloma virus (HPV) infections, known precursors for cervix dysplasia and cervical cancer, and recruit them for the SVP. Health disparities exist in the incidence of cervical cancer among racial/ethnic groups with Hispanic women (Latinas) among the groups experiencing higher rates. Screening procedures to identify Latinas with oncogenic type HPV infections may contribute to identification of women at most risk for cervix cancer. HPV self-sampling in the home, as proposed in this study, has not been tested. The process will involve the distribution of HPV Home Self-administered Sample Collection (HSASC) kits to 4000 Latinas. Recruitment will continue until a minimum of 1840 selfsamples has been returned, of which 9.14% (N=168) are expected to be HPV-positive. Latinas with HPV-positive self-samples will be invited to come to one of two clinics offering the SVP. A 60% response rate (N=135) is expected. Additionally, twice as many women with HPV-negative samples matched by age and recruitment method will be invited to participate (N=270). Sensitivity and specificity analysis will be done using samples obtained by a provider during the subsequent clinic visit as the reference. Satisfaction with self-sampling compared to provider sampling will be evaluated. An increase of approximately 60% is estimated in the proportion of women with severe cervix dysplasia who enter the SVP. The second aim is to evaluate the impact of Promotoras on the recruitment of Latinas in the clinical trial. Two recruitment and HSASC kit distribution methods will be used: media-based ad campaign with mail distribution and Promotora distribution. Promotoras will recruit 3,200 Latinas to receive HSASC kits with an estimated self-sample return rate of 50% (1,600 self-samples). The media-based ad campaign will be used to recruit another 800 Latinas who will receive the HSASC kit in the mail. A 30% (N=240) self-sample return rate is expected. Comparisons of return rates and satisfaction with recruitment and distribution method will be tested. The third aim is to evaluate the cost-effectiveness of the HSASC program and HPV testing as an adjunct to the SVP program. Cost-effectiveness analysis will be
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used to measure the ratio of program dollar net costs or cost savings to program effectiveness, which are the non-dollar net program outcomes. The incremental net cost associated with an incremental improvement in outcomes in terms of quality-adjusted life years (QALYs) will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPITOPE DRIVEN HPV VACCINE TARGETING DENTRITIC CELLS Principal Investigator & Institution: Martin, William D.; Chief Information Officer; Epivax, Inc. 365 Hope St Providence, Ri 02906 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: Human Papilloma Virus (HPV) types 16 and 18 are detected in roughly 70% of all invasive cervical tumors. Among cytologically normal women, detection of HPV infection by PCR has been shown to increase the subsequent risk of cervical cytologic abnormalities by 12 fold, suggesting that effective vaccines (preventive/therapeutic) for HPV infection would be a useful medical advance in the battle against this cancer. EpiVax is developing a dendritic cell-directed DNA vaccine against HPV 16, 18, and other cervical cancer-associated HPV types. For this project, we have selected 100 novel HPV peptides that represent putative MHC class I and class II restricted T cell epitopes, primarily derived from the E1, E2, E6, E7 and L1 proteins of selected HPV types. Binding studies and CTL studies will be performed to select the best candidates for vaccine development Selected epitopes will be inserted in a DNA vector. Additional DNA vaccine development, safety, toxicity, and protection studies will be carried out in Phase II. The specific aims of this project are to: * Screen putative HPV epitopes for MHC binding and HPV-specific T cell recognition * Construct DNA vaccine vectors containing candidate HPV epitopes * Evaluate DNA vector expression in human dendritic cells in vitro. PROPOSED COMMERCIAL APPLICATIONS: A therapeutic anti-HPV vaccine would have a tremendous market impact since existing cervical screening programs cost nearly $6 billion annually in the United States. Also, most sexually active women have been exposed to HPV, so it is unlikely that a prophylactic HPV vaccine will confer protection. A novel immunologic therapy to treat existing HPV infection as well as HPV-associated cervical cancer, such as the one we propose, may represent an attractive and cost effective treatment alternative. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXPERIMENTAL TRANSFORMATION OF HUMAN MELANOCYTES IN VIVO Principal Investigator & Institution: Herlyn, Meenhard; Professor and Chairman; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-JAN-2004 Summary: Experimental animal models for human melanoma development have been difficult to establish because of the unique architectural and functional characteristics of human skin hampering investigations on etiology, diagnosis, and prevention of the disease. Epidemiological observations suggest a role for ultraviolet (UV) light irradiation in the etiology of human melanoma but direct evidence is still missing. The histological diagnosis of precursor dysplastic nevi and biologically early primary melanomas continuous to be difficult and controversial, even among experts, and there is currently little understanding of gene aberrations and their importance for melanoma development. To better understand development of human melanoma and to detect melanocytic lesions at the earliest stages with new molecular markers, we have
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developed a human skin graft model in immunodeficient RAG-1 mice in which human skill from newborns is exposed to the chemical carcinogen 7,12dimethyl(a)benzanthracene (DMBA) followed by UV irradiation for up to 10 months. Preliminary studies with this model have revealed melanocytic hyperplasia, lentigo, dysplasia, and melanoma. Using a refined grafting technique we are now able to graft skin from adults and will select donors who have a high susceptibility for developing dysplastic nevi and/or melanomas to determine the optimal UV wavelength for induction of melanocytic lesions and to develop new criteria for melanocyte transformation in vivo, including proliferation, escape of melanocytes from control by keratinocytes, loss of melanocyte contact from basement membrane and morphological changes associated with melanocytic dysplasia. We will then define new molecular markers for transformation using microarrays for analyses of mRNA expression in cells from microdissected lesions or short-term cultures. These initial screening approaches are followed by immunohistochemistry and in situ hybridization analyses to provided information on gene expression in single cells at the RNA and protein levels, respectively. To investigate the role of major check point genes, we will transduce melanocytes in vitro with either the E6 gene or human papilloma virus for p53 sequestration or with H-ra for ras activation. Transduced melanocytes will then be included into skin reconstructs consisting of dermis and epidermis prior to grafting in vivo and long-term UV irradiation. Our unique in vitro/in vivo models are suitable to investigate etiology, early detection, and prevention of human melanoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FLOW CYTOMETRY STUDY OF T CELL RESPONSES TO HIV VACCINES Principal Investigator & Institution: Mccune, Joseph M.; Senior Investigator, Professor and Assoc; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2003 Summary: The evaluation of HIV-1 vaccines will be facilitated by the availability of better assays for HIV-1-specific human CD4+ and CD8+ T cell immunity. Such assays should be robust, reproducible, and amenable to high throughput analysis of transshipped clinical specimens. We have developed and optimized a flow cytometry-based assay to detect specific CD4+ and CD8+ human T cell responses to cytomegalovirus (CMV) in cohorts of HIV-1-infected patients. This "cytokine flow cytometry" (CFC) assay has shown that the presence of CD4+ T cell responses against CMV is correlated with the absence or resolution of CMV-associated end organ disease. More recently, results from this assay have been shown to correlate with results obtained using major histocompatibility complex (MHC) Class I tetramers bearing specific epitopes of CMV. Since the CFC assay appears to reliably and specifically detect such antigen-specific responses, we have also developed related assays capable of detecting specific human CD4+ and CD8+ T cell responses to other AIDS-related opportunistic infections, including those caused by Mycobacterium tuberculosis, the Mycobacterium avium complex, cryptococcus, and human papilloma virus. We now propose to devise a similar CFC assay for the detection and quantitation of CD4+ and CD8+ human T cell responses against epitopes of HIV-1. Preliminary experiments indicate that it is possible to detect such responses against a whole virus vaccine preparation and against defined epitopes of HIV-1 Gag. To develop, optimize, and standardize this CFC assay, and to correlate it with results obtained using MHC Class I/HIV-1 peptide tetramers (Specific Aim 1), we have formed a collaboration with Becton Dickinson Biosciences, a leading flow cytometry reagent and equipment manufacturer and distributor. To further
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evaluate this CFC assay, we have made plans to analyze HIV-1-specific immune responses in patients who have been exposed to but not infected by HIV-1, who are in varying stages of HIV-1 disease progression, or who are HIV-1-infected nonprogressors (Specific Aim 2). Finally, to determine whether the results from this assay may facilitate the design and development of HIV-1 vaccines, we have established collaborations with several research groups that are testing HIV-1 vaccines (including The Immune Response Corporation, Chiron, VaxGen, and the laboratory of Dr. David Weiner at University of Pennsylvania) and we have made plans to analyze HIV-1-specific T cell responses in both HIV- 1-seropositive and -seronegative vaccinees (Specific Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HPV IN DIFFERENTIATED HUMAN AIRWAY EPITHELIA IN VITRO Principal Investigator & Institution: Lee, John H.; Otolaryngology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The goal of this application is to develop Dr. John Lee into an independent physician/scientist. Drs. Welsh and Klingelhutz will assume responsibility as mentors to ensure success in his development. The heart of this proposal is intensive laboratory training in the pathogenesis of human papilloma virus (HPV) related airway disease. HPV infection of the aerodigestive tract results in papilloma formation and the development of squamous cell cancer, leading causes of dysphonia and aphonia. An understanding of disease pathogenesis has been limited by the lack of an in vitro model of differentiated human airway epithelia (HAE) and the inability to produce experimentally useful quantities of HPV virions. However, our lab now routinely produces in vitro models of well-differentiated HAE. Moreover, studies in keratinocytes have circumvented the lack of HPV virions by delivering the HPV genome by transfection. However, airway epithelia have marked differences from keratinocytes, and comparable transfection methods cannot be used in airway epithelia. Therefore, I developed a novel strategy to deliver an HPV genome inserted in a recombinant adenovirus. In preliminary studies, I demonstrated the feasibility of this approach by transferring the HPV genome with high efficiency to well-differentiated HAE. The HPV genome was excised from the vector and circularized. These results allow me to now ask the following questions about the interaction between HPV and HAE. 1) What factors influence the establishment of viral persistence in human airway epithelia? I will learn whether the HPV genome persists in HAE, and whether it exists as an episome or as integrated DNA. The data will also show us how epithelial differentiation influences the pattern of genome persistence. 2) Does the HPV genome alter the morphology or differentiation of human airway epithelia? Studies addressing this question will help us understand cellular changes associated with HPV-induced alterations of the epithelium in vivo. 3) Do human airway epithelia produce infectious HPV virions? The answer to this question will provide important insight into the factors involved in a productive viral infection. 4) What is the temporal and spatial pattern of HPV gene expression in differentiated human airway epithelia? An investigation of the timing, localization, and quantity of viral mRNA and protein expression will begin to show us how differentiation impacts the viral life cycle. These studies will provide new insight into HPV-related airway disease and should hasten the development of new treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN MAMMARY EPITHELIAL CELL IMMORTALIZATION Principal Investigator & Institution: Band, Vimla; Professor of Medicine and Director; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2001; Project Start 12-DEC-1997; Project End 30-NOV-2002 Summary: (adapted from the investigator's abstract) Mutations of the p53 tumor suppressor gene are the most frequent genetic lesion in breast cancer, suggesting a critical role for normal p53 protein in regulating mammary cell growth. The p53 mutations observed in various cancers have been shown to alter the biochemical functions of the p53 protein; however, it is not known which p53 functions are critical for its role in breast oncogenesis. Using the E6 oncogene of the human papilloma virus 16 (HPV16), they demonstrated that the loss of p53 protein was essential for immortalization of mammary epithelial cells (MECs). Recently, they have identified three p53 mutants, del239, R175H and R249S, which themselves are capable of inducing MEC immortalization, providing a unique system to delineate the p53 functions that are critical for MEC immortalization. Here, they propose analyses to elucidate the biochemical basis of mutant p53-induced MEC immortalization. Toward this goal we will (i) delineate the structural requirements for mutant p53-induced MEC immortalization by assessing the immortalizing ability of specific p53 mutants that alter its binding and transcriptional activation domains, (ii) analyze the effects of p53 mutants on p53-mediated transcriptional activation, repression, G1 arrest, and apoptosis. (iii) examine the in vivo association of p53 mutants with known cellular binding proteins. In particular, they propose to determine the primary structure of a del239 mutant-specific cellular binding protein p50 and to ascertain its role in mutant p53-induced immortalization. These studies, designed to identify the specific p53 functions that are targeted by immortalizing p53 mutants, should lead to a better understanding of how wild-type p53 controls normal MEC growth and how p53 mutations may contribute to the evolution of human breast cancer. Identification of novel targets of p53 function and oncogenesis in breast cells should be an important first step toward design of novel molecular therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE SUPPRESSION AND IMMUNE ESCAPE IN TUMOR MODELS Principal Investigator & Institution: Kast, W Martin.; Professor; Ob, Gyn, and Reproductive Med; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 05-AUG-1998; Project End 31-MAY-2003 Summary: (Adapted from the Investigator's Abstract): In recent years the investigators have studied the immune responses and developed vaccines against virus-induced tumors. Especially human papilloma virus type 16 related to cervical cancer has been the focus of their attention. In order to design a peptide based therapeutic vaccine for human use, they have developed two important mouse tumor models namely human papilloma virus type 16 plus activated ras induced tumors and human adenovirus plus activated ras induced tumors. Despite successes in prevention of tumor outgrowth through vaccination in these tumor models, only very limited success was obtained in therapeutic use of these vaccines. Several hurdles like immune suppression and immune escape in these tumor models stood or could stand in the way of therapeutic results. These potential hurdles are: 1) Activated ras induced immune suppression and immune escape, 2) Local radiation or certain chemotherapy induced immune suppression and
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surprisingly, 3) Vaccine induced immune suppression. In order to characterize and overcome these hurdles, they will address the following aims: 1) Analysis and development of methods to antagonize activated ras induced immune suppression and immune escape, 2) Analysis of the effects of clinically relevant local radiation and certain chemotherapies on the potency of therapeutic vaccines in these virus-induced tumor models in aging mice and, 3) Analysis and development of methods to antagonize peptide based vaccine induced immune suppression. To achieve these aims the following methodology will be used: 1a) Neutralizing TGFb induced by the activated ras oncogene, 1b) Blocking activated ras with farnesyl protein transferase inhibitors, as well as 1c) Defining a general antigen processing blocking effect by activated ras, and 1d) Characterizing other immune escape mechanisms induced in activated ras express cells. 2) Measuring the effects of local irradiation or certain chemotherapies on the potency of therapeutic vaccines to induce T cell responses in aging mice. 3A) Characterizing the immune suppression frequently induced by peptide based cancer vaccines through analyzing the pharmacokinetics of the vaccine components and, 3b) Converting immuno-suppressive peptide based cancer vaccines into immunizing vaccines by alternative delivery systems. This combined analysis will shed light on the immune suppression and immune escape mechanisms in the virus induced cancer models and on ways of counteracting them. Such mechanisms could also play a role in other clinically, relevant tumors. Therefore, the results could have direct implications on the design and execution of ongoing and future therapeutic cancer vaccine trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LATERAL FLOW ASSAY FOR ONCOGENIC STRAINS OF HPV Principal Investigator & Institution: Bazar, Leonard S.; Trevigen, Inc. 8405 Helgerman Ct Gaithersburg, Md 20877 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2003 Summary: (provided by applicant): Trevigen/TreviMed has developed the Mismatch Identification DNA Analysis System (MIDAS) that relies on SNIPase (geneticallyoptimized DNA mismatch repair enzymes) for the detection of pathogen DNA without the need for PCR amplification. The purpose of the research outlined in this Phase I proposal is to adapt MIDAS to a lateral-flow dipstick platform. To this end, we propose the following specific aims: (1) to design and test immobilized MIDAS probes to highrisk oncogenic strains of human papilloma virus (HPV strains 16 and 18) that incorporate biotin and various haptens such as dinitrophenyl (DNP), digoxigenin (DIG), fluorescein isothiocyanate (FITC), or bromodeoxyuridine (BrdU). In the presence of HPV target DNA and SNIPase, cleavage of the probe occurs, leading to the formation of a colored band on a lateral-flow dipstick. The MIDAS probes will be optimized initially with single-stranded oligonucleotides as targets, corresponding to HPV-16 and HPV-18 DNA sequences; (2) to optimize Dipstick-MIDAS for detecting the presence of cloned HPV-16 and HPV-18 DNA, and genomic DNA derived from HPV-16 and HPV-18positive cell lines. These efforts will culminate in a rapid, sensitive, multiplexed, costeffective, and accurate assay for oncogenic strains of HPV that cause cervical cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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
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Timing: Fiscal Year 2001; 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 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: MICROBICIDAL PEPTIDES TO PREVENT VIRAL STD INFECTION Principal Investigator & Institution: Brandt, Curtis R.; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Human Immunodeficiency Virus (HIV) is a serious public health threat. Other viral STDs including Herpes simplex virus (HSV) and Human Papilloma Virus (HPV) are also significant threats and the incidence of all three is rising rapidly. Infection with one viral STD can enhance acquisition of others. Since all three viruses cause persistent infection, once infected, the virus is not eliminated. Antivirals help but cannot clear the virus thus the most effective preventative strategy is to block infection. The applicant has identified a series of peptides that block infection with these viruses and the overall goal of this Program Project is to further development of these and other peptides for clinical use in preventing infection. The applicant will characterize the in vitro activity of the peptides, determine the mechanism of action, and measure in vitro toxicity. He will test structural variants to optimize the activity and when possible, test efficacy in appropriate animal models. The second goal of the Program is to use the existing and newly identified peptides as tools to study the process of viral infection. The Program Project consists of five components. Thee projects focus on specific viral STDs. A Peptide Design and Synthesis Core (Core A) directed by Dr. Brian Kay, will support the projects. An Administrative Core (Core B) directed by Dr. Brandt will oversee the Program. Project I, directed by Dr. Mirek
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Malkovsky, will focus on HIV. Project II, directed by Dr. Curtis Brandt, will focus on HSV, and Project III, directed by Dr. Paul Lambert will focus on HPV. The information gained by the proposed studies will be useful in moving the peptides toward clinical use as agents that can be included in a jelly applied by individuals to reduce or prevent sexual transmission of these viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR EPIDEMIOLOGY OF PERSISTENT HPV INFECTION Principal Investigator & Institution: Franco, Eduardo Lf.; Professor and Director; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2001; Project Start 11-SEP-1996; Project End 31-AUG-2003 Summary: This is a competing continuation application for continued study of human papilloma virus (HPV) genital persistent in a large cohort of low income women in Sao Paolo, Brazil, a high risk area for cervical carcinoma. The study focuses on the relationship of oncogenic HPV types on the development of cervical epithelial lesions and carcinoma. Participants undergo a series of questionnaire-based interviews to access sexual behavior and other potentially contributing factors, PAP smears, HPV testing by PCR, HPV serology and cervicography. The objectives are to 1 study incidence and prevalence of persistent cervical HPV in asymptomatic women; 2 verify the hypothesis that persistent HPV increases low and high grade cervical lesions; 3 detect epidemiological determinants of HPV persistence; 4 search for molecular variants associated with cervical lesions; 5 to determine whether HPV viral load is associated with persistence, and low or high grade lesions; and 6 study the role of antibody response to HPV persistence and lesion progression. For the competitive renewal, 2 additional aims are proposed: 7 identity HLA haplotypes associated with HPV persistence and cervical lesions; and 8 test whether p53 polymorphisms confer resistance to HPV persistence and lesion development. 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 94122 Timing: Fiscal Year 2001; Project Start 25-SEP-1991; Project End 31-JUL-2003 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 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
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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: PROSPECTIVE STUDY ON VIRAL LOAD OF CERVICAL CANCER Principal Investigator & Institution: Adami, Hans-Olov H.; Karolinska Institute Tomtebodavagen 11F Stockholm, 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
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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 •
Project Title: PROTEASES IN MODELS OF TUMOR INITIATION /PROGRESSION Principal Investigator & Institution: Werb, Zena; Professor and Vice Chair; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-JUN-2008 Summary: The aim of Project 3 is to investigate the role of metalloproteases in the development and progression of mouse epithelial cancers and to test the effects of antiprotease therapy in inhibiting these processes. By crossing transgenic models of cancer progression for the development and progression of mouse tumors into backgrounds that are null for specific proteases or protease inhibitors, or that over express specific protease inhibitors, it will be possible to determine when specific proteases or classes of proteases act, and which processes (growth, inflammation, invasion, metastasis, genomic instability) are downstream from protease action. In this funding cycle, the major focus of this project is to elucidate the contributions of individual active matrix metalloproteinases (MMPs) to neoplastic progression. We will concentrate on the human papilloma virus 16 early region targeted to the basal cells of the epidermis with the keratin 14 promoter, and, with Project 1, SV40 T-antigen targeted to prostatic epithelium with cryptidin-2 promoters. With CORE C, these will be crossed with mice on the same inbred background that are null or transgenic for specific metalloproteases or TIMPs, including MMP-2, MMP-3, MMP-9, MMP-13 and TIMP-1, alone and in specific double null combinations, and the impact on all aspects of progression from proliferation and apoptosis to influx of inflammatory cells, stromal activation, angiogenesis, matrix remodeling, malignant conversion, malignant grade and metastasis evaluated. In parallel, efficacy profiling of MMP inhibitor therapies will be done with Project 2. With CORES B and D expression patterns of the proteases and distribution of active proteases will be determined during progression in wild type mice, and then the impact of removing one MMP on the expression of other MMPs assessed. A major effort will be to seek the substrates that mediate these effects. The relative contributions of proteases from epithelial, inflammatory and/or stromal sources will be evaluated by transplanting neoplastic tissue or cells from one type of protease background onto animals of a distinct background. Angiogenesis, stromal activation and tumor development will then be assessed. Inactivating individual MMPs will likely have different effects than inhibiting the whole class of MMPs. Taken together, these model systems will elucidate the role of metalloproteases in the development of the premalignant lesions as well as in malignant conversion and metastasis, and provide proof-of-concept for anti-protease therapy in different stages of the development and progression of epithelial cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELECTION OF CHEMICAL INHIBITORS OF ONCOPROTEINS Principal Investigator & Institution: Bocchetta, Maurizio; Ob, Gyn, and Reproductive Med; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 25-MAY-2001; Project End 31-MAR-2003 Summary: (provided by applicant) Human Papilloma Viruses (HPVs) have been conclusively proven as causative agents of ano-genital tumors, and some tumors of the
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head and neck. A growing body of evidence relates Simian Virus 40 (SV40) with tumors of the mesothelium, brain, and bone. Both HPV and SV40 deregulate the p53 and pRb tumor suppressors pathways through binding of virus-encoded oncoproteins to the cellular p53 and pRb. Antisense technology targeting the HPV and SV40 oncoproteins leads to growth inhibition and apoptosis in cell lines derived from HPV-positive cervical cancers, and from SV40-positive malignant mesotheliomas, respectively. This evidence suggest that the HPV and SV40 oncoproteins represent valuable targets for the treatment of specific types of human cancer. Accordingly, both immuno-therapy and gene-therapy approaches to target HPV E6 and E7 are subjects of pre-clinical or clinical trials for the treatment of cervical cancer, and similar strategies have been proposed for the treatment of SV40-positive mesotheliomas. So far, immuno-therapy approaches have failed to provide a sufficient response in vivo, and genetic approaches are hampered by the lack of an efficient delivery system. We propose an alternative approach: the screening of chemical libraries to identify molecules capable of interfering with the binding of SV 40 and HPV oncoproteins to cellular p53 and pRb in vitro. These strategies require the analysis of a large panel of chemicals, a task feasible only if highthroughput assays to study the interactions of the viral oncoproteins with their cellular targets are available. These assays would require relatively high amounts of viral oncoproteins and tumor suppressors with proper post-translational modifications to ensure biological activity. Such requirement can be fulfilled if the protein substrates are expressed in human cells. However, human cell systems for protein over-expression are presently unavailable. We discovered that SV40-transformed human mesothelial cells (HM) can be used to obtain mg amounts of the SV40 large tumor antigen (Tag) in complex with cellular p53 and pRb. We propose to take advantage of this cell system to identify chemical inhibitors of the SV40 Tag-cellular tumor suppressors interactions. Moreover SV40-transformed mesothelial clones can be used as a basis to propagate "high copy number", episomal expression vectors in actively replicating human mesothelial ce!ls. Such vectors may allow over-expression of proteins requiring posttranslational modifications for proper biological activity in human cells. We propose to use this experimental system to overproduce and purify carrier-conjugable HPVl6 E6 and E7. Recombinant E6 and E7 will be subsequently used to develop ELISA-based in vitro assays to study the HPVl6 E6 and E7 binding to p53 and pRb, respectively. Finally, we propose to employ the latter assays for the screening of chemical libraries in order to find inhibitors of the HPV E6 and E7. The identification of putative inhibitors of the SV 40 and HPV oncoproteins may lead to the development of novel anticancer drugs. Furthermore, the experiments proposed may contribute novel technology for the overexpression and purification of potentially any protein in actively replicating human mesothelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL STUDIES OF PAPILLOMA VIRUSES Principal Investigator & Institution: Chen, Xiaojiang S.; Biochem & Molecular Genetics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: (Adapted from the Investigator's abstract): Papilloma viruses are DNA tumor viruses that infect higher vertebrates including humans. Human papilloma viruses (HPVs) include a group of "high-risk" viruses that are the major etiologic factor for cervical cancer and genital carcinoma. Thus, a structural analysis of papilloma viruses bears significant medical relevance The long term objectives of this proposal are to 1)
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determine the atomic structure of papilloma viruses in order to understand molecular mechanisms in capsid assembly and disassembly (uncoating), and 2) understand the structural basis of papilloma virus surface antigenicity, and the mechanisms of viral neutralization by antibodies. The specific aims build upon our recent determination of the atomic structure of the HPV16 L1 major capsid protein assembled m a T=1 structure. Structures of HPV11 and HPV5 L1 will be determined so that surface loop domains, predicted to be different between viral types, can be compared with the HPV16 structure. This comparison will help define the structural basis of surface antigenicity differences between viral subtypes, and may also provide insight into the location of the cell receptor binding sites. The interaction between viral surface epitopes and neutralizing antibodies will be studied by determining the structure of a complex between HPV 16 L1 and an Fab from a neutralizing monoclonal antibody. This structure will define antibody binding sites at high resolution and provide insight into the mechanism of viral neutralization. The structure of bovine papillomavirus will be determined to extend the current HPV16 structure from a T=1 to a complete T=7 particle. The complete virion structure will identify the contacts between "hexavalent" L1 pentamers as well as other bonds important for virion assembly (e.g. disulfide bonds). The structure of the minor capsid protein L2, in complex with L1 will be determined. This structure will define the domain of L2 that interacts with L1 and will hopefully provide initial information on how the L2 protein interacts with the viral genome and contributes to viral infectivity. Thus, these studies will not only provide information relevant to fundamental problems in structural virology but will also provide a basis for designing improved vaccines against papilloma viruses, and facilitating drug design to block viral entry and uncoating. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND ASSEMBLY OF VIRUSES Principal Investigator & Institution: Harrison, Stephen C.; Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2001; Project Start 01-JUN-1975; Project End 30-APR-2003 Summary: (Adapted from applicant's abstract): The long range goal is to study virus structure at high resolution, in order to describe mechanisms for viral entry and assembly and to provide a basis for vaccine and drug design. The proposal includes work on reoviruses and rotaviruses (both dsRNA viruses with related replication cycles) and on papillomaviruses. The rotaviruses are a major worldwide cause of childhood diarrhea. Certain papillomaviruses are strongly associated with human cervical cancer. (1) X-ray crystallographic studies of reovirus cores, "molecular machines" that modify and extrude mRNA, will be carried out at 3.3 A resolution. (2) The structure of the rotavirus "inner capsid particle" (ICP), homologous in many functions to the reovirus core, will also be determined crystallographically. Both the reovirus core and rotavirus ICP structures represent a significant level of molecular complexity (about 700 A diameter) and crystallographic challenge (over 1000 A unit cell dimensions). Strategies for collecting the diffraction data using synchrotron sources have been worked out; phase determination will use low-resolution structure from cryo-electron microscopy as starting points. (3) Expression and crystallization of the reovirus "penetration" protein, u1, and of the rotavirus attachment and penetration protein, VP4, will be undertaken, with high resolution crystal structures as the goal. The structures of these proteins will be analyzed in order to understand how non-enveloped viruses penetrate cell membranes. VP4 is also directly relevant to the development of rotavirus vaccines. (4) The structure of the human papilloma virus (HPV) L1 protein will be determined, using
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recombinant pentamers expressed in E. coli. This approach parallels work from the previous grant period on polyoma virus VP1, which HPV-L1 is likely to resemble. L1 is a major component of proposed recombinant HPV vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T CELL SIGNAL TRANSDUCTION TO MONITOR HPV VACCINES Principal Investigator & Institution: Ochoa, Augusto C.; Associate Professor; Pediatrics; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 30-SEP-2002 Summary: (Applicant's Abstract) Cancer vaccines and new combinations of chemotherapy and immunotherapy are actively being tested in numerous clinical trials based on the exciting results of the pre-clinical animal studies. However, previous results of immunotherapy trials and the recent findings on the immune response in cancer, suggest that these trials will encounter a major barrier, namely the immune dysfunction present in cancer patients. This immune dysfunction is manifested in vivo by the loss of a delayed type hypersensitivity (DTH), and in vitro by a decreased cytotoxicity, a diminished production of cytokines and the inability to respond to antigenic stimuli. The basis of these changes is unclear, although alterations in T cell function and signal transduction as well as changes in dendritic cell maturation have been demonstrated recently. It is however logical to think that a successful immunotherapy must correct these immunological alterations. The alterations in T cell function appear to be related to changes in the expression of T cell signal transduction molecules. These include a decreased expression of T cell receptor chain (TCR), a diminished level of p56lck and Jak-3 kinases and an inability to translocate NFkB p65 to the nucleus. These changes are not only seen in cancer patients, but also in patients with other diseases characterized by immune dysfunction such as leprosy. Preliminary results from clinical trials suggest that patients responding to the treatment, or developing an immune response to tumor antigens, recover the normal expression of T cell signal transduction molecules. In contrast patients with progressive tumor growth show persistent alterations in signal transduction proteins. Therefore this application proposes to 1) determine the signal transduction alterations present in T cells of patients with cervical cancer prior to and after vaccination with human papilloma virus (HPV) peptide vaccine 2) test whether these alterations are paralleled by changes in in vivo and in vitro T cell functions, and 3) determine whether the re-expression of T cell signal transduction proteins correlates with a successful vaccination or the induction of a clinical anti-tumor response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TBDN-1 AS A REGULATOR OF RETINAL ANGIOGENESIS Principal Investigator & Institution: Gendron, Robert L.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 16-NOV-2001 Summary: (Applicant's Description) Pathological neovascularization of the retina can cause vision loss and blindness. Inhibitors of angiogenesis present in normal eyes may be therapeutically useful to suppress abnormal blood vessel proliferation in diseased eyes. We have isolated a novel acetyltransferase, tubedown-1 (tbdn- 1), with proteinprotein interaction and DNA-binding motifs which is expressed exclusively in the corneal endothelium and in the limbic and retinal vascular endothelia in the normal eye. Tbdn-1 is absent or downregulated in blood vessels undergoing neovascularization in
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diseased and injured eyes. Inhibition of tbdn-1 stimulates angiogenesis in embryonic vascular endothelial cells in vitro, suggesting that tbdn-1 may be an angiogenesis inhibitor. These results together lead us to hypothesize that tbdn-1 may serve to inhibit angiogenesis in the normal eye. The goal of this project is to explore the functional role and potential utility of tbdn-1 as an inhibitor of retinal angiogenesis. Specific Aim 1: The functional role of tbdn-1 in retinal endothelial cells will be characterized. Tbdn-1 expression will be further studied in a model of retinopathy of prematurity and in specimens of proliferative diabetic retinopathy and macular degeneration. The effects of altering tbdn-1 expression levels on the angiogenic differentiation potential of retinal endothelial cells will be studied in vitro by overexpressing antisense and sense tbdn-1 cDNA in RF/6A rhesus retinal endothelial cell lines. Immortalized human retinal endothelial cell lines (HRVE) will be established using the human papilloma virus E7 protein, the human telomerase reverse transcriptase subunit (hTERT) or SV40 Large T antigen to provide in vitro model systems to further study and validate the functional role of tbdn-1 in human retinal vascular endothelium. Specific Aim 2: Functional activities of tbdn-1 in the context of retinal endothelial cells will be defined. This aim will explore the hypotheses that tbdn-1 inhibits angiogenesis in retinal endothelium through its acetylation activity, protein-protein interactions, DNA-binding activity or a combination of these. These properties will be examined in the specific context of angiogenesis of RF/6A cells or HRVE cells using an anti-tbdn-1 antibody and tbdn-lGST fusion protein. The findings of this project could indicate tbdn-1 as a potentially useful therapeutic target for treating eye diseases involving retinal neovascularization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF HPV IN SQUAMOUS CELL CARCINOMA Principal Investigator & Institution: Asgari, Maryam M.; Pathology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-JUL-2002 Summary: (Verbatim) - The aim of this study is to examine the association between human papilloma viruses (HPVs), p53 mutations and squamous cell carcinoma (SCC). There is a known association between certain genital HPV types (16 & 18) and genital malignancy. Such an association for HPV and cutaneous malignancy has been suggested by the rising incidence of SCCs in renal transplant recipients. However, no studies to date have shown a definitive association or pathogenesis. Preliminary data for cutaneous malignancy has shown that the potentially oncogenic HPV subtypes 5 and 8 that are found in skin do not exert their effect by inactivating p53 and RB proteins, which are inactivated by oncogenic genital HPVs. The hypothesis that is set forth in this study is that HPVs' role in the development of SCC is via clonal expansion. One hundred patients with SCC will be recruited to participate in this study. Biopsy specimens will be obtained from lesional, peri-lesional, and non-sun exposed skin to evaluate the relationship between HPV infections, p53 mutations, sun exposure, and the development of SCC. If certain HPV types are important for the pathogenesis of SCC, it may be possible to develop therapeutic HPV vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSFORMING GENES AND IMMUNOLOGICAL TUMOR REGRESSION Principal Investigator & Institution: Schreiber, Hans; Professor; Pathology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637
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Timing: Fiscal Year 2001; Project Start 10-JUL-1998; Project End 30-APR-2003 Summary: Transforming genes are essential for the development of cancer, and some of these genes encode strong antigens that can elicit tumor regression by CD+ T cells. One common goal of this Project is the identification of CTL- recognized peptide epitopes on antigens with such oncological and immunological, i.e. antigens encoded by human papilloma virus (HPV) and antigens found experimentally induced murine tumors. An additional goal of this Project is to understand how these CTL epitopes can be most effectively presented to the immune system. A final goal is to understand how cancer escape immune responses to these transforming proteins. Dr. Kast will explore the use of virus-like particles (VLPs) to immunize against products of transforming genes and plans to induce murine and human CD8+ T cells to transforming proteins of HPV, a major causative agent of human cervical cancer. Using experimental tumors as models, Dr. Schreiber will determine whether the unique antigens that are the prominent rejection antigen on chemically and physically induced tumors are due to somatic mutations (and thus truly tumor-specific), whether these mutant proteins have significance in the malignant process and whether unique antigens that are lost from and those that are retained by progressor tumors differ in oncogenic efforts in immunogenicity. Dr. Argon will explore the cell-biological mechanisms that allows hatshock proteins to bind and traffic viral or tumor-specific mutant peptides and "deliver" them to the MHC Class I molecules for presentation to CD8+ T cells. Finally, Dr. Meredith will give advice and guidance on the multiple biochemical aspects of the program and produce essential reagents. Together the three projects will define conditions and mechanism by which CD8+ T cell responses to peptides encoded by transforming genes lead to tumor destruction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIROLOGY AND CHRONIC INFECTION Principal Investigator & Institution: Botchan, Michael R.; Professor; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002 Summary: The Virology and Chronic Infection Research Core includes three investigators: Dr. Bruce Ames (now replaced by Dr. Mark Shigenaga), Drs. Michael Botchan and Robert Spear. Dr. Ames characterized mutagens produced by phagocytic cells, developed assays for DNA alterations produced by the mutagens, measured oxidative damage in DNA in a mouse model of chronic hepatitis, in collaboration with Dr. Frank Chisari at the Scripps Research Institute, and identified gamma tocopherol as a protective agent against DNA damage. He will continue to analyze the role of inflammation in cancer and will develop new methods for measuring chronic inflammatory damage to DNA and protein. Dr. Botchan characterized the DNA transcription and replication functions of bovine and human papilloma viruses (BPV and HPV). He showed that phosphorylation of the viral E2 protein regulates episome maintenance, and that E2 associates with mitotic chromosomes. He will attempt to solve the crystal structure of the HPV18 E2 activation domain, identify a chromosomal receptor for E1 and E2, and design compounds that block E1-E2 interactions. Dr. Spear identified a Chinese database useful for studying schistosome infection. He is using the database to study schistosomiasis disease prevalence and risk factors. He is developing methods for using satellite data to assess geographic conditions in areas such as the area of the "Three Gorges Dam," where ground surveys are difficult or impractical. He will continue to develop the remote sensing methods and will develop mathematical models that describe risk factors for schistosomiasis.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “human papilloma virus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for human papilloma virus in the PubMed Central database: •
Human Papilloma Virus DNAs Immortalize Normal Human Mammary Epithelial Cells and Reduce Their Growth Factor Requirements. by Band V, Zajchowski D, Kulesa V, Sager R.; 1990 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53284
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Human papilloma viruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences. by Klimov E, Vinokourova S, Moisjak E, Rakhmanaliev E, Kobseva V, Laimins L, Kisseljov F, Sulimova G.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134465
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Immortalization of Distinct Human Mammary Epithelial Cell Types by Human Papilloma Virus 16 E6 or E7. by Wazer DE, Liu X, Chu Q, Gao Q, Band V.; 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42026
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Induction of Cytotoxic T Lymphocytes with Peptides in vitro: Identification of Candidate T-Cell Epitopes in Human Papilloma Virus. by Stauss HJ, Davies H, Sadovnikova E, Chain B, Horowitz N, Sinclair C.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49816
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Inhibition of human papilloma virus E2 DNA binding protein by covalently linked polyamides. by Schaal TD, Mallet WG, McMinn DL, Nguyen NV, Sopko MM, John S, Parekh BS.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150225
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The Human Papilloma Virus 16E6 Gene Sensitizes Human Mammary Epithelial Cells to Apoptosis Induced by DNA Damage. by Xu C, Meikrantz W, Schlegel R, Sager R.; 1995 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41239
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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X-ray crystal structures of half the human papilloma virus E2 binding site: d(GACCGCGGTC). by Finley JB, Luo M.; 1998 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148040
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.6 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 human papilloma virus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “human papilloma virus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for human papilloma virus (hyperlinks lead to article summaries): •
A case of esophageal dysplasia associated with human papilloma virus. Author(s): Yoshikane H, Yokoi T, Suzuki T, Yoshioka N, Ogawa Y, Hamajima E. Source: The American Journal of Gastroenterology. 1995 August; 90(8): 1369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7639267&dopt=Abstract
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A comparative study on ultrastructure and immunological properties of human papilloma virus before and after fixation. Author(s): Kimura S, Harada R. Source: The Journal of Dermatology. 1982 April; 9(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6286744&dopt=Abstract
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A comparison of the ages of patients with cervical smears showing human papilloma virus, dysplasia and carcinoma in situ changes. Author(s): Chang AR. Source: N Z Med J. 1986 March 26; 99(798): 205-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3010201&dopt=Abstract
6 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 new mode of treatment of human papilloma virus associated anogenital lesions using a nonsteroid estrogen analogue. Author(s): Schon HJ, Grgurin M, Szekeres T, Schurz B. Source: Wiener Klinische Wochenschrift. 1996; 108(2): 45-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8835432&dopt=Abstract
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A novel type of human papilloma virus DNA from the lesion of epidermodysplasia verruciformis. Author(s): Adachi A, Yasue H, Ohashi M, Ishibashi M. Source: Japanese Journal of Cancer Research : Gann. 1986 October; 77(10): 978-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3023264&dopt=Abstract
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A randomized trial of laser vaporization in the management of cervical intraepithelial neoplasia associated with human papilloma virus infection. Author(s): Woodman CB, Byrne P, Kelly KA, Hilton C. Source: Journal of Public Health Medicine. 1993 December; 15(4): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7864916&dopt=Abstract
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A rapid DNA probe test for detecting human papilloma virus types 6/11 and 16 in biopsy specimens. Author(s): Todd JA, Jou L, Shen JT, Van Dinh T, Baker VV, Friedman AJ, Jacobs AJ, Krebs H, Posalaky Z, Runowicz C, et al. Source: Molecular and Cellular Probes. 1989 September; 3(3): 273-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2552303&dopt=Abstract
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A study comparing LETZ and CO2 laser treatment for cervical intra epithelial neoplasia with and without associated human papilloma virus. Author(s): Raju KS, Henderson E, Trehan A. Source: Eur J Gynaecol Oncol. 1995; 16(2): 92-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641744&dopt=Abstract
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A study of human papilloma virus DNA. Author(s): Crawford LV. Source: Journal of Molecular Biology. 1965 September; 13(2): 362-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4286353&dopt=Abstract
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A study of the relationship between ameloblastoma and human papilloma virus. Author(s): Namin AK, Azad TM, Eslami B, Sarkarat F, Shahrokhi M, Kashanian F. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2003 April; 61(4): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684965&dopt=Abstract
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A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions. Author(s): Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, van Ballegooijen M, van den Akker-van Marle E. Source: British Journal of Cancer. 2000 September; 83(5): 561-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10944591&dopt=Abstract
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Absence of human papilloma virus DNA in oropharyngeal spindle-cell squamous carcinomas. Author(s): Larsen ET, Duggan MA, Inoue M. Source: American Journal of Clinical Pathology. 1994 April; 101(4): 514-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160645&dopt=Abstract
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Absence of human papilloma virus in cervical adenocarcinoma determined by in situ hybridisation. Author(s): Young FI, Ward LM, Brown LJ. Source: Journal of Clinical Pathology. 1991 April; 44(4): 340-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1851501&dopt=Abstract
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Adenoid cystic carcinoma stage Ib1 treated with radical surgery displaying human papilloma virus 33 (HPV 33): immunoelectron microscopy and review. Author(s): Daponte A, Grayson W, Moisuc D, Ebrahim S, Guidozzi F. Source: Gynecologic Oncology. 2003 September; 90(3): 673-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678745&dopt=Abstract
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Allelic losses at chromosome 3p are seen in human papilloma virus 16 associated transitional cell carcinoma of the cervix. Author(s): Maitra A, Wistuba II, Gibbons D, Gazdar AF, Albores-Saavedra J. Source: Gynecologic Oncology. 1999 September; 74(3): 361-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479494&dopt=Abstract
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Alterations in growth properties of human papilloma virus type 16 immortalised human cervical keratinocyte cell line correlate with amplification and overexpression of c-myc oncogene. Author(s): Crook T, Greenfield I, Howard J, Stanley M. Source: Oncogene. 1990 April; 5(4): 619-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2158040&dopt=Abstract
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An expansive papilloma of the nasolachrymal drainage system harbouring human papilloma virus. Author(s): Buchwald C, Skoedt V, Tos M. Source: Rhinology. 1996 September; 34(3): 184-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938891&dopt=Abstract
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An immunoelectron microscopic localization of wart associated antigens present in human papilloma virus (HPV) infected cells. Author(s): Viac J, Schmitt D, Thivolet J. Source: The Journal of Investigative Dermatology. 1978 May; 70(5): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=205617&dopt=Abstract
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Anal verrucous carcinoma associated with human papilloma virus type 11: magnetic resonance imaging and flow cytometry evaluation. Author(s): Zemtsov A, Koss W, Dixon L, Tyring S, Rady P. Source: Archives of Dermatology. 1992 April; 128(4): 564-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1316107&dopt=Abstract
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Analysis of pregnancy and other factors on detection of human papilloma virus (HPV) infection using weighted estimating equations for follow-up data. Author(s): Ziegler A, Kastner C, Chang-Claude J. Source: Statistics in Medicine. 2003 July 15; 22(13): 2217-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820285&dopt=Abstract
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Analysis of the biological role of human papilloma virus (HPV)-encoded transcripts in cervical carcinoma cells by antisense RNA. Author(s): von Knebel Doeberitz M, Gissmann L. Source: Haematol Blood Transfus. 1987; 31: 377-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2450820&dopt=Abstract
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Analysis of the conformational change of recombinant human papilloma virus type 18 E7 protein induced by metal binding. Author(s): Kang JH, Jin SW, Yoon HS, Yoo WD, Kim HS, Hahm KS, Park SN. Source: Virus Research. 1997 June; 49(2): 147-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9213389&dopt=Abstract
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Analysis of the structure of human papilloma virus DNA. Author(s): DeLap RJ, Yanagi K, Rush MG. Source: Archives of Virology. 1977; 54(3): 263-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=196580&dopt=Abstract
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Anogenital human papilloma virus and the problem of persistence. Author(s): Syrjanen K. Source: Eur J Dermatol. 1998 October-November; 8(7 Suppl): 5-7; Discussion 20-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10387956&dopt=Abstract
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Antibody to human papilloma virus in Danish dentists. Author(s): Genner J, Scheutz F, Ebbesen P, Melbye M. Source: Scand J Dent Res. 1988 April; 96(2): 118-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2832934&dopt=Abstract
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Association between activated K-ras and c-erbB-2 oncogenes with “high-risk” and “low-risk” human papilloma virus types in preinvasive cervical lesions. Author(s): Mouron SA, Abba MC, Guerci A, Gomez MA, Dulout FN, Golijow CD. Source: Mutation Research. 2000 August 21; 469(1): 127-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946249&dopt=Abstract
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Association of Epstein-Barr virus, human papilloma virus, and cytomegalovirus with nine nasopharyngeal carcinoma cell lines. Author(s): Lin CT, Dee AN, Chen W, Chan WY. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1994 November; 71(5): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967524&dopt=Abstract
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Association of herpes simplex virus type-I and human papilloma virus with carcinoma of the oral cavity and oropharynx. Author(s): Ahmed S, Jafarey NA. Source: Journal of Environmental Pathology, Toxicology and Oncology : Official Organ of the International Society for Environmental Toxicology and Cancer. 1995; 14(3-4): 1936. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9003697&dopt=Abstract
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Association of human papilloma virus and Chlamydia trachomatis infections with incidence cervical neoplasia. Author(s): Cardillo MR. Source: Eur J Gynaecol Oncol. 1985; 6(3): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2996900&dopt=Abstract
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Atypical immature metaplasia (AIM). A subset of human papilloma virus infection of the cervix. Author(s): Crum CP, Egawa K, Fu YS, Lancaster WD, Barron B, Levine RU, Fenoglio CM, Richart RM. Source: Cancer. 1983 June 15; 51(12): 2214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6303548&dopt=Abstract
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Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases. Author(s): Cubilla AL, Reuter VE, Gregoire L, Ayala G, Ocampos S, Lancaster WD, Fair W. Source: The American Journal of Surgical Pathology. 1998 June; 22(6): 755-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9630184&dopt=Abstract
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Benign keratosis with a spectrum of follicular differentiation: a case series and investigation of a potential role of human papilloma virus. Author(s): Somach S, Morgan M. Source: Journal of Cutaneous Pathology. 2001 March; 28(3): 156-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11168769&dopt=Abstract
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Bilateral primary ovarian squamous cell carcinoma associated with human papilloma virus infection and vulvar and cervical intraepithelial neoplasia. A case report with review of the literature. Author(s): Mai KT, Yazdi HM, Bertrand MA, LeSaux N, Cathcart LL. Source: The American Journal of Surgical Pathology. 1996 June; 20(6): 767-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651358&dopt=Abstract
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Biotin and phosphorus-isotopic labelled DNA/RNA probes for the detection of human papilloma virus sequences. Author(s): Schon HJ, Czerwenka KF, Manavi M, Schatten C, Knogler W, Kubista E. Source: Wiener Klinische Wochenschrift. 1990 August 3; 102(15): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2169684&dopt=Abstract
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Caveolin-1 expression is down-regulated in cells transformed by the human papilloma virus in a p53-dependent manner. Replacement of caveolin-1 expression suppresses HPV-mediated cell transformation. Author(s): Razani B, Altschuler Y, Zhu L, Pestell RG, Mostov KE, Lisanti MP. Source: Biochemistry. 2000 November 14; 39(45): 13916-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076533&dopt=Abstract
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Cervical biopsy specimens and human papilloma virus positivity in patients with external genital warts. Author(s): Akdeniz S, Yaldiz M, Akdeniz N. Source: Eur J Gynaecol Oncol. 2002; 23(5): 460-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440827&dopt=Abstract
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Cervical human papilloma virus infection and colposcopy. Author(s): Chanen W. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1988 February; 28(1): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2850790&dopt=Abstract
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Cervical human papilloma virus infection and colposcopy. Author(s): Bonham DG, Green GH, Liggins GC. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1987 May; 27(2): 131. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2823782&dopt=Abstract
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Cervical human papilloma virus infection of women attending social hygiene clinics in Hong Kong. Author(s): Ngan HY, Collins RJ, Wong KY, Cheung A, Lai CF, Liu YT. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1993 April; 41(1): 75-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8098299&dopt=Abstract
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Cervical human papilloma virus infection: is treatment possible? Author(s): Benrubi GI, Shannon J, Glazer J, Nuss RC. Source: J Fla Med Assoc. 1988 December; 75(12): 799-800. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2850340&dopt=Abstract
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Cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant recipients. Author(s): Seshadri L, George SS, Vasudevan B, Krishna S. Source: Indian Journal of Cancer. 2001 June-December; 38(2-4): 92-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593446&dopt=Abstract
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Cervical intraepithelial neoplasia and human papilloma virus infection. Author(s): Seshadri L, Oomman M, Hemalatha K, Jairaj P. Source: Indian Journal of Cancer. 1991 March; 28(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1663073&dopt=Abstract
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Cervical neoplasia and human papilloma virus infection in prostitutes. Author(s): Gitsch G, Kainz C, Reinthaller A, Kopp W, Tatra G, Breitenecker G. Source: Genitourinary Medicine. 1991 December; 67(6): 478-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1663486&dopt=Abstract
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Cervical schistosomiasis, human papilloma virus (HPV), and human immunodeficiency virus (HIV): a dangerous coexistence or coincidence? Author(s): Mosunjac MB, Tadros T, Beach R, Majmudar B. Source: Gynecologic Oncology. 2003 July; 90(1): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821368&dopt=Abstract
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Characterization of human papilloma virus (H.P.V.) present in genital warts. Author(s): Staquet MJ, Viac J, Thivolet J, Chardonnet Y. Source: Archives of Dermatological Research. 1978 February 15; 261(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=205177&dopt=Abstract
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Characterization of primary human fibroblasts transformed by human papilloma virus type 16 and herpes simplex virus type 2 DNA sequences. Author(s): Dhanwada KR, Veerisetty V, Zhu F, Razzaque A, Thompson KD, Jones C. Source: The Journal of General Virology. 1992 April; 73 ( Pt 4): 791-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1321874&dopt=Abstract
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Chromosome 6p21.2, 18q21.2 and human papilloma virus (HPV) DNA can predict prognosis of cervical cancer after radiotherapy. Author(s): Harima Y, Sawada S, Nagata K, Sougawa M, Ohnishi T. Source: International Journal of Cancer. Journal International Du Cancer. 2001 October 20; 96(5): 286-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11582581&dopt=Abstract
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Clinical evaluation of a new model of self-obtained method for the assessment of genital human papilloma virus infection in an underserved population. Author(s): Chang CC, Tseng CJ, Liu WW, Jain S, Horng SG, Soong YK, Hsueh S, Pao CC. Source: Chang Gung Med J. 2002 October; 25(10): 664-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518778&dopt=Abstract
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Cloacogenic carcinoma of the anal canal and associated viral lesions. An in situ hybridization study for human papilloma virus. Author(s): Aparicio-Duque R, Mittal KR, Chan W, Schinella R. Source: Cancer. 1991 December 1; 68(11): 2422-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1657356&dopt=Abstract
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Cloning of E6 and E7 genes of human papilloma virus type 18 and transformation potential of E7 gene and its mutants. Author(s): Laassri M, Gul'ko L, Vinokurova S, Kisseljova N, Veiko V, Kisseljov F. Source: Virus Genes. 1999; 18(2): 139-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403700&dopt=Abstract
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Cold coagulation therapy in the treatment of histologically diagnosed subclinical human papilloma virus (HPV) infection of the cervix. Author(s): Mohanty KC, Lowe JW. Source: Br J Clin Pract. 1991 Summer; 45(2): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1665340&dopt=Abstract
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Colposcopy in the diagnosis of human papilloma virus infection, cervical intraepithelial neoplasia and invasive carcinoma. Author(s): Bajwa R, Khan SA, Qureshi GR, Chaudhry NA. Source: J Pak Med Assoc. 1993 December; 43(12): 257-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8133637&dopt=Abstract
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Comparative study of delayed hypersensitivity skin reactions and antibodies to human papilloma virus (HPV). Author(s): Viac J, Thivolet J, Hegazy MR, Chardonnet Y, Dambuyant C. Source: Clinical and Experimental Immunology. 1977 August; 29(2): 240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=198169&dopt=Abstract
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Comparison of smear specimens with biopsy specimens in a nucleic acid hybridization test for human papilloma virus (HPV) infection. Author(s): Auvinen E, Hukkanen V, Lehmijoki J, Salmi T, Arstila P. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1989; 68(7): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2561043&dopt=Abstract
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Comparison of the polymerase chain reaction and Southern blot analysis in detecting and typing human papilloma virus deoxyribonucleic acid in tumors of the lower female genital tract. Author(s): Monk BJ, Cook N, Ahn C, Vasilev SA, Berman ML, Wilczynski SP. Source: Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B. 1994 December; 3(4): 283-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7866640&dopt=Abstract
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Condyloma acuminatum and human papilloma virus infection in the oral mucosa of children. Author(s): Kui LL, Xiu HZ, Ning LY. Source: Pediatr Dent. 2003 March-April; 25(2): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723841&dopt=Abstract
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Congenital papillomas and papillomatoses associated with the human papilloma virus (HPV)-report on 5 cases. Author(s): Dias EP, Barcelos JM, Fonseca EF, Basso NG. Source: Rev Paul Med. 1995 July-August; 113(4): 957-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8729875&dopt=Abstract
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Correlation of modified human papilloma virus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. Author(s): von Knebel Doeberitz M, Oltersdorf T, Schwarz E, Gissmann L. Source: Cancer Research. 1988 July 1; 48(13): 3780-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837324&dopt=Abstract
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Cryotherapy in the management of histologically diagnosed subclinical human papilloma virus (HPV) infection of the cervix. Author(s): Mohanty KC, Lowe JW. Source: Br J Clin Pract. 1990 December; 44(12): 574-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1966312&dopt=Abstract
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Cumulation of TP53 mutations and p16INK4A/p15INK4B homozygous deletions in human papilloma virus type 16 positive scrotal cancer. Author(s): Guran S, Pak I. Source: Cancer Genetics and Cytogenetics. 1999 March; 109(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10087941&dopt=Abstract
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Cutaneous and mucous infections from human papilloma virus: new therapeutical approach. Author(s): Verardi S, Zupy E, Marconi D, Romanini C, Casciani CU. Source: Clin Ter. 2000; 151(1 Suppl 1): 35-52. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10876965&dopt=Abstract
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Cytokine induction and modifying the immune response to human papilloma virus with imiquimod. Author(s): Slade HB. Source: Eur J Dermatol. 1998 October-November; 8(7 Suppl): 13-6; Discussion 20-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10387958&dopt=Abstract
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Cytologic screening and human papilloma virus test in women undergoing artificial fertilization. Author(s): Lundqvist M, Westin C, Lundkvist O, Simberg N, Strand A, Andersson S, Wilander E. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 October; 81(10): 949-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366486&dopt=Abstract
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Cytology of high-grade squamous intraepithelial lesion in Japanese-Brazilian women with HIV infection with polymerase chain reaction-assisted human papilloma virus detection. Author(s): Kobayashi TK, Ueda M, Nishino T, Moritani S, Hanada Y, Mito K, Kushima R, Sata T. Source: Diagnostic Cytopathology. 2002 April; 26(4): 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933276&dopt=Abstract
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Demonstration of changes in cytokeratin expression in condylomata accuminata in relation to the presence of human papilloma virus as shown by a combination of immunohistochemistry and in situ hybridization. Author(s): Mullink H, Jiwa NM, Walboomers JM, Horstman A, Vos W, Meijer CJ. Source: The American Journal of Dermatopathology. 1991 December; 13(6): 530-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1725244&dopt=Abstract
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Demonstration of human papilloma virus (HPV) antigens in a case of urethral condyloma. Author(s): Syrjanen KJ, Pyrhonen S. Source: Scandinavian Journal of Urology and Nephrology. 1983; 17(3): 267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6316481&dopt=Abstract
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Demonstration of human papilloma virus antigen in the condylomatous lesions of the uterine cervix by immunoperoxidase technique. Author(s): Syrjanen KJ, Pyrhonen S. Source: Gynecologic and Obstetric Investigation. 1982; 14(2): 90-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6288519&dopt=Abstract
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Demonstration of human papilloma virus type 2 DNA in Bowen's disease. Author(s): Pfister H, Haneke E. Source: Archives of Dermatological Research. 1984; 276(2): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6326696&dopt=Abstract
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Detection and typing of human papilloma virus DNAs in normal cervix, intraepithelial neoplasia and cervical cancer in Bangkok. Author(s): Siritantikorn S, Laiwejpithaya S, Siripanyaphinyo U, Auewarakul P, Yenchitsomanus P, Thakernpol K, Wasi C. Source: Southeast Asian J Trop Med Public Health. 1997 December; 28(4): 707-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9656389&dopt=Abstract
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Detection of a human papilloma virus type 5 DNA in a renal allograft patient from Scotland. Author(s): Rudlinger R, Bunney MH, Smith IW, Hunter JA. Source: Dermatologica. 1988; 177(5): 280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2854081&dopt=Abstract
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Detection of herpes simplex virus and human papilloma virus in ophthalmic pterygium. Author(s): Detorakis ET, Sourvinos G, Spandidos DA. Source: Cornea. 2001 March; 20(2): 164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248821&dopt=Abstract
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Detection of herpes simplex virus type-2 DNA and human papilloma virus DNA sequences in cervical carcinoma tissue by molecular hybridization. Author(s): Thankamani V, Kumari TV, Vasudevan DM. Source: J Exp Pathol. 1992; 6(1-2): 55-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1320668&dopt=Abstract
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Detection of human papilloma virus (HPV) DNA in genital biopsy specimens by in situ hybridization with digoxigenin-labeled probes. Author(s): Heino P, Hukkanen V, Arstila P. Source: Journal of Virological Methods. 1989 December; 26(3): 331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2559923&dopt=Abstract
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Detection of human papilloma virus (HPV) genomes by the primed in situ (PRINS) labelling technique. Author(s): Ramael M, Van Steelandt H, Stuyven G, Van Steenkiste M, Degroote J. Source: Pathology, Research and Practice. 1999; 195(12): 801-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631714&dopt=Abstract
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Detection of human papilloma virus (HPV) in laryngeal carcinoma tissue. Author(s): Wang H, Lin YC, Kang XS, Li GZ, Li J, Liu BY, Qiao LJ, Ma KR. Source: Chinese Medical Journal. 1991 June; 104(6): 523-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1651831&dopt=Abstract
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Detection of human papilloma virus (HPV) infection in paraffin-embedded tissues of endometrial carcinoma. Author(s): Wong WS, Wong YF, Tam OS, Tam JS. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1993 May; 33(2): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8216121&dopt=Abstract
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Detection of human papilloma virus and Epstein-Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction. Author(s): Tung YC, Lin KH, Chu PY, Hsu CC, Kuo WR. Source: Kaohsiung J Med Sci. 1999 May; 15(5): 256-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375867&dopt=Abstract
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Detection of human papilloma virus DNA in lymph nodes extirpated at radical surgery for cervical cancer is not predictive of recurrence. Author(s): Czegledy J, Iosif C, Forslund O, Willen R, Hansson BG. Source: Journal of Medical Virology. 1998 March; 54(3): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9515766&dopt=Abstract
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Detection of human papilloma virus DNA in semen from patients with intrameatal penile warts. Author(s): Griffiths M. Source: Genitourinary Medicine. 1990 June; 66(3): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2164493&dopt=Abstract
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Detection of human papilloma virus DNA sequences by polymerase chain reaction. Author(s): Sarkar FH, Crissman JD. Source: Biotechniques. 1990 August; 9(2): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2169264&dopt=Abstract
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Detection of human papilloma virus DNA sequences in oral squamous cell papillomas by the polymerase chain reaction. Author(s): Ward KA, Napier SS, Winter PC, Maw RD, Dinsmore WW. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1995 July; 80(1): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7552864&dopt=Abstract
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Detection of human papilloma virus in women referred for colposcopy. A comparison between different diagnostic methods. Author(s): Boden E, Evander M, Wadell G, Bjersing L, von Schoultz B, Rylander E. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1990; 69(2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2166988&dopt=Abstract
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Detection of human papilloma virus infection in routine Papanicolaou-stained cervical smears. Author(s): Chakrabarti RN, Bhattacharya D, Sarkhel T. Source: Eur J Gynaecol Oncol. 1987; 8(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3032633&dopt=Abstract
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Detection of human papilloma virus type 16 DNA in oral squames from normal young adults. Author(s): Jalal H, Sanders CM, Prime SS, Scully C, Maitland NJ. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1992 November; 21(10): 465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1334148&dopt=Abstract
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Detection of human papilloma virus type 56 in extragenital Bowen's disease. Author(s): Uezato H, Hagiwara K, Ramuzi ST, Khaskhely NM, Nagata T, Nagamine Y, Nonaka S, Asato T, Oshiro M. Source: Acta Dermato-Venereologica. 1999 July; 79(4): 311-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10429991&dopt=Abstract
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Detection of human papilloma virus type 58 in a case of a perianal Bowen's disease coexistent with adult T-cell leukemia. Author(s): Uezato H, Hagiwara K, Maruno M, Ramuzi ST, Khaskhely NM, Oshiro M, Asato T, Nakashima Y, Nonaka S. Source: The Journal of Dermatology. 1999 March; 26(3): 168-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10209924&dopt=Abstract
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Detection of human papilloma virus type 6 DNA in an esophageal squamous cell papilloma. Author(s): Poljak M, Cerar A. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1994 February; 13(2): 1889. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8013499&dopt=Abstract
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Detection of human papilloma virus types 16 & 18 DNA in cervical lesions of Indian women using in situ hybridization. Author(s): Sarkar S, Verma K, Kaur H, Seth P. Source: The Indian Journal of Medical Research. 1992 December; 96: 356-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1337748&dopt=Abstract
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Detection of low level of human papilloma virus type 16 DNA sequences in cancer cell lines derived from two well-differentiated nasopharyngeal cancers. Author(s): Huang ES, Gutsch D, Tzung KW, Lin CT. Source: Journal of Medical Virology. 1993 July; 40(3): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8394875&dopt=Abstract
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Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma. Author(s): Wang J, Li J, Huang H, Fu Y. Source: Chin J Dent Res. 1998 December; 1(3): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10557171&dopt=Abstract
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Detection of the human papilloma virus type 16 mRNA-transcripts in cytological abnormal scrapings. Author(s): Falcinelli C, Claas E, Kleter B, Quint WG. Source: Journal of Medical Virology. 1992 June; 37(2): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1321226&dopt=Abstract
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Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells. Author(s): Rutz HP, Mariotta M, von Knebel Doeberitz M, Mirimanoff RO. Source: Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft. [et Al]. 1998 February; 174(2): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9487368&dopt=Abstract
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Differential regulation by c-jun and c-fos protooncogenes of hormone response from composite glucocorticoid response element in human papilloma virus type 16 regulatory region. Author(s): Mittal R, Kumar KU, Pater A, Pater MM. Source: Molecular Endocrinology (Baltimore, Md.). 1994 December; 8(12): 1701-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7708058&dopt=Abstract
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Does human papilloma virus have a role in squamous cell carcinoma of the colon and upper rectum? Author(s): Audeau A, Han HW, Johnston MJ, Whitehead MW, Frizelle FA. Source: European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2002 September; 28(6): 657-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359204&dopt=Abstract
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E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Author(s): Boyer SN, Wazer DE, Band V. Source: Cancer Research. 1996 October 15; 56(20): 4620-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840974&dopt=Abstract
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E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. Author(s): Wilding J, Vousden KH, Soutter WP, McCrea PD, Del Buono R, Pignatelli M. Source: Cancer Research. 1996 November 15; 56(22): 5285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8912870&dopt=Abstract
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Effect of oral aromatic retinoid (Ro 10-9359) on human papilloma virus-2-induced common warts. Author(s): Gross G, Pfister H, Hagedorn M, Stahn R. Source: Dermatologica. 1983; 166(1): 48-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6840376&dopt=Abstract
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Efficacy of cryotherapy in the treatment of human papilloma virus infection of the uterine cervix. Author(s): Benrubi G, Nuss RC, Holmes K, Lammert N. Source: J Fla Med Assoc. 1986 March; 73(3): 188-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3009684&dopt=Abstract
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Electronmicroscopic diagnosis of human papilloma virus in verruca plantaris. Author(s): Johnston FE, Meek WD, Henderson DA, McCosh J. Source: Journal of the American Podiatric Medical Association. 1995 June; 85(6): 306-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7541459&dopt=Abstract
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Endoscopic removal of esophageal condylomata acuminatum containing human papilloma virus. Author(s): Janson JA, Baillie J, Pollock M. Source: Gastrointestinal Endoscopy. 1991 May-June; 37(3): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1649063&dopt=Abstract
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Epidemiology of human papilloma virus infection. Author(s): Vogel LN. Source: Semin Dermatol. 1992 September; 11(3): 226-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1327055&dopt=Abstract
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Epidemiology of human papilloma virus infections and genital neoplasia. Author(s): Syrjanen K, Syrjanen S. Source: Scand J Infect Dis Suppl. 1990; 69: 7-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2175942&dopt=Abstract
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Epidermodysplasia verruciformis associated with type II human papilloma virus. Author(s): Sibrizzi JM, Estersohn HS, Gouterman IS. Source: Journal of the American Podiatric Medical Association. 1986 April; 76(4): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3009778&dopt=Abstract
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Esophageal papillomatosis from human papilloma virus proven by polymerase chain reaction. Author(s): Ravakhah K, Midamba F, West BC. Source: The American Journal of the Medical Sciences. 1998 October; 316(4): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9766491&dopt=Abstract
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Evaluation of adenoassociated virus 2 and human papilloma virus 16 and 18 infection in cervical cancer biopsies. Author(s): Ahn WS, Bae SM, Chung JE, Lee HK, Kim BK, Lee JM, Namkoong SE, Kim CK, Sin J. Source: Gynecologic Oncology. 2003 April; 89(1): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694662&dopt=Abstract
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Evaluation of male consorts of women with genital human papilloma virus infection. Author(s): Sand PK, Bowen LW, Blischke SO, Ostergard DR. Source: Obstetrics and Gynecology. 1986 November; 68(5): 679-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3763084&dopt=Abstract
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Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy. Author(s): Ozsaran AA, Ates T, Dikmen Y, Zeytinoglu A, Terek C, Erhan Y, Ozacar T, Bilgic A. Source: Eur J Gynaecol Oncol. 1999; 20(2): 127-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10376431&dopt=Abstract
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Evaluation of urinary cytology of male sexual partners of women with cervical intraepithelial neoplasia and human papilloma virus infection. Author(s): Nahhas WA, Marshall ML, Ponziani J, Jagielo JA. Source: Gynecologic Oncology. 1986 July; 24(3): 279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3013733&dopt=Abstract
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Evidence against diathermy as a beneficial treatment for human papilloma virus infection of the cervix. Author(s): Chanen W. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1990 August; 30(3): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2256869&dopt=Abstract
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Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: report of two cases and review of the literature. Author(s): Noel J, Lespagnard L, Fayt I, Verhest A, Dargent J. Source: Human Pathology. 2001 January; 32(1): 135-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172309&dopt=Abstract
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Experiments with human papilloma virus in cell culture. Author(s): Cubie HA. Source: The British Journal of Dermatology. 1974 November; 91(5): 569-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4373025&dopt=Abstract
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Expression of the different viral mRNAs of human papilloma virus 6 in a squamouscell carcinoma of the bladder and the cervix. Author(s): Oft M, Bohm S, Wilczynski SP, Iftner T. Source: International Journal of Cancer. Journal International Du Cancer. 1993 April 1; 53(6): 924-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8386138&dopt=Abstract
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Failure of the polymerase chain reaction (PCR) to detect human papilloma virus (HPV) in transitional cell carcinoma of the bladder. Author(s): Saltzstein DR, Orihuela E, Kocurek JN, Payne DA, Chan TS, Tyring SK. Source: Anticancer Res. 1993 March-April; 13(2): 423-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8390802&dopt=Abstract
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Failure to detect human papilloma virus in cutaneous molluscum contagiosum lesions. Author(s): Apisarnthanarax N, Payne D, Yen A, Tyring S. Source: Anticancer Res. 1997 November-December; 17(6D): 4781-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9494606&dopt=Abstract
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Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types. Author(s): Lai HC, Sun CA, Yu MH, Chen HJ, Liu HS, Chu TY. Source: International Journal of Cancer. Journal International Du Cancer. 1999 December 22; 84(6): 553-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10567897&dopt=Abstract
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Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16. Author(s): Collins LL, Lin DL, Mu XM, Chang C. Source: The Journal of Biological Chemistry. 2001 July 20; 276(29): 27316-21. Epub 2001 May 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358973&dopt=Abstract
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Fluorescent in situ PCR allows sensitive three hours detection of human papilloma virus in cells and tissues. Author(s): Marziliano N, Mancuso T, Comar M, Cernigoi E, Da Prato L, Garagna S, Boniotto M, Pirulli D, Puzzer D, Morgutti M, Amoroso A, Crovella S. Source: Eur J Histochem. 1999; 43(2): 155-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439218&dopt=Abstract
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Frequency of cervico-vaginal infections (Trichomonas vaginalis; Chlamydia trachomatis -CHL-; herpes simplex virus -HSV-; human papilloma virus -HPV-) in cervical intraepithelial neoplasia. Author(s): Alberico S, Facca MC, Di Bonito L, Millo R, Casaccia R, Mandruzzato GP. Source: Eur J Gynaecol Oncol. 1988; 9(3): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2839342&dopt=Abstract
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Fuchs' corneal endothelial cells transduced with the human papilloma virus E6/E7 oncogenes. Author(s): He Y, Weng J, Li Q, Knauf HP, Wilson SE. Source: Experimental Eye Research. 1997 July; 65(1): 135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9237874&dopt=Abstract
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Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. Author(s): Roecklein BA, Torok-Storb B. Source: Blood. 1995 February 15; 85(4): 997-1005. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7849321&dopt=Abstract
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Genital carriage of human papilloma virus (HPV) DNA in prepubertal girls with and without vulval disease. Author(s): Powell J, Strauss S, Gray J, Wojnarowska F. Source: Pediatric Dermatology. 2003 May-June; 20(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787264&dopt=Abstract
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Genital human papilloma virus infection in males. A clinico-pathologic study. Author(s): Koronel R, Stefanon B, Pilotti S, Bandieramonte G, Rilke F, De Palo G. Source: Tumori. 1991 February 28; 77(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1850179&dopt=Abstract
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Genital human papilloma virus infection in Oslo studied by dot blot DNA hybridization and the polymerase chain reaction. Author(s): Gjoen K, Siebke JC, Flikke M, Hager R, Ertzeid G, Halsos A, Ekgren J, Norling B, Grinde B, Orstavik I. Source: Journal of Medical Virology. 1991 July; 34(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1655965&dopt=Abstract
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Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status. Author(s): Mullokandov MR, Kholodilov NG, Atkin NB, Burk RD, Johnson AB, Klinger HP. Source: Cancer Research. 1996 January 1; 56(1): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8548763&dopt=Abstract
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Glucocorticoid-dependent oncogenic transformation by type 16 but not type 11 human papilloma virus DNA. Author(s): Pater MM, Hughes GA, Hyslop DE, Nakshatri H, Pater A. Source: Nature. 1988 October 27; 335(6193): 832-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2847052&dopt=Abstract
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Human papilloma virus (HPV) and cervical cancer. Author(s): Furumoto H, Irahara M. Source: J Med Invest. 2002 August; 49(3-4): 124-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12323001&dopt=Abstract
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Human papilloma virus (HPV) and p53 immunostaining in advanced tonsillar carcinoma--relation to radiotherapy response and survival. Author(s): Friesland S, Mellin H, Munck-Wikland E, Nilsson A, Lindholm J, Dalianis T, Lewensohn R. Source: Anticancer Res. 2001 January-February; 21(1B): 529-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299799&dopt=Abstract
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Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy. Author(s): Harima Y, Sawada S, Nagata K, Sougawa M, Ohnishi T. Source: International Journal of Radiation Oncology, Biology, Physics. 2002 April 1; 52(5): 1345-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955748&dopt=Abstract
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Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung carcinogenesis. Author(s): Gorgoulis VG, Zacharatos P, Kotsinas A, Kyroudi A, Rassidakis AN, Ikonomopoulos JA, Barbatis C, Herrington CS, Kittas C. Source: Human Pathology. 1999 March; 30(3): 274-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10088545&dopt=Abstract
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Human papilloma virus (HPV) type 16 and 18 detected in head and neck squamous cell carcinoma. Author(s): Mineta H, Ogino T, Amano HM, Ohkawa Y, Araki K, Takebayashi S, Miura K. Source: Anticancer Res. 1998 November-December; 18(6B): 4765-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891554&dopt=Abstract
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Human papilloma virus (HPV)-E6/E7 and epidermal growth factor receptor (EGF-R) protein levels in cervical cancer and cervical intraepithelial neoplasia (CIN). Author(s): Mathur SP, Mathur RS, Rust PF, Young RC. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2001 October; 46(4): 280-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642677&dopt=Abstract
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Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. Author(s): Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D, Band H, Band V. Source: The Journal of Biological Chemistry. 2002 November 22; 277(47): 45611-8. Epub 2002 September 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235159&dopt=Abstract
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Human papilloma virus 16 E7 oncogene does not cooperate with RET/PTC 3 oncogene in the neoplastic transformation of thyroid cells in transgenic mice. Author(s): Portella G, Borselli C, Santoro M, Gerbasio D, D'Armiento MR, Dumont JE, Ledent C, Rothstein JL, Vecchio G, Fusco A. Source: Oncology Research. 2000; 12(8): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589306&dopt=Abstract
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Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998. Author(s): Buchwald C, Lindeberg H, Pedersen BL, Franzmann MB. Source: The Laryngoscope. 2001 June; 111(6): 1104-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404629&dopt=Abstract
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Human papilloma virus and p53 in head and neck cancer: clinical correlates and survival. Author(s): Haraf DJ, Nodzenski E, Brachman D, Mick R, Montag A, Graves D, Vokes EE, Weichselbaum RR. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1996 April; 2(4): 755-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9816227&dopt=Abstract
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Human papilloma virus and P53 overexpression in carcinomas of the uterine cervix, lower uterine segment and endometrium. Author(s): Hachisuga T, Matsuo N, Iwasaka T, Sugimori H, Tsuneyoshi M. Source: Pathology. 1996 January; 28(1): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8714266&dopt=Abstract
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Human papilloma virus and squamous cell carcinomas of the head and neck. Author(s): Pradhan SA, Mulherkar R, Pai PS. Source: Natl Med J India. 2001 September-October; 14(5): 284. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767222&dopt=Abstract
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Human papilloma virus DNA detected in case of inverted squamous papilloma of the lacrimal sac. Author(s): Nakamura Y, Mashima Y, Kameyama K. Source: The British Journal of Ophthalmology. 1995 April; 79(4): 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7742294&dopt=Abstract
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Human papilloma virus DNA detection in oral lesions in the Greek population. Author(s): Aggelopoulou EP, Skarlos D, Papadimitriou C, Kittas C, Troungos C. Source: Anticancer Res. 1999 March-April; 19(2B): 1391-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10365111&dopt=Abstract
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Human papilloma virus DNA: a factor in the pathogenesis of mammary Paget's disease? Author(s): Czerwenka K, Heuss F, Hosmann JW, Manavi M, Lu Y, Jelincic D, Kubista E. Source: Breast Cancer Research and Treatment. 1996; 41(1): 51-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932876&dopt=Abstract
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Human papilloma virus E6 and E7 proteins support DNA replication of adenoviruses deleted for the E1A and E1B genes. Author(s): Steinwaerder DS, Carlson CA, Lieber A. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 September; 4(3): 211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545611&dopt=Abstract
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Human papilloma virus E6/E7 genes can expand the lifespan of human corneal fibroblasts. Author(s): Peters DM, Dowd N, Brandt C, Compton T. Source: In Vitro Cellular & Developmental Biology. Animal. 1996 May; 32(5): 279-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792157&dopt=Abstract
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Human papilloma virus has no prognostic significance in cervical carcinoma. Author(s): Kristensen GB, Karlsen F, Jenkins A, Kaern J, Abeler VM, Trope CG. Source: European Journal of Cancer (Oxford, England : 1990). 1996 July; 32A(8): 1349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8869098&dopt=Abstract
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Human papilloma virus in melanoma biopsy specimens and its relation to melanoma progression. Author(s): Dreau D, Culberson C, Wyatt S, Holder WD Jr. Source: Annals of Surgery. 2000 May; 231(5): 664-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767787&dopt=Abstract
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Human papilloma virus in verrucus carcinoma of the vulva: an immunopathological study of three cases. Author(s): Kondi-Paphitis A, Deligeorgi-Politi H, Liapis A, Plemenou-Frangou M. Source: Eur J Gynaecol Oncol. 1998; 19(3): 319-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9641242&dopt=Abstract
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Human papilloma virus infection and overexpression of p53 protein in bilharzial bladder cancer. Author(s): Khaled HM, Raafat A, Mokhtar N, Zekri AR, Gaballah H. Source: Tumori. 2001 July-August; 87(4): 256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693804&dopt=Abstract
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Human papilloma virus infection in the oral cavity--a source of infection. Author(s): Pec J, Filo V, Straka S, Baska T, Adamicova K, Pec M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1998 May; 10(3): 275-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9643338&dopt=Abstract
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Human papilloma virus infection of the vulva. Author(s): Beutner KR. Source: Semin Dermatol. 1996 March; 15(1): 2-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723818&dopt=Abstract
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Human papilloma virus proliferation in a healing burn. Author(s): Camilleri IG, Milner RH. Source: Burns : Journal of the International Society for Burn Injuries. 1996 March; 22(2): 162-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8634130&dopt=Abstract
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Human papilloma virus status and chromosomal imbalances in primary cervical carcinomas and tumour cell lines. Author(s): Hidalgo A, Schewe C, Petersen S, Salcedo M, Gariglio P, Schluns K, Dietel M, Petersen I. Source: European Journal of Cancer (Oxford, England : 1990). 2000 March; 36(4): 542-8. Erratum In: Eur J Cancer 2000 August; 36(12): 1587. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717534&dopt=Abstract
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Human papilloma virus testing in patient follow-up post cone biopsy due to highgrade cervical intraepithelial neoplasia. Author(s): Almog B, Gamzu R, Kuperminc MJ, Levin I, Fainaru O, Niv J, Bar-Am A. Source: Gynecologic Oncology. 2003 March; 88(3): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648585&dopt=Abstract
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Human papilloma virus type 16 E6 gene expression in oral exophytic epithelial lesions as detected by in situ rtPCR. Author(s): Al-Bakkal G, Ficarra G, McNeill K, Eversole LR, Sterrantino G, Birek C. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1999 February; 87(2): 197-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10052376&dopt=Abstract
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Human papilloma virus, vulvar dystrophy, and vulvar carcinoma: differential expression of human papillomavirus and vulvar dystrophy in the presence and absence of squamous cell carcinoma of the vulva. Author(s): Sagerman PM, Choi YJ, Hu Y, Niedt GW. Source: Gynecologic Oncology. 1996 June; 61(3): 328-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8641610&dopt=Abstract
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Human papilloma virus--H.P.V. condyloma. Current studies in diagnosis, treatment and prognosis. Author(s): Garrido JL. Source: Clin Exp Obstet Gynecol. 1996; 23(2): 99-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8737622&dopt=Abstract
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Humoral immune response against proteins E6 and E7 in cervical carcinoma patients positive for human papilloma virus type 16 during treatment and follow-up. Author(s): Baay MF, Duk JM, Burger MP, de Bruijn HW, Stolz E, Herbrink P. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1999 February; 18(2): 12632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219577&dopt=Abstract
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Identification of a novel human papilloma virus in cutaneous warts of meathandlers. Author(s): Ostrow RS, Krzyzek R, Pass F, Faras AJ. Source: Virology. 1981 January 15; 108(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6267773&dopt=Abstract
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Identification of human papilloma virus DNA sequence in the hyperplastic epithelium of an oral denture fibroma. Author(s): Yamaguchi T, Shindoh M, Amemiya A, Notani K, Fukuda H, Sakaoka H, Inoue M, Fujinaga K. Source: Disease Markers. 1997 April; 13(2): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160190&dopt=Abstract
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Identification of human papilloma virus in cervical swabs. Author(s): Okagaki T. Source: Obstetrics and Gynecology. 1985 November; 66(5): 746-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2997681&dopt=Abstract
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Identification of p53 and human papilloma virus in Schneiderian papillomas. Author(s): Mirza N, Montone K, Sato Y, Kroger H, Kennedy DW. Source: The Laryngoscope. 1998 April; 108(4 Pt 1): 497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9546259&dopt=Abstract
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Identification of the human papilloma virus-1a E4 gene products. Author(s): Doorbar J, Campbell D, Grand RJ, Gallimore PH. Source: The Embo Journal. 1986 February; 5(2): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3011404&dopt=Abstract
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Immortal, developmentally arrested human fetal kidney cell lines created by retroviral expression of human papilloma virus E6 and E7. Author(s): Drummond IA, Goodyer P, Sukhatme VP. Source: Experimental Nephrology. 1997 September-October; 5(5): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9386975&dopt=Abstract
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Immortalization of distinct human mammary epithelial cell types by human papilloma virus 16 E6 or E7. Author(s): Wazer DE, Liu XL, Chu Q, Gao Q, Band V. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 April 25; 92(9): 3687-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7537374&dopt=Abstract
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Immortalization of human adult prostatic adenocarcinoma cells by human papilloma virus HPV16 and -18 DNA. Author(s): Naghashfar Z, DiPaolo JA, Woodworth CD, Passaniti A. Source: Cancer Letters. 1996 February 27; 100(1-2): 47-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8620453&dopt=Abstract
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Immunocytochemical localization of human papilloma virus and cytomorphologic correlation in smears and biopsies of cervical flat condylomata. Author(s): Deligeorgi-Politi H, Mui KK, Trotta K, Safaii H, An-Foraker SH, Wolfe H, Hutchinson M. Source: Diagnostic Cytopathology. 1986 December; 2(4): 320-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3024936&dopt=Abstract
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Immunogenic properties of human papilloma virus type 16 (HPV-16) E5 polypeptide. Author(s): Gill D, Cason J, Punchard N. Source: Biochemical Society Transactions. 1997 May; 25(2): 281S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191325&dopt=Abstract
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Immunohistochemical demonstration of human papilloma virus (HPV) antigens in oral squamous cell lesions. Author(s): Syrjanen KJ, Pyrhonen S, Syrjanen SM, Lamberg MA. Source: Br J Oral Surg. 1983 June; 21(2): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6307342&dopt=Abstract
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Immunohistochemical demonstration of human papilloma virus antigen in human colon neoplasms. Author(s): Kirgan D, Manalo P, McGregor B. Source: The Journal of Surgical Research. 1990 May; 48(5): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2161968&dopt=Abstract
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Immunology of the human papilloma virus in relation to cancer. Author(s): Wu TC. Source: Current Opinion in Immunology. 1994 October; 6(5): 746-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7826530&dopt=Abstract
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Immunoperoxidase demonstration of human papilloma virus (HPV) in dysplastic lesions of the uterine cervix. Author(s): Syrjanen KJ, Pyrhonen S. Source: Arch Gynecol. 1982; 233(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6299212&dopt=Abstract
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Immunotherapy of gynaecological high-risk human papilloma virus infection with human leukocyte ultrafiltrate. Author(s): Spitzbart H, Hoyme UB. Source: Infectious Diseases in Obstetrics and Gynecology. 2000; 8(3-4): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968593&dopt=Abstract
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In situ localization of human papilloma virus type 16 DNA in a metastasis of an endocervical adenocarcinoma. Author(s): Walboomers JM, Fokke HE, Polak M, Volkers H, Houthoff HJ, Barents J, van der Noordaa J, ter Schegget J. Source: Intervirology. 1987; 27(2): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2822599&dopt=Abstract
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In vitro photodynamic treatment of normal and human papilloma virus-transfected keratinocytes with photofrin II and red light. Author(s): Bernstein EF, Glass JM, DeGraff WG, Schlegel R, Black C, Fisher JM, Cook SN, Glatstein E, Russo A, Mitchell JB. Source: Archives of Dermatology. 1991 May; 127(5): 683-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1850973&dopt=Abstract
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In vivo detection of human papilloma virus-induced lesions of anogenital area after application of acetic acid: a novel and accurate approach to a trivial method. Author(s): Stefanaki IM, Tosca AD, Themelis GC, Vazgiouraki EM, Dokianakis DN, Panayiotidis JG, Spandidos DA, Balas CJ. Source: Journal of Photochemistry and Photobiology. B, Biology. 2001 December 31; 65(2-3): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809368&dopt=Abstract
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Incidence of Gardnerella vaginalis, Candida sp and human papilloma virus in cytological smears. Author(s): Murta EF, Souza MA, Araujo Junior E, Adad SJ. Source: Sao Paulo Medical Journal = Revista Paulista De Medicina. 2000 July 6; 118(4): 105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10887386&dopt=Abstract
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Incidence of human papilloma virus in patients with invasive cervical carcinoma. Author(s): Sobti RC, Capalash N, Sehgal S, Gupta BD, Sharma P. Source: Cancer Genetics and Cytogenetics. 1996 June; 88(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8640731&dopt=Abstract
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Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Author(s): Jin L, Qi M, Chen DZ, Anderson A, Yang GY, Arbeit JM, Auborn KJ. Source: Cancer Research. 1999 August 15; 59(16): 3991-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10463597&dopt=Abstract
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Induction of proliferating cell nuclear antigen in cervical human papilloma virus lesions. Author(s): Mittal K. Source: Human Pathology. 1994 December; 25(12): 1375-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8001934&dopt=Abstract
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Inhibitors of epidermal growth factor receptor kinase and of cyclin-dependent kinase 2 activation induce growth arrest, differentiation, and apoptosis of human papilloma virus 16-immortalized human keratinocytes. Author(s): Ben-Bassat H, Rosenbaum-Mitrani S, Hartzstark Z, Shlomai Z, KleinbergerDoron N, Gazit A, Plowman G, Levitzki R, Tsvieli R, Levitzki A. Source: Cancer Research. 1997 September 1; 57(17): 3741-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288782&dopt=Abstract
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Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation. Author(s): Luscher-Firzlaff JM, Westendorf JM, Zwicker J, Burkhardt H, Henriksson M, Muller R, Pirollet F, Luscher B. Source: Oncogene. 1999 October 7; 18(41): 5620-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523841&dopt=Abstract
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Interferon alfa-2b for treatment of subclinical intraurethral human papilloma virus infection. Author(s): Harrison RH 3rd. Source: Urology. 1997 August; 50(2): 317. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9255317&dopt=Abstract
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Interferon in the treatment of human papilloma virus. Author(s): Strander HA. Source: The Medical Clinics of North America. 1986 May; Suppl: 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2426533&dopt=Abstract
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Interferon treatment enhances the expression of underphosphorylated (biologicallyactive) retinoblastoma protein in human papilloma virus-infected cells through the inhibitory TGF beta 1/IFN beta cytokine pathway. Author(s): Arany I, Rady P, Tyring SK. Source: Antiviral Research. 1994 February; 23(2): 131-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7511881&dopt=Abstract
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Intraepithelial neoplasia, human papilloma virus infection and argyrophilic nucleoprotein in cervical epithelium. Author(s): Egan M, Freeth M, Crocker J. Source: Histopathology. 1988 November; 13(5): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2850991&dopt=Abstract
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Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Author(s): Keating JT, Cviko A, Riethdorf S, Riethdorf L, Quade BJ, Sun D, Duensing S, Sheets EE, Munger K, Crum CP. Source: The American Journal of Surgical Pathology. 2001 July; 25(7): 884-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420459&dopt=Abstract
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Large atypical polyps of the vagina during pregnancy with concomitant human papilloma virus infection. Author(s): Maenpaa J, Soderstrom KO, Salmi T, Ekblad U. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1988 January; 27(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2828132&dopt=Abstract
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Localization of viral DNA-replication in sections of human warts by nucleic acid hybridization with complementary RNA of human papilloma virus Type 1. Author(s): Grussendorf EI, zur Hausen H. Source: Archives of Dermatological Research. 1979 February 23; 264(1): 55-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=220921&dopt=Abstract
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Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Author(s): Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA, Tsao MS. Source: American Journal of Pathology. 1996 June; 148(6): 1763-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8669463&dopt=Abstract
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Maintenance of vascular endothelial cell-specific properties after immortalization with an amphotrophic replication-deficient retrovirus containing human papilloma virus 16 E6/E7 DNA. Author(s): Fontijn R, Hop C, Brinkman HJ, Slater R, Westerveld A, van Mourik JA, Pannekoek H. Source: Experimental Cell Research. 1995 January; 216(1): 199-207. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7813621&dopt=Abstract
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Malignant progression of laryngeal papilloma associated with human papilloma virus type 6 (HPV-6) DNA. Author(s): Zarod AP, Rutherford JD, Corbitt G. Source: Journal of Clinical Pathology. 1988 March; 41(3): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2834418&dopt=Abstract
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Management of human papilloma virus vulvo-perineal infection with systemic betainterferon and thymostimulin in HIV-positive patients. Author(s): Frega A, di Renzi F, Stentella P, Pachi A. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1994 March; 44(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7909764&dopt=Abstract
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Medical therapy of genital human papilloma virus-related disease. Author(s): Lacey CJ, Fairley I. Source: International Journal of Std & Aids. 1995 November-December; 6(6): 399-407. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8845396&dopt=Abstract
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Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma. Author(s): Gissmann L, Diehl V, Schultz-Coulon HJ, zur Hausen H. Source: Journal of Virology. 1982 October; 44(1): 393-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6292500&dopt=Abstract
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Molecular cloning of a new human papilloma virus isolated from epidermodysplasia verruciformis lesions. Author(s): Tsumori T, Yutsudo M, Nakano Y, Tanigaki T, Kitamura H, Hakura A. Source: The Journal of General Virology. 1983 April; 64 (Pt 4): 967-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6300314&dopt=Abstract
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Molecular diagnosis of persistent human papilloma virus infections. Author(s): Wieland U, Pfister H. Source: Intervirology. 1996; 39(3): 145-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9058167&dopt=Abstract
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Morphological and immunohistochemical evidence of human papilloma virus (HPV) involvement in the dysplastic lesions of the uterine cervix. Author(s): Syrjanen K, Vayrynen M, Castren O, Mantyjarvi R, Pyrhonen S, Yliskoski M. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1983 August; 21(4): 261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6141079&dopt=Abstract
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Mucosal immunoglobulin-A and -G responses to oncogenic human papilloma virus capsids. Author(s): Sasagawa T, Rose RC, Azar KK, Sakai A, Inoue M. Source: International Journal of Cancer. Journal International Du Cancer. 2003 April 10; 104(3): 328-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569556&dopt=Abstract
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Multichannel piezoelectric genesensor for the detection of human papilloma virus. Author(s): Wang J, Fu W, Liu M, Wang Y, Xue Q, Huang J, Zhu Q. Source: Chinese Medical Journal. 2002 March; 115(3): 439-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940384&dopt=Abstract
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Multilineage differentiation of adult human bone marrow progenitor cells transduced with human papilloma virus type 16 E6/E7 genes. Author(s): Osyczka AM, Noth U, O'Connor J, Caterson EJ, Yoon K, Danielson KG, Tuan RS. Source: Calcified Tissue International. 2002 November; 71(5): 447-58. Epub 2002 September 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12232673&dopt=Abstract
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Multiple Bowen's disease of the fingers associated with human papilloma virus type 16. Author(s): McGrae JD Jr, Greer CE, Manos MM. Source: International Journal of Dermatology. 1993 February; 32(2): 104-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8382665&dopt=Abstract
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Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man. Author(s): Malcolm K, Meschede W, Pawlita M, Koutsky LA, Frazer IH. Source: Intervirology. 2000; 43(3): 165-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044810&dopt=Abstract
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Multiple metachronous skin squamous cell carcinomas and epidermodysplasia verruciformis in the head region: a human papilloma virus-associated disease. Author(s): Weber BP, Fierlbeck G, Kempf HG. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1994; 251(6): 342-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7848644&dopt=Abstract
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Need for national register to monitor cervical human papilloma virus infection. Author(s): Shaw V, Say PJ. Source: N Z Med J. 1988 March 9; 101(841): 123. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837708&dopt=Abstract
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New human papilloma virus isolated from epidermodysplasia verruciformis lesions. Author(s): Yutsudo M, Tanigaki T, Tsumori T, Watanabe S, Hakura A. Source: Cancer Research. 1982 June; 42(6): 2440-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6280858&dopt=Abstract
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Non radioactive in situ hybridization for detection of human papilloma virus DNA in squamous cell carcinoma of tongue. Author(s): Honig JF. Source: Bull Group Int Rech Sci Stomatol Odontol. 1992 September-December; 35(3-4): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1338425&dopt=Abstract
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Non-isotopic in situ hybridization of human papilloma virus on histologic sections: an amended protocol. Author(s): Orosz Z, Udvarhelyi N, Szentirmay Z. Source: Anticancer Res. 1994 September-October; 14(5A): 1991-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7847839&dopt=Abstract
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Nucleotide sequence and phylogenetic classification of candidate human papilloma virus type 92. Author(s): Forslund O, Antonsson A, Higgins G, Ly H, Delius H, Hunziker A, de Villiers EM. Source: Virology. 2003 August 1; 312(2): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919731&dopt=Abstract
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p53 alteration and human papilloma virus infection in paranasal sinus cancer. Author(s): Caruana SM, Zwiebel N, Cocker R, McCormick SA, Eberle RC, Lazarus P. Source: Cancer. 1997 April 1; 79(7): 1320-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083153&dopt=Abstract
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p53 and human papilloma virus type 16 in cervical intraepithelial neoplasia and carcinoma. Author(s): ter Harmsel B, van Belkum A, Quint W, Pronk A, Kuijpers J, Ramaekers F, Tandon A, Smedts F. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 1995 April; 14(2): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8601524&dopt=Abstract
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P53 codon 72 polymorphism and susceptibility to development of human papilloma virus-associated cervical cancer in Indian women. Author(s): Nagpal JK, Sahni S, Das BR. Source: European Journal of Clinical Investigation. 2002 December; 32(12): 943-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534455&dopt=Abstract
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Pathological incidence study of human papilloma virus (HPV) carried out on 1,439 patients between 1982-1985 in Panama. Author(s): Garrido JL. Source: Eur J Gynaecol Oncol. 1988; 9(2): 144-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2838282&dopt=Abstract
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PCR-RFLP-detected human papilloma virus infection in a group of senegalese women attending an STD clinic and identification of a new HPV-68 subtype. Author(s): Astori G, Beltrame A, Pipan C, Raphenon G, Botta GA. Source: Intervirology. 1999; 42(4): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10567840&dopt=Abstract
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Penile cancer and human papilloma virus (HPV) in a human immunodeficiency virus (HIV)-infected patient. Author(s): Aboulafia DM, Gibbons R. Source: Cancer Investigation. 2001; 19(3): 266-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338884&dopt=Abstract
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Penile intraepithelial neoplasia in patients examined for exposure to human papilloma virus. Author(s): Zabbo A, Stein BS. Source: Urology. 1993 January; 41(1): 24-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8380511&dopt=Abstract
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Persistence of viral DNA in human cell cultures infected with human papilloma virus. Author(s): Lancaster WD, Meinke W. Source: Nature. 1975 July 31; 256(5516): 434-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=167292&dopt=Abstract
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Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions. Author(s): Tonon SA, Picconi MA, Bos PD, Zinovich JB, Galuppo J, Alonio LV, Teyssie AR. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2001 May; 21(2): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378493&dopt=Abstract
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Prediction of human papilloma virus antigen in cervical squamous epithelium by koilocyte nuclear morphology and “wart scores”: confirmation by immunoperoxidase. Author(s): McLeod K. Source: Journal of Clinical Pathology. 1987 March; 40(3): 323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3031136&dopt=Abstract
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Predictors of human papilloma virus in patients with keratinization. Author(s): Hudock J, Hanau CA, Hawthorne C, Jordan AG. Source: Diagnostic Cytopathology. 1995 February; 12(1): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7540530&dopt=Abstract
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Preferential chromosome loss in human papilloma virus DNA-immortalized mammary epithelial cells. Author(s): Swisshelm K, Leonard M, Sager R. Source: Genes, Chromosomes & Cancer. 1992 October; 5(3): 219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1384674&dopt=Abstract
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Preferential retention of the E6 and E7 regions of the human papilloma virus type 18 genome by human sperm cells. Author(s): Pao CC, Yang FP, Lai YM. Source: Fertility and Sterility. 1996 October; 66(4): 630-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8816629&dopt=Abstract
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Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes. Author(s): Kobayashi Y, Yoshinouchi M, Tianqi G, Nakamura K, Hongo A, Kamimura S, Mizutani Y, Kodama J, Miyagi Y, Kudo T. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1998 April; 4(4): 979-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9563893&dopt=Abstract
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Presence of human papilloma virus in transitional cell carcinoma in Jewish population in Israel. Author(s): Smetana Z, Keller T, Leventon-Kriss S, Huszar M, Lindner A, MitraniRosenbaum S, Mendelson E, Smetana S. Source: Cell Mol Biol (Noisy-Le-Grand). 1995 December; 41(8): 1017-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8747082&dopt=Abstract
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Presence of human papilloma virus in tumor tissue from children with retinoblastoma: an alternative mechanism for tumor development. Author(s): Orjuela M, Castaneda VP, Ridaura C, Lecona E, Leal C, Abramson DH, Orlow I, Gerald W, Cordon-Cardo C. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2000 October; 6(10): 4010-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11051250&dopt=Abstract
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Presence of human papilloma virus type 16 DNA sequences in human nonmelanoma skin cancers. Author(s): Pierceall WE, Goldberg LH, Ananthaswamy HN. Source: The Journal of Investigative Dermatology. 1991 November; 97(5): 880-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1919051&dopt=Abstract
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Presence of human papilloma virus types 16 and 18 in genital warts and cervical neoplasias. Author(s): Battista C, Hillova J, Hill M, Reynes M, Mathe G. Source: Med Oncol Tumor Pharmacother. 1988; 5(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2835559&dopt=Abstract
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Preservation of the myofibroblastic phenotype of human papilloma virus 16 E6/E7 immortalized human bone marrow cells using the lineage limited alpha-smooth muscle actin promoter. Author(s): Loeuillet C, Douay L, Herve P, Chalmers DE. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 2001 May; 12(5): 233-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11373270&dopt=Abstract
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Prevalence and cytologic manifestations of human papilloma virus (HPV) types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56 among 500 consecutive women. Author(s): Kiviat NB, Koutsky LA, Critchlow CW, Lorincz AT, Cullen AP, Brockway J, Holmes KK. Source: International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists. 1992 July; 11(3): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1328077&dopt=Abstract
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Prevalence of condylomatous atypia and human papilloma virus antigen in cervical biopsies in 1972 and 1983. Author(s): Kock KF, Johansen P. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1987; 66(2): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3039785&dopt=Abstract
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Prevalence of high-risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma (OSCC) patients of Eastern India. Author(s): Nagpal JK, Patnaik S, Das BR. Source: International Journal of Cancer. Journal International Du Cancer. 2002 February 10; 97(5): 649-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807792&dopt=Abstract
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Prevalence of human papilloma virus 16 or 18 in cervical cancer in Hualien, eastern Taiwan. Author(s): Hsu YH, Wei TC, Horng IJ, Jan WC, Su IJ. Source: Kaohsiung J Med Sci. 1997 May; 13(5): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9226973&dopt=Abstract
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Prevalence of human papilloma virus DNA in head and neck cancers carrying wildtype or mutant p53 tumor suppressor genes. Author(s): Adams V, Schmid S, Zariwala M, Schmid M, Kleihues P, Briner J, Schafer R. Source: Anticancer Res. 1999 January-February; 19(1A): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10226517&dopt=Abstract
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Prevalence of human papilloma virus genital infections in sexually transmitted diseases clinic attendees in Ibadan. Author(s): Okesola AO, Fawole OI. Source: West Afr J Med. 2000 July-September; 19(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126083&dopt=Abstract
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Prevalence of human papilloma virus in men attending the infertility clinic. Author(s): Pakendorf UW, Bornman MS, Du Plessis DJ. Source: Andrologia. 1998 February-March; 30(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9567165&dopt=Abstract
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Prognostic importance of human papilloma virus typing in squamous cell papilloma of the bronchus: comparison of in situ hybridization and the polymerase chain reaction. Author(s): Popper HH, el-Shabrawi Y, Wockel W, Hofler G, Kenner L, Juttner-Smolle FM, Pongratz MG. Source: Human Pathology. 1994 November; 25(11): 1191-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7959664&dopt=Abstract
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Prospective evaluation of risk of cervical cancer after cytological evidence of human papilloma virus infection. Author(s): Mitchell H, Drake M, Medley G. Source: Lancet. 1986 March 15; 1(8481): 573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2869301&dopt=Abstract
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Prospective study of antibody to human papilloma virus type 16 and risk of cervical, endometrial, and ovarian cancers (United States). Author(s): Hisada M, van den Berg BJ, Strickler HD, Christianson RE, Wright WE, Waters DJ, Rabkin CS. Source: Cancer Causes & Control : Ccc. 2001 May; 12(4): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456229&dopt=Abstract
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Purification and characterization of the plantar human papilloma virus. Author(s): Abramson C, Fischman GJ. Source: Journal of the American Podiatric Medical Association. 1987 March; 77(3): 12333. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3033196&dopt=Abstract
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Recent developments in understanding the immune response to human papilloma virus infection and cervical neoplasia. Author(s): Kobayashi A, Miaskowski C, Wallhagen M, Smith-McCune K. Source: Oncology Nursing Forum. 2000 May; 27(4): 643-51; Quiz 652-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833693&dopt=Abstract
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Recurrent laryngeal papillomatosis developing into laryngeal carcinoma with human papilloma virus (HPV) type 18: a case report. Author(s): Sakakura A, Yamamoto Y, Takasaki T, Makimoto K, Nakamura M, Takahashi H. Source: The Journal of Laryngology and Otology. 1996 January; 110(1): 75-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745789&dopt=Abstract
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Regression of esophageal papillomatous polyposis caused by high-risk type human papilloma virus. Author(s): Kato H, Orito E, Yoshinouchi T, Ueda R, Koizumi T, Yoshinouchi M, Mizokami M. Source: Journal of Gastroenterology. 2003; 38(6): 579-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856674&dopt=Abstract
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Relevance of photo-immunosuppression for viral infections (i.e. human papilloma virus). Author(s): Vermeer BJ, Bouwes Bavinck JN. Source: Eur J Dermatol. 1998 April-May; 8(3): 205-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9649706&dopt=Abstract
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Reproductive and sexual risk factors and human papilloma virus infection in cervical cancer among Hong Kong Chinese. Author(s): Donnan SP, Wong FW, Ho SC, Lau EM, Takashi K, Esteve J. Source: International Journal of Epidemiology. 1989 March; 18(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2542172&dopt=Abstract
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Role of herpes simplex virus type-2 and human papilloma virus in penile cancers in Singapore. Author(s): Raju GC, Lee YS. Source: Ann Acad Med Singapore. 1987 July; 16(3): 550-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2829697&dopt=Abstract
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Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy. Author(s): Jastreboff AM, Cymet T. Source: Postgraduate Medical Journal. 2002 April; 78(918): 225-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930025&dopt=Abstract
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Selective detection of human papilloma virus DNAs by specific synthetic DNA probes. Author(s): Cravador A, Herzog A, Houard S, d'Ippolito P, Carroll R, Bollen A. Source: Molecular and Cellular Probes. 1989 June; 3(2): 143-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2549406&dopt=Abstract
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Selective suppression of human papilloma virus type 18 mRNA level in HeLa cells by interferon. Author(s): Nawa A, Nishiyama Y, Yamamoto N, Maeno K, Goto S, Tomoda Y. Source: Biochemical and Biophysical Research Communications. 1990 July 31; 170(2): 793-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1696477&dopt=Abstract
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Sensitivity of in situ detection with biotinylated probes of human papilloma virus type 16 DNA in frozen tissue sections of squamous cell carcinomas of the cervix. Author(s): Walboomers JM, Melchers WJ, Mullink H, Meijer CJ, Struyk A, Quint WG, van der Noordaa J, ter Schegget J. Source: American Journal of Pathology. 1988 June; 131(3): 587-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2837906&dopt=Abstract
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Sequence variation in the early genes E1E4, E6 and E7 of human papilloma virus type 6. Author(s): Krige D, Mills HR, Berrie EL, Doherty NC, Jones DK, Ryan CA, Davies H, Myint S, McCance DJ, Layton GT, French TJ. Source: Virus Research. 1997 June; 49(2): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9213393&dopt=Abstract
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Seroepidemiological studies of human papilloma virus (HPV-1) infections. Author(s): Pfister H, zur Hausen H. Source: International Journal of Cancer. Journal International Du Cancer. 1978 February 15; 21(2): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=203545&dopt=Abstract
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Serological studies in a student population prone to infection with human papilloma virus. Author(s): Cubie HA. Source: J Hyg (Lond). 1972 December; 70(4): 677-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4346010&dopt=Abstract
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Seven-color time-resolved fluorescence hybridization analysis of human papilloma virus types. Author(s): Samiotaki M, Kwiatkowski M, Ylitalo N, Landegren U. Source: Analytical Biochemistry. 1997 November 15; 253(2): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9367497&dopt=Abstract
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Sexually transmitted diseases. Part III: recent developments in sexually transmitted diseases: Centers for Disease Control's new treatment schedule from the viewpoint of a private practitioner: viral infections (human papilloma virus, herpes simplex virus) gonorrhea, chlamydia-nongonococcal urethritis. Author(s): Felman YM. Source: Cutis; Cutaneous Medicine for the Practitioner. 1990 May; 45(5): 295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2162751&dopt=Abstract
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Simultaneous detection by consensus multiplex PCR of high- and low-risk and other types of human papilloma virus in clinical samples. Author(s): Zheng PS, Li SR, Iwasaka T, Song J, Cui MH, Sugimori H. Source: Gynecologic Oncology. 1995 August; 58(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7622102&dopt=Abstract
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Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors. Author(s): Di Luca D, Rotola A, Pilotti S, Monini P, Caselli E, Rilke F, Cassai E. Source: International Journal of Cancer. Journal International Du Cancer. 1987 December 15; 40(6): 763-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2826337&dopt=Abstract
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So-called multicentric pigmented Bowen's disease. Report of a case and a possible etiologic role of human papilloma virus. Author(s): Kimura S, Hirai A, Harada R, Nagashima M. Source: Dermatologica. 1978; 157(4): 229-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=211056&dopt=Abstract
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Solid phase cytometry allows rapid in situ quantification of human papilloma virus infection in biopsy material. Author(s): Butor C, Duquenne O, Mignon-Godefroy K, Mougin C, Guillet JG. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1997 December 1; 29(4): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415411&dopt=Abstract
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Solitary squamous papilloma of the bronchus associated with human papilloma virus type 11. Author(s): Kawaguchi T, Matumura A, Iuchi K, Yamamoto S, Inoue Y, Sunami T, Naka N, Okishio K, Ueno K, Atagi S, Ogawara M, Hosoe S, Kawahara M. Source: Intern Med. 1999 October; 38(10): 817-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10526947&dopt=Abstract
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Specific immunity in patients suffering from recurring warts before and after repetitive intradermal tests with human papilloma virus. Author(s): Viac J, Thivolet J, Chardonnet Y. Source: The British Journal of Dermatology. 1977 October; 97(4): 365-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=201265&dopt=Abstract
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Specific immunity to human papilloma virus (HPV) in patients with genital warts. Author(s): Viac J, Staquet MJ, Miguet M, Chabanon M, Thivolet J. Source: Br J Vener Dis. 1978 June; 54(3): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=207383&dopt=Abstract
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Squamous cell papilloma of the esophagus: a tumour probably caused by human papilloma virus (HPV). Author(s): Syrjanen K, Pyrhonen S, Aukee S, Koskela E. Source: Diagn Histopathol. 1982 October-December; 5(4): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6188592&dopt=Abstract
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Studies with human papilloma virus modeled after known papovavirus systems. Author(s): Butel JS. Source: Journal of the National Cancer Institute. 1972 February; 48(2): 285-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4347032&dopt=Abstract
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Study of sequences of DNA of the human papilloma virus genotypes 6 and 16 in patients with cancer of vulva and cervix uteri. Author(s): Bokhman JV, Kuznetsov OK, Maximov SJ, Tadzhibayeva JT, Aron PA, Vasilyev BV, Migunova BV, Tkeshmelashvili VG. Source: Clin Exp Obstet Gynecol. 1990; 17(3-4): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1963384&dopt=Abstract
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Subclinical human papilloma virus infection in condylomata acuminata patients attending a VD clinic. Author(s): Sand Petersen C, Albrectsen J, Larsen J, Sindrup J, Tikjob G, Ottevanger V, Karlsmark T, Fogh H, Mellon Mogensen A, Wolff-Sneedorff A. Source: Acta Dermato-Venereologica. 1991; 71(3): 252-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1678233&dopt=Abstract
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Suppression of senescence in normal human fibroblasts by introduction of dominantnegative p53 mutants or human papilloma virus type 16 E6 protein. Author(s): Ide A, Fujii M, Nakababashi K, Ayusawa D. Source: Bioscience, Biotechnology, and Biochemistry. 1998 July; 62(7): 1458-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720232&dopt=Abstract
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Suppression of tumorigenesis by transcription units expressing the antisense E6 and E7 messenger RNA (mRNA) for the transforming proteins of the human papilloma virus and the sense mRNA for the retinoblastoma gene in cervical carcinoma cells. Author(s): Hu G, Liu W, Hanania EG, Fu S, Wang T, Deisseroth AB. Source: Cancer Gene Therapy. 1995 March; 2(1): 19-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7621252&dopt=Abstract
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T cell epitopes in human papilloma virus proteins. Author(s): Sadovnikova E, Stauss HJ. Source: Behring Inst Mitt. 1994 July; (94): 87-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7528003&dopt=Abstract
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The absence of human papilloma virus (HPV) related parameters in sexually nonactive women. Author(s): Peters AA, Trimbos JB. Source: Eur J Gynaecol Oncol. 1994; 15(1): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8206070&dopt=Abstract
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The association between cervical carcinoma and human papilloma virus (HPV) in Xiangyuan County. Author(s): Zhang W, Sun Y, Jin S, Liang X, Ming L, Wang X, Shang M, Wu A, Wang X, Sun J, et al. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1991 June; 6(2): 74-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1666523&dopt=Abstract
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The Brn-3a transcription factor plays a critical role in regulating human papilloma virus gene expression and determining the growth characteristics of cervical cancer cells. Author(s): Ndisang D, Budhram-Mahadeo V, Latchman DS. Source: The Journal of Biological Chemistry. 1999 October 1; 274(40): 28521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10497216&dopt=Abstract
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The clinical role of human papilloma virus typing. Author(s): Sedlacek TV, Sedlacek AE, Neff DK, Rando RF. Source: Gynecologic Oncology. 1991 September; 42(3): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1659553&dopt=Abstract
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The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Author(s): Li S, Labrecque S, Gauzzi MC, Cuddihy AR, Wong AH, Pellegrini S, Matlashewski GJ, Koromilas AE. Source: Oncogene. 1999 October 14; 18(42): 5727-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523853&dopt=Abstract
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The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage. Author(s): Xu C, Meikrantz W, Schlegel R, Sager R. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 August 15; 92(17): 7829-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7644500&dopt=Abstract
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The human papilloma virus E7 oncoprotein inhibits transforming growth factor-beta signaling by blocking binding of the Smad complex to its target sequence. Author(s): Lee DK, Kim BC, Kim IY, Cho EA, Satterwhite DJ, Kim SJ. Source: The Journal of Biological Chemistry. 2002 October 11; 277(41): 38557-64. Epub 2002 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145312&dopt=Abstract
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The immunology of genital human papilloma virus infection. Author(s): Stanley M. Source: Eur J Dermatol. 1998 October-November; 8(7 Suppl): 8-12; Discussion 20-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10387957&dopt=Abstract
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The management of minor degrees of cervical dysplasia associated with the human papilloma virus. Author(s): Carmichael JA. Source: Yale J Biol Med. 1991 November-December; 64(6): 591-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1667239&dopt=Abstract
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The predictive value of human papilloma virus (HPV) typing in the prognosis of bronchial squamous cell papillomas. Author(s): Popper HH, Wirnsberger G, Juttner-Smolle FM, Pongratz MG, Sommersgutter M. Source: Histopathology. 1992 October; 21(4): 323-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1328017&dopt=Abstract
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The prevalence of human papilloma virus DNA in women with mucopurulent endocervicitis. Author(s): Altuglu I, Terek MC, Ozacar T, Ozsaran AA, Bilgic A. Source: Eur J Gynaecol Oncol. 2002; 23(2): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013119&dopt=Abstract
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The role of the human papilloma virus in esophageal cancer. Author(s): Sur M, Cooper K. Source: Pathology. 1998 November; 30(4): 348-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839308&dopt=Abstract
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The status of the p53 gene in human papilloma virus positive or negative cervical carcinoma cell lines. Author(s): Srivastava S, Tong YA, Devadas K, Zou ZQ, Chen Y, Pirollo KF, Chang EH. Source: Carcinogenesis. 1992 July; 13(7): 1273-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1322252&dopt=Abstract
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The theoretical population-level impact of a prophylactic human papilloma virus vaccine. Author(s): Hughes JP, Garnett GP, Koutsky L. Source: Epidemiology (Cambridge, Mass.). 2002 November; 13(6): 631-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410003&dopt=Abstract
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Transactivation of the human papilloma virus 16 octamer motif by the octamer binding protein Oct-2 requires both the N and C terminal activation domains. Author(s): Morris PJ, Ring CJ, Lillycrop KA, Latchman DS. Source: Nucleic Acids Research. 1993 September 25; 21(19): 4506-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8233784&dopt=Abstract
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Transitional cell and uncommon urothelial carcinoma of renal pelvis/ureter and bladder: low incidence of human papilloma virus. Author(s): Wang JS, Tseng HH, Lin SL, Hsieh SP. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1997 March; 59(3): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9198289&dopt=Abstract
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Transitional cell papilloma of the penis associated with human papilloma virus infection. Report of two cases. Author(s): Rodriguez-Pinilla SM, Rodriguez-Peralto JL, Fernandez-Figueras MT. Source: Virchows Archiv : an International Journal of Pathology. 2003 June; 442(6): 6014. Epub 2003 May 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728314&dopt=Abstract
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Treatment of human papilloma virus in a 6-month-old infant with imiquimod 5% cream. Author(s): Schaen L, Mercurio MG. Source: Pediatric Dermatology. 2001 September-October; 18(5): 450-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737697&dopt=Abstract
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Treatment of subclinical intraurethral human papilloma virus infection with interferon alfa-2b. Author(s): Levine LA, Elterman L, Rukstalis DB. Source: Urology. 1996 April; 47(4): 553-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8638367&dopt=Abstract
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Trophoblasts are the preferential target for human papilloma virus infection in spontaneously aborted products of conception. Author(s): Hermonat PL, Kechelava S, Lowery CL, Korourian S. Source: Human Pathology. 1998 February; 29(2): 170-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9490277&dopt=Abstract
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Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16. Author(s): Gunn GR, Zubair A, Peters C, Pan ZK, Wu TC, Paterson Y. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 December 1; 167(11): 64719. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714814&dopt=Abstract
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Typing of common human papilloma virus strains by multiplex PCR. Author(s): Lazarus P, Caruana S. Source: Analytical Biochemistry. 1996 December 1; 243(1): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8954550&dopt=Abstract
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Tyrphostins that suppress the growth of human papilloma virus 16-immortalized human keratinocytes. Author(s): Ben-Bassat H, Rosenbaum-Mitrani S, Hartzstark Z, Levitzki R, Chaouat M, Shlomai Z, Klein BY, Kleinberger-Doron N, Gazit A, Tsvieli R, Levitzki A. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 September; 290(3): 1442-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454524&dopt=Abstract
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Ultrastructural localization of human papilloma virus by nonradioactive in situ hybridization on tissue of human cervical intraepithelial neoplasia. Author(s): Multhaupt HA, Rafferty PA, Warhol MJ. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1992 October; 67(4): 512-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1331611&dopt=Abstract
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Uptake of exogenous human papilloma virus L1 DNA by oocytes and detection by the polymerase chain reaction. Author(s): Chan PJ, Su BC, Tredway DR, Seraj M, Seraj IM, King A. Source: Journal of Assisted Reproduction and Genetics. 1992 December; 9(6): 531-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1338579&dopt=Abstract
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Urethral condylomata, due to human papilloma virus (HPV) type 6/11., associated with transitional cell tumors in the bladder and ureter. A case report. Author(s): Olsen S, Marcussen N, Jensen KM, Lindeberg H. Source: Scand J Urol Nephrol Suppl. 1995; 172: 51-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8578257&dopt=Abstract
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Use of anticontamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies. Author(s): van den Brule AJ, Claas EC, du Maine M, Melchers WJ, Helmerhorst T, Quint WG, Lindeman J, Meijer CJ, Walboomers JM. Source: Journal of Medical Virology. 1989 September; 29(1): 20-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2555442&dopt=Abstract
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Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases. Author(s): Infantolino C, Fabris P, Infantolino D, Biasin MR, Venza E, Tositti G, Minucci D. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2000 November; 93(1): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11000508&dopt=Abstract
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UV-vulnerability of human papilloma virus type-16 E7-expressing astrocytes is associated with mitochondrial membrane depolarization and caspase-3 activation. Author(s): Lee WT, Lee SH, Carriedo SG, Giffard RG, Yoon YJ, Kim JH, Park KA, Lee JE. Source: Molecules and Cells. 2002 October 31; 14(2): 288-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442903&dopt=Abstract
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Viral etiology of cervical carcinoma. Human papilloma virus and herpes simplex virus type 2. Author(s): Meng XJ, Sun Y, Chen MH, Liu ZH, Zhang YX, Li XZ, Li K, Han RC, Si JY, Hu LY, et al. Source: Chinese Medical Journal. 1989 February; 102(2): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2550184&dopt=Abstract
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Viral integration sites in human papilloma virus-33-immortalized cervical keratinocyte cell lines. Author(s): Gilles C, Piette J, Ploton D, Doco-Fenzy M, Foidart JM. Source: Cancer Genetics and Cytogenetics. 1996 August; 90(1): 63-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8780750&dopt=Abstract
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Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Author(s): Josefsson AM, Magnusson PK, Ylitalo N, Sorensen P, Qwarforth-Tubbin P, Andersen PK, Melbye M, Adami HO, Gyllensten UB. Source: Lancet. 2000 June 24; 355(9222): 2189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881891&dopt=Abstract
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Vulvar intraepithelial neoplasia: correlation of nuclear DNA content and the presence of a human papilloma virus (HPV) structural antigen. Author(s): Crum CP, Braun LA, Shah KV, Fu YS, Levine RU, Fenoglio CM, Richart RM, Townsend DE. Source: Cancer. 1982 February 1; 49(3): 468-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6277449&dopt=Abstract
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Warts and cancer: the oncogenic potential of human papilloma virus. Author(s): Lynch PJ. Source: The American Journal of Dermatopathology. 1982 February; 4(1): 55-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6282149&dopt=Abstract
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Widespread elevated expression of the human papilloma virus (HPV)-activating cellular transcription factor Brn-3a in the cervix of women with CIN3 (cervical intraepithelial neoplasia stage 3). Author(s): Ndisang D, Budhram-Mahadeo V, Singer A, Latchman DS. Source: Clinical Science (London, England : 1979). 2000 May; 98(5): 601-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10781392&dopt=Abstract
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CHAPTER 2. NUTRITION AND HUMAN PAPILLOMA VIRUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and human papilloma virus.
Finding Nutrition Studies on Human Papilloma Virus The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “human papilloma virus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “human papilloma virus” (or a synonym): •
Biotin and phosphorus-isotopic labelled DNA/RNA probes for the detection of human papilloma virus sequences. Author(s): Institute of Medical Chemistry, University of Vienna. Source: Schon, H J Czerwenka, K F Manavi, M Schatten, C Knogler, W Kubista, E WienKlin-Wochenschr. 1990 August 3; 102(15): 449-54 0043-5325
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Cervical human papilloma virus infection: is treatment possible? Source: Benrubi, G I Shannon, J Glazer, J Nuss, R C J-Fla-Med-Assoc. 1988 December; 75(12): 799-800 0015-4148
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Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator. Author(s): Division of Radiation and Cancer Biology, Department of Radiation Oncology, New England Medical Center, Boston, Massachusetts 02111, USA. Source: Zeng, M KuMarch, A Meng, G Gao, Q Dimri, G Wazer, D Band, H Band, V JBiol-Chem. 2002 November 22; 277(47): 45611-8 0021-9258
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In vivo detection of human papilloma virus-induced lesions of anogenital area after application of acetic acid: a novel and accurate approach to a trivial method. Author(s): Department of Dermatology, Heraklion University General Hospital, 71110 Crete, Greece.
[email protected] Source: Stefanaki, I M Tosca, A D Themelis, G C Vazgiouraki, E M Dokianakis, D N Panayiotidis, J G Spandidos, D A Balas, C J J-Photochem-Photobiol-B. 2001 December 31; 65(2-3): 115-21 1011-1344
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Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Author(s): Department of Otolaryngology, Long Island Jewish Medical Center, The Long Island Campus of Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA. Source: Jin, L Qi, M Chen, D Z Anderson, A Yang, G Y Arbeit, J M Auborn, K J CancerRes. 1999 August 15; 59(16): 3991-7 0008-5472
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Intraepithelial neoplasia, human papilloma virus infection and argyrophilic nucleoprotein in cervical epithelium. Author(s): Department of Histopathology, Wolverhampton Royal Hospital, UK. Source: Egan, M Freeth, M Crocker, J Histopathology. 1988 November; 13(5): 561-7 03090167
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Prevalence of human papilloma virus genital infections in sexually transmitted diseases clinic attendees in Ibadan. Author(s): Department of Medical Microbiology and Parasitology, UCH, Ibadan. Source: Okesola, A O Fawole, O I West-Afr-J-Med. 2000 Jul-September; 19(3): 195-9 0189160X
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Sensitivity of in situ detection with biotinylated probes of human papilloma virus type 16 DNA in frozen tissue sections of squamous cell carcinomas of the cervix. Author(s): Department of Pathology, Free University Hospital, Amsterdam, The Netherlands. Source: Walboomers, J M Melchers, W J Mullink, H Meijer, C J Struyk, A Quint, W G van der Noordaa, J ter Schegget, J Am-J-Pathol. 1988 June; 131(3): 587-94 0002-9440
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Synthesis in vitro and application of biotinylated DNA probes for human papilloma virus type 16 by utilizing the polymerase chain reaction. Author(s): Department of Clinical Chemistry, University of Birmingham, Edgbaston, U.K. Source: Day, P J Bevan, I S Gurney, S J Young, L S Walker, M R Biochem-J. 1990 April 1; 267(1): 119-23 0264-6021
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Synthetic oligonucleotide probes for the detection of human papilloma viruses by in situ hybridisation. Author(s): Department of Bacteriology, University of Edinburgh Medical School, U.K. Source: Cubie, H A Norval, M J-Virol-Methods. 1988 July; 20(3): 239-49 0166-0934
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The human papilloma virus 16E6 gene sensitizes human mammary epithelial cells to apoptosis induced by DNA damage. Author(s): Division of Cancer Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Source: Xu, C Meikrantz, W Schlegel, R Sager, R Proc-Natl-Acad-Sci-U-S-A. 1995 August 15; 92(17): 7829-33 0027-8424
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Ultrastructural localization of human papilloma virus by nonradioactive in situ hybridization on tissue of human cervical intraepithelial neoplasia. Author(s): Department of Pathology, Pennsylvania Hospital, Philadelphia. Source: Multhaupt, H A Rafferty, P A Warhol, M J Lab-Invest. 1992 October; 67(4): 512-8 0023-6837
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND HUMAN PAPILLOMA VIRUS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to human papilloma virus. 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 human papilloma virus 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 “human papilloma virus” (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 human papilloma virus: •
A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression. Author(s): Ahn WS, Huh SW, Bae SM, Lee IP, Lee JM, Namkoong SE, Kim CK, Sin JI. Source: Dna and Cell Biology. 2003 March; 22(3): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804120&dopt=Abstract
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Absence of human papillomavirus DNA from esophageal carcinoma as determined by multiple broad spectrum polymerase chain reactions. Author(s): Smits HL, Tjong-A-Hung SP, ter Schegget J, Nooter K, Kok T. Source: Journal of Medical Virology. 1995 July; 46(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561792&dopt=Abstract
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Adolescent behavior and sexually transmitted diseases: the dilemma of human papillomavirus. Author(s): Cothran MM, White JP. Source: Health Care for Women International. 2002 April-May; 23(3): 306-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003506&dopt=Abstract
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Anal and penile condylomas in HIV-negative and HIV-positive men: clinical, histological and virological characteristics correlated to therapeutic outcome. Author(s): von Krogh G, Wikstrom A, Syrjanen K, Syrjanen S. Source: Acta Dermato-Venereologica. 1995 November; 75(6): 470-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8651027&dopt=Abstract
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Apoptosis mediates the selective toxicity of caffeic acid phenethyl ester (CAPE) toward oncogene-transformed rat embryo fibroblast cells. Author(s): Su ZZ, Lin J, Prewett M, Goldstein NI, Fisher PB. Source: Anticancer Res. 1995 September-October; 15(5B): 1841-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8572568&dopt=Abstract
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Arsenic trioxide induces apoptosis of HPV16 DNA-immortalized human cervical epithelial cells and selectively inhibits viral gene expression. Author(s): Zheng J, Deng YP, Lin C, Fu M, Xiao PG, Wu M. Source: International Journal of Cancer. Journal International Du Cancer. 1999 July 19; 82(2): 286-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389765&dopt=Abstract
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Autogenous vaccine: the best therapy for perianal condyloma acuminata? Author(s): Wiltz OH, Torregrosa M, Wiltz O. Source: Diseases of the Colon and Rectum. 1995 August; 38(8): 838-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7634978&dopt=Abstract
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Biologic activity of oligonucleotides with polarity and anomeric center reversal. Author(s): Tan TM, Kalisch BW, van de Sande JH, Ting RC, Tan YH. Source: Antisense & Nucleic Acid Drug Development. 1998 April; 8(2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9593047&dopt=Abstract
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Cadherin-mediated adhesion is required for normal growth regulation of human gingival epithelial cells. Author(s): Kandikonda S, Oda D, Niederman R, Sorkin BC. Source: Cell Adhes Commun. 1996 July; 4(1): 13-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8870970&dopt=Abstract
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Cervical human papilloma virus infection: is treatment possible? Author(s): Benrubi GI, Shannon J, Glazer J, Nuss RC.
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Source: J Fla Med Assoc. 1988 December; 75(12): 799-800. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2850340&dopt=Abstract •
Circulating nucleosomes and response to chemotherapy: an in vitro, in vivo and clinical study on cervical cancer patients. Author(s): Trejo-Becerril C, Perez-Cardenas E, Trevino-Cuevas H, Taja-Chayeb L, Garcia-Lopez P, Segura-Pacheco B, Chavez-Blanco A, Lizano-Soberon M, GonzalezFierro A, Mariscal I, Wegman-Ostrosky T, Duenas-Gonzalez A. Source: International Journal of Cancer. Journal International Du Cancer. 2003 May 10; 104(6): 663-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640671&dopt=Abstract
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Clinical course and prognostic factors of human papillomavirus infections in men. Author(s): Hippelainen MI, Hippelainen M, Saarikoski S, Syrjanen K. Source: Sexually Transmitted Diseases. 1994 September-October; 21(5): 272-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7817261&dopt=Abstract
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Combination therapy with podophyllin and vidarabine for human papillomavirus positive cervical intraepithelial neoplasia. Author(s): Okamoto A, Woodworth CD, Yen K, Chung J, Isonishi S, Nikaido T, Kiyokawa T, Seo H, Kitahara Y, Ochiai K, Tanaka T. Source: Oncol Rep. 1999 March-April; 6(2): 269-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022988&dopt=Abstract
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Comparison of women with cervical human papillomavirus infection and genital warts. I. Some behavioural factors and clinical findings. Author(s): Hellberg D, Borendal N, Sikstrom B, Nilsson S, Mardh PA. Source: Genitourinary Medicine. 1995 April; 71(2): 88-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7744420&dopt=Abstract
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Detection of HPV in genital condylomata: correlation between viral load and clinical outcome. Author(s): De Marco F, Di Carlo A, Poggiali F, Muller A, Marcante ML. Source: J Exp Clin Cancer Res. 2001 September; 20(3): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718218&dopt=Abstract
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Differential behavior of VEGF receptor expression and response to TNP-470 in two immortalized human endothelial cell lines. Author(s): Seki M, Toi M, Kobayashi K, Shitara K, Umezawa K, Seon BK, Kan M, Rhim JS. Source: International Journal of Oncology. 2000 September; 17(3): 525-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10938394&dopt=Abstract
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Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Author(s): Fan S, Smith ML, Rivet DJ 2nd, Duba D, Zhan Q, Kohn KW, Fornace AJ Jr, O'Connor PM. Source: Cancer Research. 1995 April 15; 55(8): 1649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7712469&dopt=Abstract
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Drug watch. Author(s): Whitson S. Source: Posit Aware. 1999 May-June; 10(3): 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11366758&dopt=Abstract
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Efficacy of surgical and/or podophyllotoxin treatment against flat acetowhite penile human papillomavirus associated lesions. Author(s): Wikstrom A, von Krogh G. Source: International Journal of Std & Aids. 1998 September; 9(9): 537-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9764938&dopt=Abstract
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Enhancement of EGF- and PMA-mediated MAP kinase activation in cells expressing the human papillomavirus type 16 E5 protein. Author(s): Crusius K, Auvinen E, Alonso A. Source: Oncogene. 1997 September 18; 15(12): 1437-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9333019&dopt=Abstract
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Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts. Author(s): Wollina U. Source: Journal of Cosmetic and Laser Therapy : Official Publication of the European Society for Laser Dermatology. 2003 April; 5(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745597&dopt=Abstract
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Evidence of an association between human papillomavirus and impaired chemotherapy-induced apoptosis in cervical cancer cells. Author(s): Padilla LA, Leung BS, Carson LF. Source: Gynecologic Oncology. 2002 April; 85(1): 59-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925121&dopt=Abstract
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External genital warts: diagnosis, treatment, and prevention. Author(s): Wiley DJ, Douglas J, Beutner K, Cox T, Fife K, Moscicki AB, Fukumoto L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 October 15; 35(Suppl 2): S210-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353208&dopt=Abstract
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Fish oil constituent docosahexa-enoic acid selectively inhibits growth of human papillomavirus immortalized keratinocytes. Author(s): Chen D, Auborn K. Source: Carcinogenesis. 1999 February; 20(2): 249-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10069461&dopt=Abstract
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Generation and genetic characterization of immortal human prostate epithelial cell lines derived from primary cancer specimens. Author(s): Bright RK, Vocke CD, Emmert-Buck MR, Duray PH, Solomon D, Fetsch P, Rhim JS, Linehan WM, Topalian SL. Source: Cancer Research. 1997 March 1; 57(5): 995-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9041206&dopt=Abstract
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Grand challenges in global health and the practical prevention program? Asian focus on cancer prevention in females of the developing world. Author(s): Moore MA, Tajima K, Anh PH, Aydemir G, Basu PS, Bhurgri Y, Chen K, Gajalakshmi V, Hirose K, Jarrahi AM, Ngoan le T, Qiao YL, Shin HR, Sriamporn S, Srivatanakul P, Tokudome S, Yoo KY, Tsuda H. Source: Asian Pac J Cancer Prev. 2003 April-June; 4(2): 153-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875629&dopt=Abstract
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High risk HPV persists after treatment of genital papillomavirus infection but not after treatment of cervical intraepithelial neoplasia. Author(s): Strand A, Wilander E, Zehbe I, Rylander E. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1997 February; 76(2): 140-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9049287&dopt=Abstract
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Human papillomavirus infection and genital warts: update on epidemiology and treatment. Author(s): Stone KM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 April; 20 Suppl 1: S91-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7540876&dopt=Abstract
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Human papillomaviruses and cervical cancer in Bangkok. III. The role of husbands and commercial sex workers. Author(s): Thomas DB, Ray RM, Kuypers J, Kiviat N, Koetsawang A, Ashley RL, Qin Q, Koetsawang S. Source: American Journal of Epidemiology. 2001 April 15; 153(8): 740-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296145&dopt=Abstract
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Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.
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Author(s): Balaram P, Nalinakumari KR, Abraham E, Balan A, Hareendran NK, Bernard HU, Chan SY. Source: International Journal of Cancer. Journal International Du Cancer. 1995 May 16; 61(4): 450-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7759149&dopt=Abstract •
Human vascular smooth muscle cells from restenosis or in-stent stenosis sites demonstrate enhanced responses to p53: implications for brachytherapy and drug treatment for restenosis. Author(s): Scott S, O'Sullivan M, Hafizi S, Shapiro LM, Bennett MR. Source: Circulation Research. 2002 March 8; 90(4): 398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884368&dopt=Abstract
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Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. Author(s): Hawkins DS, Demers GW, Galloway DA. Source: Cancer Research. 1996 February 15; 56(4): 892-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8631030&dopt=Abstract
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Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. Author(s): Vikhanskaya F, Vignati S, Beccaglia P, Ottoboni C, Russo P, D'Incalci M, Broggini M. Source: Experimental Cell Research. 1998 May 25; 241(1): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633517&dopt=Abstract
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Management of anogenital warts (condylomata acuminata). Author(s): von Krogh G. Source: Eur J Dermatol. 2001 November-December; 11(6): 598-603; Quiz 604. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701422&dopt=Abstract
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Management of human papilloma virus vulvo-perineal infection with systemic betainterferon and thymostimulin in HIV-positive patients. Author(s): Frega A, di Renzi F, Stentella P, Pachi A. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1994 March; 44(3): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7909764&dopt=Abstract
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Metal thiolate coordination in the E7 proteins of human papilloma virus 16 and cottontail rabbit papilloma virus as expressed in Escherichia coli. Author(s): Roth EJ, Kurz B, Liang L, Hansen CL, Dameron CT, Winge DR, Smotkin D.
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Source: The Journal of Biological Chemistry. 1992 August 15; 267(23): 16390-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1322900&dopt=Abstract •
Methemoglobin is a supplement for in vitro culture of human nasopharyngeal epithelial cells transformed by human papillomavirus type 16 DNA. Author(s): Wen WN. Source: In Vitro Cellular & Developmental Biology. Animal. 2001 November-December; 37(10): 668-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776972&dopt=Abstract
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N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function. Author(s): Diggle CP, Pitt E, Roberts P, Trejdosiewicz LK, Southgate J. Source: Journal of Lipid Research. 2000 September; 41(9): 1509-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10974058&dopt=Abstract
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New procedure under study may replace Pap smear. Author(s): Solomon R. Source: Posit Living. 2001 April; 10(3): 34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548375&dopt=Abstract
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Noncervical human papillomavirus genital infections. Author(s): Mayeaux EJ Jr, Harper MB, Barksdale W, Pope JB. Source: American Family Physician. 1995 September 15; 52(4): 1137-46, 1149-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668205&dopt=Abstract
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One world, one hope.one gender? Author(s): Gorna R. Source: J Int Assoc Physicians Aids Care. 1996 October; 2(10): 28-30, 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11363910&dopt=Abstract
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Prevalence of human papilloma virus genital infections in sexually transmitted diseases clinic attendees in Ibadan. Author(s): Okesola AO, Fawole OI. Source: West Afr J Med. 2000 July-September; 19(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126083&dopt=Abstract
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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 human papilloma virus; 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 Abnormal Pap Smear Source: Healthnotes, Inc.; www.healthnotes.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Warts Source: Healthnotes, Inc.; www.healthnotes.com
•
Herbs and Supplements Indole-3-carbinol Source: Healthnotes, Inc.; www.healthnotes.com
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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 4. DISSERTATIONS ON HUMAN PAPILLOMA VIRUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to human papilloma virus. 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 “human papilloma virus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on human papilloma virus, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Human Papilloma Virus 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 human papilloma virus. 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: •
An Assessment of College Students' Knowledge and Perception of Risk Regarding Human Papilloma Virus and Related Health Promotion Strategies for Campus Health Personnel by Boyd, Cheryl Atchley, PhD from Ohio University, 1998, 196 pages http://wwwlib.umi.com/dissertations/fullcit/9841644
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 5. PATENTS ON HUMAN PAPILLOMA VIRUS 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.8 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 “human papilloma virus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on human papilloma virus, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Human Papilloma Virus By performing a patent search focusing on human papilloma virus, 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 will tell you how to obtain this information later in the chapter. 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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Human Papilloma Virus
The following is an example of the type of information that you can expect to obtain from a patent search on human papilloma virus: •
Antisense oligonucleotide inhibition of papillomavirus transformed cells Inventor(s): Cowsert; Lex M. (Carlsbad, CA), Crooke; Stanley T. (Carlsbad, CA), Ecker; David J. (Encinitas, CA), Mirabelli; Christopher K. (Dover, MA) Assignee(s): Isis Pharmaceuticals, Inc. (Carlsbad, CA) Patent Number: 5,665,580 Date filed: October 14, 1994 Abstract: Antisense oligonucleotides are taught which hybridize to human papilloma virus transcripts. These oligonucleotides when added to tissue culture cells transformed with human papilloma virus inhibit growth of the transformed cell. Excerpt(s): This invention relates to the inhibition of papillomavirus and the diagnosis and treatment of infections in animals caused by papillomavirus. This invention is also directed to the detection and quantitation of papillomavirus in samples suspected of containing it. Additionally, this invention is directed to oligonucleotides and oligonucleotide analogs which interfere with or modulate the function of messenger RNA from papillomavirus. Such interference can be employed as a means of diagnosis and treatment of papillomavirus infections. It can also form the basis for research reagents and for kits both for research and for diagnosis. The papillomaviruses (PV) are widespread in nature and are generally associated with benign epithelial and fibroepithelial lesions commonly referred to as warts. They have been detected in and isolated from a variety of higher vertebrates including human, cattle, rabbits, deer and several avian species. Although these viruses are generally associated with benign lesions, a specific subset of the viruses have been associated with lesions that may progress to carcinomas. The implication that these viruses may play an etiologic role in the development of some human cancers follows from numerous studies that have shown the presence of transcriptionally active human papillomavirus (HPV) deoxyribonucleic acids in a high percentage of certain cancerous lesions. Zur Hausen, H. and Schneider, A. 1987. In: The Papovaviridae, vol. 2, edited by N. P. Salzman and P. M. Howley, pp. 245-264. Plenum Press, New York. In man, human papillomaviruses cause a variety of disease including common warts of the hands and feet, laryngeal warts and genital warts. More than 57 types of HPV have been identified so far. Each HPV type has a preferred anatomical site of infection; each virus can generally be associated with a specific lesion. Genital warts, also referred to as venereal warts and condylomata acuminata, are one of the most serious manifestations of PV infection. As reported by the Center for Disease Control, the sexual mode of transmission of genital warts is well established and the incidence of genital warts is on the increase. The seriousness of genital warts is underlined by the recent discovery that HPV DNA can be found in all grades of cervical intraepithelial neoplasia (CIN I-III) and that a specific subset of HPV types can be found in carcinoma in situ of the cervix. Consequently, women with genital warts, containing specific HPV types are now considered at high risk for the development of cervical cancer. Current treatments for genital warts are inadequate. Web site: http://www.delphion.com/details?pn=US05665580__
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Attenuated microorganism strains expressing HPV proteins Inventor(s): Haefliger; Denise Nardelli (Lausanne, CH), Kraehenbuhl; Jean-Pierre (Rivaz, CH) Assignee(s): BTG International Limited (London, GB) Patent Number: 6,458,368 Date filed: April 9, 1999 Abstract: Attenuated strain of a prokaryotic microorganism, being an attenuated strain of Salmonella suitable for use in a live vaccine for administration to a human or animal, in which the microorganism is transformed with nucleic acid encoding Human papilloma virus 16 L1 major capsid protein. The protein assembles in the microorganism to form virus-like particles (VLPs) that are capable of illiciting an immune response sufficient to produce neutralizing antibodies in serum and genital secretions specific for Human papilloma 16 infection when the microorganism is administered to the human or animal body. Excerpt(s): The present invention relates to attenuated strains of prokaryotic microorganisms, in particular Salmonella, transformed with nucleic acid encoding papillomavirus virus proteins, to compositions comprising these microorganisms, especially for use as vaccines, and to the medical uses of these strains. In a further aspect, the present invention provides a method of producing assembled papillomavirus virus like particles (VLPs). Human papilloma virus (HPV) 16 is the major type of HPV which, in association with cofactors, can lead to cervical cancer (49). Studies on HPV have been hampered by the inability to propagate the virus in culture, the lack of animal models and the paucity of virions in clinical lesions. This has led to the development of alternative approaches of antigen production for immunological studies. The conformational dependency of neutralizing epitopes, as observed in experimental animal papillomavirus systems (8, 22) suggests that properly assembled HPV particles are critical for the induction and detection of clinically relevant immune reactivity. The HPV capsids are formed by 72 pentameric capsomers of L1 proteins arranged on a T7 icosahedral lattice (15). Recently, a number of investigators have demonstrated the production of HPV capsids, i.e. virus like particles (VLP), by utilizing baculovirus, vaccinia virus or yeast expression systems (15, 22, 45, 48, 61). The potential of VLPs as subunit vaccines has been demonstrated using the cottontail rabbit papillomavirus (CRPV) (4), the canine oral papillomavirus (COPV) (57), and the HPVll models (45). Web site: http://www.delphion.com/details?pn=US06458368__
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Cervical specimen self-sampling device Inventor(s): Fournier; Arthur M. (Miami, FL) Assignee(s): Bay Point Group, Inc. (Miami, FL) Patent Number: 6,475,165 Date filed: November 20, 2000 Abstract: A human female cervical specimen gathering device is disclosed which can be self administered by women. This device is an improvement over conventional cervical tissue sampling, which requires a speculum examination, and prior self-sampling devices, which are not compatible with thin-prep cytology easily adaptable to existing
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pap-smear technology, for thin smear cytology (automated or manual) microbial cultures and assays such as polymer-chain-reaction assays for human papilloma virus. 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 can 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 in women from cervical cancer. Prior to the pap test, cervical cancer was the most common cause of cancer deaths in women. In countries where pap smears are 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 (HPV), 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=US06475165__ •
Diagnosis of dysplasia using laser induced fluoroescence Inventor(s): Mahadevan; Anita (Austin, TX), Mitchell; Michele F. (Houston, TX), Ramanujam; Nirmala (Austin, TX), Richards-Kortum; Rebecca R. (Austin, TX), Thomsen; Sharon (Houston, TX) Assignee(s): Board of Regents, The University of Texas System (Austin, TX) Patent Number: 5,421,339 Date filed: May 12, 1993 Abstract: Apparatus and in vivo methods to distinguish normal and abnormal cervical tissue and to detect cervical intraepithelial neoplasia (CIN) in a diagnostic cervical tissue sample. Induced fluorescence intensity spectra from known normal cervical tissue and a diagnostic tissue sample are obtained from the same patient. Peak fluorescence intensity values for normal tissue samples are averaged, as are slope measurements from
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predetermined portions of spectra induced in both known normal cervical tissue and the diagnostic tissue sample. Peak fluorescence intensities of diagnostic tissue spectra are divided by average peak fluorescence intensity values for normal tissue in the same patient to yield relative peak fluorescence intensity values. Normal and abnormal cervical tissues are distinguished using a predetermined empirical discriminant function of slope measurements derived from normal tissue spectra and relative peak fluorescence intensity measurements in the same patient. CIN is distinguished from tissue with human papilloma virus injection or inflammation using a predetermined empirical discriminant function of average slope measurements on spectra from known normal tissue and slope measurements on a diagnostic tissue spectrum. Excerpt(s): The invention relates to methods and apparatus to differentiate between histologically normal and histologically abnormal tissues, and to differentiate neoplastic tissue from histologically abnormal non-neoplastic tissue. Although there has been a significant decline in the incidence and mortality of invasive cervical carcinoma over the last 50 years, there has been an increase in both the reported and actual incidence of CIN. As a result, it has been estimated that the mortality of cervical carcinoma may rise by 20% in the years 2000-2004 unless screening techniques for CIN are improved. Present screening for CIN and cervical cancer is relatively inexpensive but labor intensive because it initially relies on the results of a Pap smear; a false negative error rate of 20-30% is associated with insufficient cell sampling and/or inexpert reading of Pap smears. Given an abnormal Pap smear, colposcopic examination of the cervix (with a magnifying lens) followed by colposcopically directed biopsy and histologic examination of the tissue sample can provide a diagnosis of CIN. Histologic confirmation of the diagnosis, while relatively time-consuming and expensive, is necessary because the accuracy of classification among abnormal tissues by colposcopy alone is limited, even in experienced hands. Web site: http://www.delphion.com/details?pn=US05421339__ •
Diagnostic peptides of human papilloma virus Inventor(s): Palefsky; Joel M. (Redwood City, CA), Schoolnik; Gary K. (Palo Alto, CA) Assignee(s): The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) Patent Number: 4,777,239 Date filed: July 10, 1986 Abstract: A series of seventeen synthetic peptides which are capable of raising antibodies specific for certain desired human papilloma virus (HPV) are useful in diagnosis and therapy of conditions associated with HPV infection. Excerpt(s): The invention relates to vaccines and diagnostics relevant to human papilloma virus (HPV) infection. In particular, synthetic peptides corresponding to regions of putative peptides for types of HPV which infect the genital region raise antibodies useful in diagnosis and in protection against infection. Human papilloma virus appears to be associated with the development of cervical carcinoma, a malignant condition which appears to be preceded by several stages of cervical intraepithelial neoplasia (CIN). The association of HPV infection with CIN has long been recognized (Meiseles, A., et al, Gynecol Oncol (1981) 12: 3111-3123; Crum, C. P., et al, ibid (1983) 15: 88-94; Syrjanen, K. J., Obstet Gynecol Surv (1984) 39: 252-265). In fact, IgG reactive with a group-specific papilloma virus antigen was detected in 93% of women with cervical
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carcinoma and 60% of those with CIN, but not in any control subjects (Baird, P. J., Lancet (1983) ii: 17-18), and the presence of HPV DNA in these lesions has been recognized by several groups. There are approximately forty different types of HPV, which are classified by DNA sequence homology using hybridization techniques. Samples having more than 50% homology, as judged by hybridization, are placed into the same type designation. The various types appear to be rather tissue specific. HPV-6, HPV-11, HPV16, HPV-18, and HPV-31 appear to be associated with the genital tract; others appear to be associated with warts or epidermal dysplasias in other tissues. However, HPV-6 and HPV-11 are associated with condyloma type lesions, while HPV-16, HPV-18 and HPV31 are associated with cervical intraepithelial neoplasia, including invasive carcinoma. Web site: http://www.delphion.com/details?pn=US04777239__ •
Enhancement of cancer cell death Inventor(s): Lau; Allan S. (San Francisco, CA), Yeung; Michael C. (San Francisco, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,976,800 Date filed: June 27, 1997 Abstract: The invention provides for methods and compositions based on the expression of cellular levels of double-stranded RNA dependent kinase (PKR), an interferonregulated gene, is used to enhance cancer cell death. The PKR gene is encoded by vectors, optionally containing specific promoters that are activated only in specific target cells. Cells producing PKR are treated with non-toxic, low doses of apoptosis-inducing agents, such as TNF-.alpha. or poly I:C, leading to programmed cell death without the use of conventional chemotherapeutic agents. Designing of recombinant viral vectors for gene therapy based on these expression systems for the treatment of human hepatitis B and C viruses, human papilloma virus, and other cancers and viral diseases is also taught. Excerpt(s): The invention relates to methods and compositions for cancer treatment using vectors expressing serine/threonine protein kinases that are activated by doublestranded RNA to enhance the sensitivity of neoplastic cells to immunomodulators and chemotherapeutic agents. Cancer therapy, especially a type of therapy that can be applied to different types of cancers, remains a goal of medicine. A number of different treatments have been used with varying degrees of success. In general, treatment of cancer includes surgical resection, x-ray irradiation, radioisotope treatment, conventional chemotherapy, or specific combinations of these types of treatments. These methods have inherent limitations, however. For example, surgical resection, while targeted at grossly identifiable tumor mass, is limited in scope and cannot eliminate microscopic, metastatic tumor cells. Irradiation and radioisotope therapy, by contrast, are potent and effective for microscopic cancer cells, but can induce extensive damage of normal tissues which may result in permanent fibrosis and scarring. Similarly, conventional chemotherapy often causes tumor cell death by directly intoxicating both normal and malignant cells. The non-specific nature of the cytotoxicity resulting from these treatments poses significant problems for the patient, including massive tissue necrosis, potential kidney damage due to renal overload by metabolic waste such as uric acids, bone marrow failure, and gastrointestinal mucosal sloughing and bleeding. One of the major obstacles in this area is to develop a treatment regime that works despite the multiple pathways that contribute to cancer cell and tumor growth. A number of genes have been implicated in the transformation of normal cells to neoplastic cells, and
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cancer cell growth and proliferation. Often, multi-activation of cancer cells thwarts effective treatment. Web site: http://www.delphion.com/details?pn=US05976800__ •
Formulations containing hyaluronic acid Inventor(s): Asculai; Samuel Simon (Toronto, CA), Falk; Rudolf Edgar (Toronto, CA), Harper; David W. (Oakville, CA), Hochman; David (Thornhill, CA), Klein; Ehud Shmuel (Givat Savyon, IL), Purschke; Don (Toronto, CA) Assignee(s): Hyal Pharmaceutical Corp. (CA) Patent Number: 6,114,314 Date filed: December 1, 1994 Abstract: Topically applied transdermally quick penetrating (best targeting the epidermis and subsequently remaining there for a prolonged period of time) systemic independent acting, combinations and formulations which employ, combine, or incorporate a therapeutically effective non-toxic (to the patient) amount of a drug which inhibits prostaglandin synthesis together with an amount of hyaluronic acid and/or salts thereof (for example the sodium salt) and/or homologues, analogues, derivatives, complexes, esters, fragments, and/or sub units of hyaluronic acid to treat a disease and condition of the skin and exposed tissue for example, basal cell carcinoma, the precancerous, often recurrent, actinic keratoses lesions, fungal lesions, "liver" spots and like lesions (found for the most part in the epidermis), squamous cell tumours, metastatic cancer of the breast to the skin, primary and metastatic melanoma in the skin, genital warts cervical cancer, and HPV (Human Papilloma Virus) including HPV of the cervix, psoriasis (both plaque-type psoriasis and nail bed psoriasis), corns on the feet and hair loss on the head of pregnant women and remain in the skin for a prolonged period of time. Excerpt(s): This invention also relates to formulations suitable for use in such treatments, the use of such formulations in such treatments, methods of such treatment, and the delivery of drugs for such treatments. Basal cell carcinoma is presently treated by surgery. Each lesion, together with all surrounding and underlying tissue (dermis, epidermis, and subdermis), is cut out. In some instances, surgery, while necessary for the patient's welfare, may put the patient at risk in some other respect (for example, a lesion on a patient's temple whose removal (resection) may jeopardize the patient's health). Squamous cell tumours are also treated the same way as are other forms of cancer in the skin and exposed tissue. Furthermore, other conditions and diseases of the skin and exposed tissue are treated the same way or in ways that cause discomfort to the patient, for example melanoma, genital warts, cervical cancer, HPV (Human Papilloma Virus). Actinic keratoses lesion is dealt with similarly. Additionally, liquid nitrogen has been used to remove the lesion. Web site: http://www.delphion.com/details?pn=US06114314__
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High throughput papilloma virus in vitro infectivity assay Inventor(s): Hall; Kathleen S. (273B Orion Way, Stateline, NV 89449), Smith; Lloyd H. (1309 Aspen Pl., Davis, CA 95616) Assignee(s): none reported Patent Number: 6,218,105 Date filed: January 7, 2000 Abstract: A high throughput virus in vitro infectivity assay method comprising growing cells in a multi-well format, infecting the cells with intact virion incubated with a test agent, and measuring expression of at least one viral nucleic acid sequence in the cells. The method also preferably comprises incubating intact virion without test agent to define a control. The cells are preferably human keratinocyte cells grown in monolayers. The viral nucleic acid sequence will generally comprise viral mRNA. In one preferred embodiment, the intact virion comprise Human Papilloma Virus, and more preferably Human Papilloma Virus-11. Measuring expression is generally carried out by releasing the viral mRNA from the cells by lysis, amplifying the mRNA as CDNA via RT-PCR, and detecting amplicons with specific probes. Cell lysis may be carried out by heating or by treatment with detergent. Excerpt(s): This invention relates to a high-throughput in vitro method of testing antiviral activity of various agents. More specifically, it describes a method of testing effectiveness of anti-papilloma virus agents which act early in the infection process. The method is useful in testing effectiveness of existing and potential antiviral drugs, including the efficacy of vaccines, in particular, future drugs directed to treatment of human papilloma virus infections. Cervical cancer is strongly linked to human papilloma virus (HPV) infection. HPV types 6 and 11 are associated with condylomata and low grade dysplasia while HPV-16 and -18 are associated with high grade dysplasia and cervical cancer. Information on the human immune response against Human papilloma viruses (HPV) predominantly comes from serological studies that used enzyme-linked immunosorbent assays (ELISA) targeted against HPV antigens. The simple detection of anti-HPV antibodies, however, fails to identify neutralizing antibodies (N-Abs) against HPV. Thus it has been widely recognized that only the detection of specific N-Abs against HPV will identify an effective immune response (protective antibodies). See, e.g., Foster et al., Papillomavirus Report 8,127-131 (1997). Testing of the antiviral effectiveness of the new and existing agents against human papillomavirus are still performed in the in vivo testing involving use of laboratory animals and human subjects. These studies are expensive, time consuming and altered by individual differences among subjects. Web site: http://www.delphion.com/details?pn=US06218105__
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Human papilloma virus anti-sense oligonucleotides Inventor(s): Alvarez-Salas; Luis (Bethesda, MD), DiPaolo; Joseph (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 6,084,090 Date filed: September 5, 1997
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Abstract: Antisense oligonucleotides having phosphorothioate backbone structure and sequences complementary to nucleotides contained with residues 415 to 445 of human papilloma virus 16 (HPV-16) are disclosed. Methods of treatment using antisense oligonucleotides having phosphorothioate backbone structure and nucleotide sequences complementary to nucleotides contained with residues 415 to 445 of HPV-16 are disclosed. Excerpt(s): The present invention relates to the use of antisense oligonicleotides to inhibit a Human Papilloma virus (HPV), and specifically relates to use of antisense oligonucleotides specific for nucleotides 415 to 445 of the DNA sequence of HPV-16. Papilloma viruses are small DNA viruses that induce the hyperproliferation of epithelial cells. Approximately 70 different genotypes of human papilloma virus (HPV) have been isolated. Some HPV genotypes (e.g., 1, 2 4, and 7) have been associated with human benign squamous papillomas (warts and condylomas) and others (e.g., 16 and 18) have been associated with human neoplastic and preneoplastic lesions (DiPaolo, et al., 1993, Crit. Rev. Oncogen. 4:337-360). Surgery is commonly used for treatment of high-grade lesions due to the lack of effective alternatives. Cervical laser ablation therapy, however, does not in the long term influence the natural history of cervical human papillomavirus-associated diseases in women. Interferons have not proved an effective antiviral or anticancer treatment. Chemotherapy (e.g., cisplatin, alone or combined with other chemotherapy agents such as 5FU) has generally not proved to be effective in treatment of many cervical cancers. Moreover, most chemotherapeutic agents are cytotoxic, leading to toxic side effects and the development of multiple drug resistance. Therefore, there is a need for reagents than can specifically inhibit the growth of HPV-associated tumor cells, while avoiding serious toxic reactions. Web site: http://www.delphion.com/details?pn=US06084090__ •
Human Papilloma Virus detection in a nucleic acid amplification process using general primers Inventor(s): Meijer; Christophorus Joannes (Leiden, NL), Snijders; Petrus Josephus (Amstelveen, NL), van den Brule; Adrianus Johannes ('s-Hertogenbosch, NL), Walboomers; Jan Marcus (Amsterdam, NL) Assignee(s): Stichting Researchfonds Pathologie (Amsterdam, NL) Patent Number: 6,352,825 Date filed: November 25, 1996 Abstract: The oligonucleotides: (i) the 23-mer 5'-TTTGTTACTGTGGTAGATACTAC-3' (SEQ ID NO: 1) or the 23-mer which is complementary to it; (ii) a 23-mer derived from (i) by from 1 to 5 nucleotide substitutions; (iii) a 23.sup.+ -mer having a 3' terminal sequence consisting of (i) or (ii); (iv) a fragment of (i) or (ii) having a length of from 8 to 18 nucleotides; (v) the 25-mer 5'-GAAAAATAAACTGTAAATCATATTC-3' (SEQ ID NO: 2) or the 25-mer which is complementary to it; (vi) a 25-mer derived from (v) by from 1 to 5 nucleotide substitutions; (vii) a 25.sup.+ -mer having a 3' terminal sequence consisting of (v) or (vi); (viii) the 28-mer 5'GAAAAATAAACTGTAAATCATATTCTTC-3' (SEQ ID NO: 10) or the 28-mer which is complementary to it; (ix) the 28-mer 5'-GAAAAATAAACTGTAAATCATATTCCTC-3' (SEQ ID NO: 18) or the 28-mer which is complementary to it; (x) a 28-mer derived from (viii) or (ix) by from 1 to 5 nucleotide substitutions; (xi) a 28.sup.+ -mer having a 3' terminal sequence consisting of (viii), (ix) or (x); (xii) a fragment of (v), (vi), (vii), (ix) or (x) having a length of from 8 to 18 nucleotides, useful as a primer in a nuc acid
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amplification process, e.g. a general primer PCR or NASBA, or LCR, to amplify DNA of genital HPV genotypes, e.g. in a method of analyzing a sample for the presence therein of HPV. Excerpt(s): The invention is in the field of sample analysis to determine the presence therein of Human Papilloma Virus (HPV) genotypes by amplifying HPV DNA present in the sample with a nucleic acid amplification process, e.g. the Polymerase Chain Reaction (PCR), using general primers (GPs). More in particular, the invention relates to an analysis of cervical smears which allows cervical carcinoma-related diagnosis and prognosis wherein the analysis comprises a GP-nucleic acid amplification process, e.g. GP-PCR, to determine whether the sample contains any HPV, followed by a typing of the HPV genotype present. The PCR method has been introduced as the most sensitive method for the detection of HPV DNA in clinical specimens. However, a significant heterogeneity at the nucleotide level is found between the different HPV genotypes. This has hampered the development of a simple universal PCR test for the detection of all HPV genotypes. Despite this, HPV-PCR methods have been developed which allow the detection of a broad spectrum of mainly mucosotropic HPV genotypes (Manos et al., 1989; Gregoire et al., 1989; Snijders et al., 1990). A combination of the general primers GP5 and GP6, originally selected from the HPV L1 region on the basis of sequence information of HPV6, HPV11, HPV16, HPV18, HPV31 and HPV33 (Snijders et al., 1990; WO 91/10675), was found to amplify target DNA of at least 27 mucosotropic HPV genotypes under conditions that allow mismatch acceptance (Van den Brule et al., 1990a, 1992; de Roda Husman et al., 1994a). The strength of this GP5/6-mediated PCR method has been substantiated further by the detection of HPV DNA in 100% of cervical scrapes classified cytomorphologically as Pap IV (carcinoma in situ) and Pap V (carcinoma) in the Netherlands (Van den Brule et al., 1991; de Roda Husman et al., 1994a). This suggests that in the Dutch population all genital high risk HPVs can be detected by this assay. Web site: http://www.delphion.com/details?pn=US06352825__ •
Human papilloma virus genes and their use in gene therapy Inventor(s): Schlegel; Richard (Rockville, MD) Assignee(s): Georgetown University () Patent Number: 5,576,206 Date filed: May 20, 1994 Abstract: A process of immortalizing cells with isolated HPV-16, 18, 31, 33 or 35 E6 and E7 genes or the E7 gene alone to produce non-tumorigenic immortalized cell lines which retain the differentiated phenotypic characteristics of the parent cells. Excerpt(s): The present invention is directed to the immortalizing E6 and E7 genes of human papilloma viruses, such as virus types 16, 18, 31, 33 and 35 and transfection of these genes into target cells. In vivo expression of E6/E7 genes immortalizes the target cell which retains its phenotypic characteristics. More than 50 different types of human papillomariruses (HPVs) have now been isolated from a variety of squamous epithelial lesions, and approximately 18 of them have been associated with anogenital tract lesions. Some of these, such as HPV type 6 (HPV-5) and HPV-11, are generally associated with benign proliferative lesions, including condyloma acuminata, which only infrequently progress to cancers. Others, such as HPV-16, HPV-18, HPV-31, HPV33, and HPV-35, are associated with genital tract lesions, which are at risk for malignant
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progression, and with genital tract cancers (1). The E7 ORF of HPV-16 encodes a 21kilodalton phosphoprotein (14), and the E7 genes of HPV-16 and HPV-18 are sufficient for focus formation of established rodent fibroblasts such as NIH 3T3 cells (15, 16, 17, 18, 19). The E7 protein is functionally and structurally related to the adenovirus E1A proteins (AdE1A); it can transactivate the AdE2 promoter and can cooperate with an activated ras oncogene to transform primary rat cells (16, 20). The amino-terminal 38 amino acids of E7 are strikingly similar to portions of conserved domain 1 (amino acids 37 to 49) and domain 2 (amino acids 116 to 137) of the AdE1A proteins (16) as well as to portions of the large tumor antigens (T) of papovaviruses. The AdE1A, simian virus 40 (SV40) T, and HPV-16 E7 proteins form specific complexes with the product of the retinoblastoma tumor suppressor gene (p105-RB) (21, 22, 23), and complex formation with p105-RB is mediated through these conserved sequences for AdE1A and SV40 T (21, 22) as well as for HPV-16 E7. The transforming potential of the E6 gene has been less well defined. In NIH 3T3 fibroblasts, it may contribute to characteristics of the transformed phenotype such as anchorage independence (25) or tumorigenicity in nude mice (26). In human cells, E6 appears to cooperate with the E7 oncopprotein in mediating-cellular immortalization. Recently, it has been demonstrated that E6 binds to, and mediates the degradation of, the cellular tumor suppressor protein p53. It has been shown recently that both the E6 and E7 RFs are necessary for the extension of the life span of human diploid fibroblasts (34). Mutation studies of the early HPV-16 genes that directly participate in the in vitro transformation of primary human keratinocytes has shown that both the full-length E6 and E7 genes are required for induction of keratinocyte immortalization and resistance to terminal differentiation (35). Keratinocyte transformation with HPV-18 DNA requires only the HPV-18 regulatory region and the E6/E7 genes which induce two progressive steps in cellular transformation (36). Web site: http://www.delphion.com/details?pn=US05576206__ •
Human papilloma virus inhibition by a hairpin ribozyme Inventor(s): DiPaolo; Joseph (Bethesda, MD), Galasinski; Scott C. (Rockford, IL), Hampel; Arnold (DeKalb, IL), Siwkowski; Andrew M. (Sycamore, IL) Assignee(s): Northern Illinois University (DeKalb, IL), United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 5,683,902 Date filed: March 21, 1995 Abstract: Synthetic catalytic RNAs, i.e. ribozyme, including a hairpin portion, binding sites for binding to a human papilloma virus after viral base 419 and 434, respectively, and cleavage sites for cleaving the virus at the binding sites have been constructed. Excerpt(s): The present invention relates to an RNA catalyst, i.e. ribozyme, which cleaves Human Papilloma virus into a fragment having a 5' hydroxyl and a fragment having a 2',3' cyclic phosphate. The products of the reaction described herein resemble those resulting from the natural hydrolysis of RNA. In the United States, cervical cancer affects approximately 8.6 women per 100,000 each year. In woman, HPV-16 is frequently associated with latent infections, benign and premalignant cervical lesions (dysplasias/CIN) and half of invasive cervical carcinomas. In males, HPV-16 is associated with subclinical macular or clinical papular lesions. Bowenoid papulosis of the penis resembles carcinoma in situ. Cervical cancer, which kills at least 500,000 women worldwide each year, proceeds through progressive cellular changes from
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benign condylomata to high-grade dysplasias/CIN before developing into an invasive cancer. Over five billion health care dollars are spent in the United States each year on the detection and treatment of these lesions. The current policy in genitourinary clinics is surgery for high-grade lesions due to the lack of superior alternatives. Cervical laser ablation therapy does not in the long term influence the natural history of cervical human papillomavirus-associated diseases in women. Interferons, per se, have been disappointing insofar as acute viral infection is concerned, usually because treatment cannot be started in time. Therefore, it has been assumed that any benefit with interferons is due to anti-proliferative effect and not due to antiviral. Web site: http://www.delphion.com/details?pn=US05683902__ •
Human papilloma virus type 57 and the DNA thereof Inventor(s): de Villiers; Ethel-Michele (Hirschberg, DE), Hausen; Harald zur (Heidelberg, DE), Hirsch-Behnam; Anja (Heidelberg, DE) Assignee(s): Behringwerke Aktiengesellschaft (Marburg, DE) Patent Number: 5,187,090 Date filed: August 4, 1989 Abstract: The invention describes the isolation for the first time of human papilloma virus (HPV) 57, the partial characterization of its genome and its cloning in pUC 19. This opens up a way of diagnosing those tumors (oral, genital and cutaneous tumors) which are associated with HPV 57. Excerpt(s): The human papilloma viruses (HPV) form a group of more than 50 different types. HPV has been found associated with benign (warts, condylomas in the genital region) and malignant (carcinomas of the skin and the vagina) epithelial neoplasms. Papilloma viruses cannot be grown in culture. Thus, methods of genetic manipulation are required for the use of human papilloma virus type 57 DNA (HPV 57 DNA) as a diagnostic aid and for obtaining the expression products, for using them as antigens, for isolating antibodies and for preparing corresponding diagnostic aids and therapeutic agents. The invention is based on the isolation for the first time of HPV 57, partial characterization of its genome and cloning in pUC 19. This opens up a way of diagnosing tumors (oral, genital and cutaneous tumors) associated with HPV 57. The invention is defined in the patent claims. Further embodiments of the invention are described in detail hereinafter. Web site: http://www.delphion.com/details?pn=US05187090__
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Human papilloma virus vaccine with disassembled and reassembled virus-like particles Inventor(s): Mach; Henryk (Ambler, PA), Shi; Li (Eagleville, PA), Volkin; David B. (Doylestown, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,245,568 Date filed: March 13, 2000 Abstract: Human Papillomavirus vaccine formulations which contain virus-like particles (VLPs) can be made more stable and have an enhanced shelf-life, by treating the VLPs to
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a disassembly and reassembly process. Also provided are formulation buffers to long term stable storage of VLPs. Excerpt(s): This invention relates to a human papillomavirus (HPV) vaccine which contains virus-like particles (VLPs) which have been disassembled into capsomeres and then reassembled into VLPs. This invention also relates to processes of making this vaccine resulting in more homogeneous HPV VLPs and greatly improved storage stability. Human Papillomavirus (HPV) infects the genital tract and has been associated with various dysplasias, cancers, and other diseases. These diseases are currently targets for vaccine development and vaccines containing virus-like particles (VLPs) which contain L1 or the combination of L1+L2 proteins are currently in clinical trials. It has been found, however, that recombinant L1 protein HPV VLPs purified from yeast are not stable during long-term storage, either in solution or when adsorbed onto aluminum adjuvant particles. Web site: http://www.delphion.com/details?pn=US06245568__ •
Human papilloma virus vectors Inventor(s): Apt; Doris (Sunnyvale, CA), Khavari; Paul (Stanford, CA), Stemmer; William P. C (Los Gatos, CA) Assignee(s): Maxygen, Inc. (Redwood City, CA) Patent Number: 6,399,383 Date filed: October 27, 1998 Abstract: The invention provides human papillomavirus vectors useful in gene therapy. Such a vector contains E1 and E2 coding regions from a benign or low-risk human papillomavirus operably linked to a promoter and enhancer, and an LCR region from a human papillomavirus comprising an origin of replication including binding sites for the E1 and E2 proteins. The invention further provides methods of using such vectors in gene therapy, methods of controlling expression using a patch, and methods of using such vectors to evolve drugs for stimulation of hair growth or alteration of hair color. Excerpt(s): The invention resides in the technical fields of virology and molecular genetics. Papillomaviruses are small, nonenveloped, icosahedral DNA viruses that replicate in the nucleus of squamous epithelial cells. Papillomaviruses consist of a single molecule of double-stranded circular DNA about 8,000 base pairs (bp) in size within a spherical protein coat of 72 capsomeres. Such papillomaviruses are classified by the species they infect (e.g., bovine, human, rabbit) and by type within species. Over 50 distinct human papillomaviruses ("HPV") have been described. See, e.g., Fields Virology (3rd ed., eds. Fields et al., Lippincott-Raven, Philadelphia, 1996). The DNA of many papillomaviruses, including over 50 human viruses, has been cloned and sequenced. Although there is a high degree of sequence divergence between species, all papillomaviruses share some common features of genome organization. That is, the genome is subdivided into an early region containing proteins E1-E8 (not all are present in all species), a late region, containing genes L1 and L2, and a long control region (LCR) of transcription, including the promoter and enhancer for the viral early genes and the origin of replication. The early region encodes genes required for viral DNA replication, cellular proliferation, and, in some viruses, cellular transformation. The E1 gene and E2 gene encode E1 and E2 polypeptides that bind to the LCR region and induce replication from the origin of replication in the LCR region. The E5, E6 and E7 proteins of the different papillomaviruses have proliferation and sometimes transforming activities.
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The late region (about 3 kb) codes for the capsid proteins. L1 is the major capsid protein and is relatively well conserved among all the papillomavirus types. The L1 proteins is about 500 amino acids in size. L1 probably induces the major humoral and cell-mediated responses to viral infection. The L2 proteins are about 500 amino acids in size, account for only a small proportion of the virion mass, and their function is not yet clear. The LCR region contains an origin of replication with binding sites for E1 and E2 and other cis acting sequences in the promoter and enhancer region. Web site: http://www.delphion.com/details?pn=US06399383__ •
Human papillomavirus vaccine formulations Inventor(s): Shi; Li (Eagleville, PA), Volkin; David B. (Doylestown, PA), Mach; Henryk (Ambler, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,251,678 Date filed: February 2, 2000 Abstract: New human papilloma virus (HPV) vaccine formulations exhibit enhanced long-term stability. Formulation components can include: virus-like particles (VLPs) absorbed onto aluminum, a salt, non-ionic surfactant, and a buffer. Additional formulations also contain a polymeric polyanionic stabilizer and a salt either in the presence or absence buffering agents and nonionic detergent. Excerpt(s): This invention related to human papillomavirus (HPV) vaccine formulations which provide enhanced long-term storage stability. Human Papillomavirus (HPV) infects the genital tract and has been associated with various dysplasias, cancers, and other diseases. These diseases are currently targets for vaccine development and vaccines containing virus-like particles (VLPs) which contain L1 or the combination of L1+L2 proteins are currently in clinical trials. It has been found, however, that HPV VLPs are not stable during long-term storage, either in solution or when absorbed onto aluminum adjuvant particles. Web site: http://www.delphion.com/details?pn=US06251678__
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Method for protein expression Inventor(s): Edwards; Stirling John (Northcote, AU), Webb; Elizabeth Ann (Eltham, AU) Assignee(s): CSL Limited (Victoria, AU) Patent Number: 6,303,128 Date filed: July 23, 1999 Abstract: A vector system for expressing foreign proteins or polypeptides in bacteria such as E. coli is disclosed. The vector system is especially useful in obtaining expression of non-transforming variants of human papilloma virus antigens. Excerpt(s): This invention relates to an improved method for protein expression, particularly in bacteria such as Escherichia coli. In particular, this invention relates to an improved expression vector system and to the use of this system to obtain expression of foreign proteins or polypeptides in bacteria such as E. coli. By way of example, the improved expression vector system may be used to obtain expression of non-
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transforming variants of human papilloma virus (HPV) antigens as disclosed in detail in International Patent Application No. PCT/AU95/00868. In International Patent Application No. PCT/AU88/00164, it is disclosed that a fusion protein having a foreign protein or polypeptide component fused to the enzyme glutathione-S-transferase (GST), (E.C. 2.5.1.18), preferably to the carboxy-terminal of the enzyme, avoids several of the difficulties associated with known fusion proteins, for instance fusions wherein the foreign protein or polypeptide is expressed as a fusion with E. coli.beta.-galactosidase, in that the GST fusion proteins are generally soluble and can be purified from bacterial lysates under non-denaturing conditions, for example by affinity chromatography on a column of immobilised glutathione. The GST enzyme in the fusion protein may be derived from the parasite helminth Schistosoma japonicum, or it may be derived from other species including humans and other mammals. The GST fusion proteins disclosed in International Patent Application No. PCT/AU88/00164 may be used as such, since the foreign protein or polypeptide component thereof often retains its antigenicity and functional activity. Alternatively, the fusion protein may be cleaved to provide the foreign protein or polypeptide as a synthesis product, and when the production of such a synthetic protein or polypeptide is desired a cleavable link may be provided in the fusion protein between the glutathione-S-transferase component and the foreign protein or polypeptide component. The cleavable link is preferably one which can be cleaved by a site-specific protease such as thrombin, blood coagulation Factor Xa, or the like. Web site: http://www.delphion.com/details?pn=US06303128__ •
Method for treating infectious viral diseases Inventor(s): Kronis; K. Anne (Tampa, FL), Lezdey; Darren (Indian Rocks Beach, FL), Lezdey; John (Indian Rocks Beach, FL) Assignee(s): AlphaMed Pharmaceutical Corp. (Clearwater, FL) Patent Number: 6,468,557 Date filed: January 5, 2001 Abstract: The present invention provides for the treatment of an individual suffering from infections from herpes virus or human papilloma virus by utilizing a cromolyn compound. The treatment includes the use of a corticosteroid or L-lysine that can be administered separately or in combination. Excerpt(s): The present invention relates to the treatment of infectious viral diseases. More particularly, there is provided the treatment of viral infections caused by herpes simplex virus (HSV) or human papilloma virus (HPV) with a cromolyn compound. There are two immunologic types of herpes simplex virus (HSV), HSV-1 and HSV-2. HSV-1 commonly causes herpes labialis and keratitis. HSV-2, usually genital, is transmitted primarily by direct contact with lesions, most often venereally, and also produces skin lesions. Shingles is believed to be a result of HSV infection. Web site: http://www.delphion.com/details?pn=US06468557__
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Method, reagent and kit for genotyping human papilloma virus Inventor(s): Chong; Sylvia (Hamilton, CA), Kierstead; Timothy (Phoenixville, PA), Mahony; James (Oakville, CA), Seadler; Alan (Export, PA) Assignee(s): Visible Genetics Inc. (Toronto, CA) Patent Number: 6,503,704 Date filed: June 25, 2001 Abstract: The present invention is directed to a method of determining the genotype of a human papilomavirus in a sample by amplifying a portion of the L1 open reading frame of human papilomavirus genome with the amplification primer having SEQ ID NO:2, the sequencing primer having SEQ ID NO:3 and an additional sequencing primer specific to HPV51 having SEQ ID NO:5. Excerpt(s): This application relates to a method, reagent and kit for genotyping of human papillomavirus, and in particular to the sequencing of human papillomavirus for determination of viral type. Cancer of the cervix is one of the most common malignancies in women around the world. Over 90% of both invasive cervical cancer lesions and precursor lesions are associated with the presence of human papillomavirus (HPV), and many epidemiological studies have established that HPV infection is the major risk factor for squamous intraepithelial lesions and cervical carcinoma. Recently, the involvement of HPV in the etiology of cervical cancer has been extended to prostate cancer. Epidemiological studies have shown that men with HPV infections in their 20's and 30's are five times more likely to develop prostate cancer in their 50's and 60's. In view of the potential significance of HPV infection, it would clearly be of interest to be able to routinely test samples for the presence of HPV. However, of the more than 54 genetic types of HPV which have been described (an HPV isolate is designated as a new "type" when it has less than 90% nucleotide homology in the E6, E& and L1 genes with previously characterized HPV types), only about 20% have been shown to be oncogenic. Thus, it is not sufficient to detect HPV. Meaningful diagnosis also requires the determination of the genetic type of any infecting virus. Web site: http://www.delphion.com/details?pn=US06503704__
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Nuclear inhibitor I-92 and its use for the production of a medicament Inventor(s): Kopun; Marijana (Heidelberg, DE), Napierski; Inge (Heidelberg, DE), Royer; Hans-Dieter (Berlin-Buch, DE), Stohr; Michael (Neckargerach, DE), Weitz; Jurgen (Durham, NC) Assignee(s): Dade Behring Marburg GmbH (Marburg, DE) Patent Number: 6,045,831 Date filed: January 19, 1994 Abstract: The present invention concerns a nuclear inhibitor which specifically inhibits the activity of sequence specific DNA enhancer binding proteins of Human Papilloma Virus (HPV) and the use of this nuclear inhibitor for the production of a medicament for treatment of human cervical cancer. Excerpt(s): The invention relates to a compound which regulates the activity of a protein which binds to a DNA enhancer sequence of human papillomavirus. Furthermore, the invention embraces the use of this compound for the production of a medicament for treating human cervical cancer and kits for the diagnosis of cervical tumors. Cervical
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cancer represents the second most frequent cancer in females on a worldwide scale. DNA of human papillomaviruses with high oncogenic potential is found in over 90% of cervical cancer biopsies. Two proteins E6 and E7 with transforming activity are encoded by viral early genes and their continuous expression is required for maintenance of the proliferative and transformed phenotype (Cancer Res. 48, 3780-3786 (1988); EMBO J, 8, 513-519 (1989)). The transforming activities of E6 and E7 proteins are at least in part explained by the fact that they interact specifically with products of tumor suppressor genes p105.sup.RB and p53. p105.sup.RB is the product of the retinoblastoma susceptibility gene (Cell, 60, 387-396 (1990)). HPV18 early gene expression is under control of the upstream regulatory region (URR), which has three domains, where the most 5'region, adjacent to the L1 gene, is E6 responsive and the most 3'region, which contains the early gene promoter, is E2 responsive (J. Virol., 62, 665-672 (1988)). The enhancer of papillomavirus type 18 consists of two functionally redundant domains, one is partially conserved between HPV18 and HPV16, both mediate strong transcriptional enhancement. The enhancer is located on a 230 nucleotide long RsaI-RsaI fragment, and can be subdivided into two functionally redundant domains of similar size, whose activity depends on cellular transregulatory factors (EMBO J., 6, 1339-1344 (1987); J. Virol., 61, 134-142 (1987)). After infection of normal cells, viral DNA is episomal and in rare cases viral DNA integrates into the host genome. In the integrates early genes are expressed at low level. In contrast, in cervix cancer cells, viral DNA is usually integrated and the early genes E6 and E7 are invariably expressed at high level. In most cases, the viral genome uses for the integration event coding sequences of the E2 gene, which encodes the viral transregulatory protein E2 (Nature, 314, 111-114 (1985)). Upon integration in E2 coding sequences this protein is inactivated, and the early gene promoter is no longer E2 dependent. It is assumed that the early gene promoter is then predominantly controlled by host cell factors (Cancer Cells, 1, 43-50 (1989)). The understanding of mechanisms which regulate the expression of the transforming genes is of critical importance for the understanding of cervical carcinogenesis and, consequently, important for the production of effective medicaments against cervical cancer. Web site: http://www.delphion.com/details?pn=US06045831__ •
Nucleic acid probes complementary to human papilloma virus nucleic acid Inventor(s): Carter; Nick M. (San Diego, CA) Assignee(s): Gen-Probe Incorporated (San Diego, CA) Patent Number: 6,583,278 Date filed: November 14, 1996 Abstract: The present invention describes oligonucleotides targeted to HPV Type 16 and/or Type 18 nucleic acid sequences which are particularly useful to aid in detecting HPV type 16 and or 18. The oligonucleotides can aid in detecting HPV Type 16 and/or Type 18 in different ways such as by acting as hybridization assay probes, helper probes, and/or amplification primers. Excerpt(s): This invention relates generally to nucleic acid probes complementary to Human Papillomavirus (hereafter "HPV") nucleic acids, methods of using such probes, and kits containing such probes. In particular, different types of oligonucleotide probes are described (including hybridization assay probes, helper oligonucleotides and amplification oligonucleotides) which are useful for detecting HPV Type 16 and/or Type 18 in a test sample, such as a vaginal swab, a cervical swab, a urethral swab, a
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tissue sample, a body fluid or an experimental solution. The following description of the background of the invention and references cited therein are not admitted to be prior art to the present invention. Papillomaviruses are small DNA viruses. These viruses are associated with and/or thought to be the causative agent of a range of benign conditions (including benign lesions and benign tumors). Papillomaviruses have also been associated with malignancies such as squamous cell carcinoma in patients having the autosomal disease epidermodysplasia verricruciformis, and with genital cancers in both males and females. Web site: http://www.delphion.com/details?pn=US06583278__ •
Nucleic acid probes of human papilloma virus Inventor(s): Bollen; Alex (Itterbeek, BE), Cravador; Alfredo (Rhode-St-Genese, BE), Herzog; Albert (Eppegem, BE), Houard; Sophie (Brussels, BE) Assignee(s): Ire-Celltarg S.A. (Fleurus, BE) Patent Number: 4,983,728 Date filed: July 28, 1988 Abstract: The present invention relates to probes of nucleic acids useful for detecting indifferently the various types of human papilloma virus, particularly HPV1a, HPV5, HPV6b, HPV8, HPV11, HPV16, HPV18 and HPV33, especially a probe comprising a labelled sequence of nucleic acids, characterized in that it comprises the oligomer of twelve nucleotides X-A-A-A-A-C-G-A-A-A-G-X, with X=T or U, or its complement by interchanging A and X on the one hand, C and G on the other hand. The present invention also relates to specific probes of nucleic acids for the detection of human papilloma for each of the types HPV1a, HPV5, HPV8, HPV11, HPV16, HPV18 and HPV33, as well as specific probes of sub-groups of the virus HPV16, HPV18, HPV33 or HPV16 and HPV18 only or again HPV5 and HPV8 only. Excerpt(s): The technical field of the present invention is that of probes constituted by labelled, mono-strand DNA or RNA nucleic acid sequences. Such probes are well known in the state of the art and may be obtained by various routes particularly by genetic engineering or by manual or automatic direct synthesis. These nucleic acid sequences have the property of being matched and of forming hybrids with complementary DNA sequences, as the case may be, denaturated previously, if the latter were initially bicatenary or mRNA. This denaturation can be done after incubation in a medium of high ionic strength and at high temperature or in a basic medium. These hybrids are then detectable. Web site: http://www.delphion.com/details?pn=US04983728__
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Nucleotide sequences useful as type specific probes, PCR primers and LCR probes for the amplification and detection of human papilloma virus, and related kits and methods Inventor(s): Bouma; Stanley R. (Mundelein, IL), Joseph; Jeffrey L. (Cherry Hill, NJ), Laffler; Thomas G. (Libertyville, IL), Marshall; Ronald L. (Zion, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,484,699 Date filed: September 30, 1994 Abstract: Short nucleotide sequences of human papilloma virus useful for the determination of the presence and type of human papilloma virus present in a test sample. The sequences provided can be amplified by polymerase chain reaction or ligase chain reaction. The sequences provided also can be hybridized by standard slot-, dot- or replica-blot procedures. Methods and kits also are provided for the detection of human papilloma virus in a test sample and the determination of the type of human papilloma virus present in the test sample. Excerpt(s): This invention relates generally to human papilloma virus, and more particularly, relates to nucleotide sequences of short strands of human papilloma virus which can be amplified and/or used to determine the presence of human papilloma virus products in a test sample, and which also can be amplified and/or used to determine the specific type of human papilloma virus of types 6, 11, 16, 18, 31, 33 and 61 present in the test sample. Human papilloma virus (HPV) is recognized as a venereally-transmitted disease of the anogenital tract which often is associated with the pathogenesis of cervical cancer and its precursor lesions. More than 56 types of HPV have been characterized. Of these, at least 21 types infect the anogenital tract. L. Gregoire et al., J. Clin. Micro 27 (12):2660-2665(1989). These mucosotropic viruses are associated most frequently with benign condyloma or latent infections. However, the presence of HPV in premalignant lesions and invasive cancers, particularly of the cervix, may reflect the oncogenic potential of these viruses. See P. M. Howley, in Important Advances in Oncology, D. T. DeVita, Jr. et al., eds., J. B. Lippincott, Philadelphia, Pa. (1987) at pages 55-73. Certain HPV types, namely, HPV type 16 and type 18, and to a lesser extent HPV types 31, 33 and 35, are found in a high proportion of invasive cervical cancers and their metastases. However, many HPV types which infect the anogenital tract, such as HPV types 6 and 11, are found most commonly in benign condyloma and only rarely are found in invasive cancers. HPV detected in the anogenital tract can be classified broadly as low risk papilloma viruses (HPV types 6 and 11), intermediate risk papilloma viruses (HPV types 31, 33 and 35) or high risk papilloma viruses (HPV types 16 and 18), based on the association of the particular HPV type with malignancy. A. T. Lorincz et al., J. Nat'l. Cancer Inst. 79:671 (1987). Thus, the detection of the presence of HPV and the determination of the specific type of HPV can provide a diagnostic and prognostic tool useful for determining the clinical significance associated with certain HPV types. The early detection of HPV by sensitive and specific reagents and methodologies also could provide earlier therapeutic management and counseling. Web site: http://www.delphion.com/details?pn=US05484699__
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PCR diagnosis of human papilloma virus type 16 Inventor(s): Bavin; Peggy J. (London, GB2), Emery; Vincent C. (Hampstead, GB2), Walker; Patrick (Hampstead, GB2) Assignee(s): Royal Free Hospital School of Medicine (London, GB2) Patent Number: 5,501,947 Date filed: March 12, 1993 Abstract: The invention provides oligonucleotides (A): and (B): and their derivatives. These oligos may be used as a pair of primers for the detection of HPV16 (SEQ ID NO:3) DNA in a sample, without false positives arising due to the presence of other HPV strains. Kits containing the primers and the use of the primers to screen populations are provided. Excerpt(s): This application originates from International Application No. PCT/GB91/01212, filed Jul. 19, 1991, based on United Kingdom Application No. 901584.2, filed Jul. 19, 1990. This invention relates to an improved method of detection of human papillomavirus (HPV), in particular HPV using the polymerase chain reaction (PCR). Papillomaviruses are a group of closely related viruses that produce a spectrum of diseases in Man and other mammals. At present there are in excess of 57 different types of human papillomaviruses. The definition of a new type is that it possesses less than 50% cross hybridisation with the DNA of known species in the liquid phase according to a standard protocol. A number of human diseases have been attributed to specific papillomavirus types; for example, plantar warts--papillomavirus type 1 and common warts--papillomavirus type 7. Web site: http://www.delphion.com/details?pn=US05501947__
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Topical virucidal composition for treatment of mucocutaneous tissue Inventor(s): Kim; Wendy Y. (968 E. Green Oaks Dr., Bountiful, UT 84010), Marcus; Stanley (1400 E. Federal Way, Salt Lake City, UT 84102) Assignee(s): none reported Patent Number: 5,182,104 Date filed: July 16, 1991 Abstract: This invention pertains to a topically applied composition with a virucidal impact on mucocutaneous tissue. Ingredients essential to the efficacy of the formulated combination include a polyethylene glycol polymer known as Nonoxynol-9("N-9")in admixture with selected fat soluble vitamins A, D and E in the form of vegetable oil (and) retynyl palmitate (and) ergocalciferol together with tocopherol acetate. The invention is directed particularly to inactivation of herpes virus and human papilloma virus as manifested in cold sores, lesions, fever blisters, canker sores and warts. The N-9 contains viral activity while the vitamins effect restoration and strengthening of the damaged tissue cells. Excerpt(s): This invention relates to an improved anti-microbial agent. More particularly, this invention is specifically directed to an additive for water-based polymerized compositions and provides an ethylene glycol-based composition for topical anti-viral treatment of mucocutaneous tissue. Ethylene glycol, an inexpensively available organic chemical, is readily polymerized. Polyethylene glycol (PEG) is widely used in our society. A PEG polymer with the molecular weight of 968, commonly
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referred to as nonoxynol-9 or N-9, is a viscous liquid that has long been used as a lubricant and spermicide in concentrations of 2%-5% in over-the-counter (OTC) preparations, e.g., Ortho-creme, Gentersal, Delfen. Products known commercially as ViroNox-9 and aidsPLUS+ marketed by MicroBio Products, Inc. of Tempe, Ariz. and Medical Diagnostic Technologies, Inc. dba MeDiTech of Ventura, Calif. respectively, though directed toward cleansing of body surfaces based on other active ingredients, also contain N-9 in concentrations of approximately 2% and are known to provide additional protection against microbiological contamination. The safety, absence of toxicity and freedom from any harmful side effects of these preparations is attested to by long, continued and repeated use. The spermicide N-9 has been shown to be virucidal and to reduce the frequency of infections due to both viral and bacterial sexually transmitted diseases. It has been suggested that this anti-viral action of N-9 may be the reason why women who use spermicides are far less likely to have cervical cancer in view of the fact that a leading cause of cervical cancer is almost undoubtedly herpes virus. A recent review of scientific archival reports by B. North in Journal of Reproductive Medicine, 33:307, 1988, concludes that the advice of former U.S. Surgeon General Everett Koop be followed for widespread use of N-9 in contraceptive devices as an aid in reducing risk from bacterial and viral infection passed by sexual intercourse. Of course, this includes herpes infection. Web site: http://www.delphion.com/details?pn=US05182104__ •
Transgenic mice expressing HPV early region oncogene develop progressive epithelial neoplasia Inventor(s): Arbeit; Jeffrey M. (San Francisco, CA), Hanahan; Douglas (San Francisco, CA), Howley; Peter M. (Wellesley, MA) Assignee(s): The Regents of the University of California (Rockville, MD), The United States of America as represented by the Secretary of Health (Washington, DC) Patent Number: 5,698,764 Date filed: June 9, 1994 Abstract: The present invention relates to improved models for progressive epithelial neoplasias and methods for their use. In particular, the invention provides transgenic mice comprising a human papilloma virus early region oncogene operably linked to a promoter which directs expression of the oncogene in a transient amplifying cell in the mice. Excerpt(s): This invention pertains to the field of transgenic non-human animals. In particular this invention pertains to a Wansgenie animal that exhibits progressive epithelial neoplasia and methods of screening for therapeutics for progressive epithelial neoplasia. The most common malignancies in clinical practice arise in epithelia. An epithelium is the lining of a body surface that is exposed to the outside world, which places this tissue at risk for repeated damage from a variety of agents in the environment. Environmental carcinogens are the main suspects as major contributors to the development and spread of epithelial cancers. Examples of the most common epithelial cancers include lung, colon and breast carcinomas which are also the most prevalent cancers in industrialized countries. In the third world epithelial cancers such as liver and uterine cervical cancers account for the majority of cancer deaths. All of these cancers are associated with a diverse array of carcinogen exposures including cigarette smoke, estrogenic contaminants, toxic molds infecting grains, and infection with genital DNA tumor viruses. A feature shared by most epithelial cancers is their
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multi-step progression to malignancy and are thus referred to as progressive epithelial neoplasias. The concept of multi-step carcinogenesis means that cancers do not appear "out of the blue", but evolve slowly over time during which the surrounding tissue becomes increasingly abnormal, and serves as fertile soil for the emergence of a full blown malignancy. Web site: http://www.delphion.com/details?pn=US05698764__ •
Variants of human papillomavirus antigens Inventor(s): Cox; John Cooper (Bullengarook, AU), Edwards; Stirling John (Caburg, AU), Frazer; Ian (St. Lucia., AU), Webb; Elizabeth Ann (Eltham, AU) Assignee(s): CSL Limited (Parkville, AU), The University of Queensland (St. Lucia, AU) Patent Number: 6,004,557 Date filed: September 22, 1997 Abstract: Variants of human papilloma virus (HPV) E6 and E7 able to elicit a humoral or cellular immune response against HPV in a host animal but not being celltransforming in the host animal are disclosed, and are useful in treatment or prevention of diseases or conditions involving HPV. Excerpt(s): This invention relates generally to variants of human papilloma virus (HPV) antigens, and in particular it relates to non-transforming variants of HPV antigens which are suitable for use in vaccines. The invention also extends to vaccine compositions which include these variants of HPV antigens as active immunogens, as well as to methods of use of these variants to elicit an immune response against HPV. Papillomaviruses are small DNA viruses that infect a variety of animal species. Some are associated with the development of malignancies in their natural hosts. Over 60 types of human papillomavirus (HPV) have been identified. These infect humans at a variety of body locations and are responsible for common skin warts, laryngeal papillomas, genital warts and other wart-like lesions. Genital HPV infections are particularly common and a number of HPV types, but most frequently types 6, 11, 16 and 18, infect the genital tract in both men and women. In women, HPVs infect various portions of the genital tract including the cervix. iii latency, where the only sign of infection is the presence of HPV DNA. Web site: http://www.delphion.com/details?pn=US06004557__
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Vectors for DNA immunization against cervical cancer Inventor(s): Cao; Shi-Xian (Etobicoke, CA), Gajewczyk; Diane M. (Toronto, CA), Klein; Michel H. (Willowdale, CA), Moingeon; Phillipe (F-Pommiers, FR), Persson; Roy (North York, CA), Rovinski; Benjamin (Thornhill, CA), Tartaglia; James (Schenectady, NY), Yao; Fei-Long (North York, CA) Assignee(s): Connaught Laboratories Limited (Toronto, CA) Patent Number: 6,235,523 Date filed: September 3, 1999 Abstract: Vectors for DNA immunization against cervical cancer comprise a nucleic acid molecule encoding at least one non-toxic T-cell epitope of the E6 and/or E7 antigens of a strain of human papilloma virus (HPV) associated with cervical cancer, such as HPV-
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16, and a promoter operatively coupled to the nucleic acid molecule for expression of the nucleic acid molecule in a host to which the vector is administered. Excerpt(s): The invention is concerned with immunotherapy of cancer, specifically cervical cancer. Cervical cancer is the second most common cause of cancer-related deaths in women worldwide. There is both epidemiological and experimental data which links the etiology of cervical cancer to infection with human papilloma virus (HPV) types 16 and 18. The HPV virus is prevalent in 35 to 40% of young women. Although treatment of early stage disease is relatively successful, recurrent disease is found in 15% of the patients. The outcomes of patients with recurrent disease are relatively poor. Hence, there is a need for a novel therapeutic approach (refs. 1, 2, 3-various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosure of these references are hereby incorporated by reference into the present disclosure). The strong association of HPV infection and cervical cancer suggests that a viral antigenspecific immunotherapeutic approach may be a feasible strategy in the treatment of cervical cancer. The goal of specific immunotherapy is to stimulate the immune response of a tumour-bearing patient to attack and eradicate tumour lesions. This strategy has been made feasible with the identification of tumour associated antigens (TAA). The strong association between HPV-16 infection and cervical cancer has made this disease a good candidate for immunotherapeutic intervention (ref. 4). Web site: http://www.delphion.com/details?pn=US06235523__ •
Water-soluble derivatives of epipodophyllotoxin, process for their preparation, their use as medicinal products and their intended use in anti-cancer treatments Inventor(s): Guminski; Yves (Lagarrigue, FR), Hill; Bridget (Castres, FR), Imbert; Thierry (Viviers-les-Montagnes, FR), Monse; Barbara (Castres, FR), Robin; Jean-Pierre (Le Mans, FR) Assignee(s): Pierre Fabre Medicament (Boulogne, FR) Patent Number: 6,107,284 Date filed: April 21, 1997 Abstract: Water-soluble derivatives of epipodophyllotoxin, process for their preparation and their use for the treatment of rheumatoid arthritis, complaints caused by human papilloma virus and cancer. Excerpt(s): Among the class of epipodophylloids, certain compounds such as etoposide or teniposide, which are semisynthetic compounds derived from epipodophyllotoxin, obtained from natural lignan, are used in the preparation of medicinal products for treating many forms of cancer. They are currently considered as major products of the therapeutic arsenal. Among the various cancers treated with compounds of this type, mention may be made of alveolar lung cancer, embryonic tumors, neuroblastomas, cancer of the kidney, lymphomas, Hodgkin's disease, acute leukemias, and even breast cancer. Etoposide is advantageously used in combination with other anticancer products and in particular platinum derivatives such as cisplatin. The major drawback of this derivative, and likewise of its related derivative teniposide, is its lack of water-solubility. No water-soluble forms for intravenous administration exist on the market. On the contrary, the dissolution is currently carried out in partially non-aqueous solvents, requires administration by slow infusion and gives rise to certain undesirable or even
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toxic effects. There is thus a need for water-soluble forms for products derived from this class of compounds in order to improve the administration to the patient, as well as its bioavailability. The present invention thus relates to etoposide derivatives which are water-soluble by means of the presence of phosphate or carboxylate functional groups whose organic or inorganic addition salts form soluble species in water. This aqueous formulation has the advantage of being less toxic and easier to administer than the forms currently marketed. Web site: http://www.delphion.com/details?pn=US06107284__
Patent Applications on Human Papilloma Virus As of December 2000, U.S. patent applications are open to public viewing.9 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 human papilloma virus: •
Assessment of human papilloma virus-related disease Inventor(s): Lazar, James G.; (Bethesda, MD), Lorincz, Attila T.; (North Potomac, MD) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20020127545 Date filed: October 4, 2001 Abstract: This invention provides novel methods for assessing HPV infection. Gene expression levels are used to assess the progression of HPV infection from benign to malignant growth. Also provided are kits for carrying out the methods of this invention. Excerpt(s): The detection and diagnosis of disease is of obvious importance for the treatment of disease. Numerous characteristics of diseases have been identified and many are used for the diagnosis of disease. 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. An aspect of the present invention relates to human papilloma virus (HPV), which induces benign epithelial proliferations of the skin and mucosa in humans and is associated with anogenital neoplasias and carcinomas. The intact DNA of HPV is supercoiled and thus resembles an endless loop of twisted telephone handset cord. Inside this shell, the viral DNA is packaged in and around proteins from the cell nucleus, histones, and associated peptides, into a structure that resembles cellular chromatin. (Turek, (1994)). Human papillomaviruses characterized to date are associated with lesions confined to the epithelial layers of skin, or oral, pharyngeal, respiratory, and, most importantly, anogenital mucosae. Specific human papillomavirus types, including HPV 6 and 11, frequently cause benign mucosal lesions, whereas other types, HPV 16, 18, and a host of other strains, are predominantly found in high-grade lesions and cancer. All human and animal papillomaviruses appear to share a similar genetic organization, although there are differences in the functions of individual viral genes and in their regulation. The
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This has been a common practice outside the United States prior to December 2000.
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most common genital HPV type associated with cervical carcinoma, HPV 16, has been studied most extensively. All large open reading frames (ORFs) in HPV are on one DNA strand. Papillomaviral mRNAs appear to be transcribed solely from a single strand in infected cells. The viral genome can be divided into three regions, the upstream regulatory region (URR), or long control region (LCR), containing control sequences for HPV replication and gene expression, the viral early gene region, encoding, among others, the E2, E6 and E7 genes, and the late region, encoding the L1 and L2 genes. (Turek, (1994)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Broad spectrum microbicidal and spermicidal compositions, devices, and methods Inventor(s): Howett, Mary K.; (Hershey, PA), Krieder, John W.; (Palmyra, PA) Correspondence: Dickstein Shapiro Morin & Oshinsky Llp; 2101 L Street NW; Washington; DC; 20037-1526; US Patent Application Number: 20030108509 Date filed: August 15, 2002 Abstract: Microbicidal and spermicidal devices, methods, and compositions containing sodium dodecyl sulfate or related anionic surfactants as active ingredients for the prevention and control of pregnancy and sexually transmitted disease, including conditions caused by non-enveloped viruses such as human papilloma virus. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/081,199, filed May 19, 1998. The present invention relates to the prevention of pregnancy and the prevention and control of sexually transmitted and other diseases with the use of compositions having broad spectrum microbicidal and spermicidal activity, including the ability to inactivate particularly resistive pathogens such as human papillomaviruses and other non-enveloped viruses. Sexually transmitted diseases (STDs) are among the most prevalent and communicable diseases and continue to be a significant public health problem. It is estimated that more than 250 million people worldwide, and close to 3 million people in the United States, are infected annually by gonorrhea. Annual worldwide incidence of syphilis is estimated at 50 million people, with 400,000 in the United States annually needing treatment. More recently, the human immunodeficiency virus (HIV), resulting in fatal acquired immunodeficiency syndrome (AIDS), has spread rapidly in both homosexual and heterosexual groups. The World Health Organization (WHO) and the National Institute for Health (NIH) recommend that mothers who are HIV positive not nurse their babies because of a high risk of transmitting HIV in breast milk. However, failure to nurse often results in infant malnutrition, diarrhea, dysentery, and other infectious diseases, because areas with high endogenous HIV often also have low food stores and poor hygienic quality of food and water. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for treating skin ailments Inventor(s): Elisyevich, Irina; (Katzrin, IL), Mairon, Omri; (Zichron Yaakov, IL), Nir, Moire Marx; (Misgav, IL), Stein, Oded; (Jerusalem, IL) Correspondence: G.E. Ehrlich (1995) LTD.; C/o Anthony Castorin; Suite 207; 2001 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030133893 Date filed: January 15, 2002 Abstract: Compositions that comprise a polymer entrapping an oxidizing agent are disclosed. The disclosed compositions are used in the treatment of skin ailments such as human papilloma virus infections. Excerpt(s): The present invention relates to compositions and methods for treating skin ailments and, more particularly, to the use of a conformable and/or spreadable polymer as a sustained release carrier for an oxidizing agent entrapped therein or thereby and its use in the treatment of skin ailments such as, but not limited to, human papilloma virus infections. Human papilloma virus (HPV) infections are common infections of the outer layer of the skin, which affect most persons sometime during their lifetime. To date, more than sixty types of HPVs have been identified. HPV infections typically emerge as skin warts, which include, for example, common warts (verruca vulgaris), plantar warts, palmar warts, planar warts (verruca plana), mosaic warts, and venereal warts (condyloma accuminatum). These skin growths are unsightly and irritating, and although the majority of such infections are benign and self-limited, there are subtypes of papilloma virus that are considered pre-malignant in certain clinical settings. Therefore, the removal of emerged skin warts is highly recommended. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Diindolylmethane for the treatment of HPV infection Inventor(s): Zeligs, Michael A.; (Boulder, CO) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030096855 Date filed: April 5, 2002 Abstract: New methods and compositions are disclosed that comprise the phytochemical Diindolylmethane, alone or in combination with immune potentiating steroids. These methods and compositions are utilized to treat subjects suffering from common cutaneous warts (verrucae) and Human Papilloma Virus (HPV) related conditions of the oropharynx, larynx, genitalia, and uterine cervix. Excerpt(s): This application claims priority under 35 U.S.C. 119(e) from provisional application No. 60/337,563 filed on Oct. 23, 2001. The present invention relates to compositions and methods for the treatment of verrucae (common skin warts) and related, oral-genital infections with the human papilloma virus (HPV), using Diindolylmethane, a natural phytochemical found in cruciferous vegetables. The methods of the invention include the use of Diindolylmethane alone and in combination with immune potentiating steroids. Diindolylmethane ("DIM") is a member of the family of dietary indoles discovered in cruciferous vegetables. Diindolylmethane and its unstable precursor, Indole-3-carbinol ("I3C"), have been identified in cruciferous
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vegetables, including broccoli, cauliflower, cabbage and Brussels sprouts (Bradfield, C. A. and Bjeldanes, L. F., "High performance liquid chromatographic analysis of anticarcinogenic indoles in Brassica oleracea", J. Agric. Food Chem., 35:46-49 (1987)). After the release of I3C from parent glucosinolates in cruciferous plants during crushing or chewing, Diindolylmethane is formed enzymatically. Also, Diindolylmethane is one of many indole products derived from I3C which are further generated during digestion as a result of acid-catalyzed reactions in the stomach and intestine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Human pancreatic pluripotential stem cell line Inventor(s): Madhukar, Burra V.; (Okemos, MI), Olson, Lawrence K.; (East Lansing, MI), Trosko, James E.; (Okemos, MI), Tsao, Ming Sound; (Toronto, CA), VanCamp, Loretta; (East Lansing, MI) Correspondence: Mcleod & Moyne; 2190 Commons Parkway; Okemos; MI; 48864 Patent Application Number: 20030003088 Date filed: April 30, 2002 Abstract: A human pancreatic ductal epithelial cell line immortalized with the human papilloma virus E6 and E7 genes which has stem cell-like characteristics and which can be induced to differentiate into ductal-like cells and beta-like cells that produce insulin. The immortal cells or derivative thereof are useful for treating insulin-dependent diabetes and in assays for determining the ability of a chemical to induce pancreatic stem cell differentiation or malignancy. Excerpt(s): Not Applicable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human papilloma virus treatment Inventor(s): Boux, Leslie J.; (Victoria, CA), Goldstone, Stephen E.; (New York, NY), Neefe, John R.; (Devon, PA), Siegel, Marvin; (Blue Bell, PA), Winnett, Mark T.; (Phoenixville, PA) Correspondence: Lee Crews, PH. D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020110566 Date filed: June 26, 2001 Abstract: Disclosed is a method of treating a wart in a subject by administering to the subject a composition containing (1) a heat shock protein or an immunostimulatory fragment thereof, and (2) a protein of a human papilloma virus or an antigenic fragment thereof. Also disclosed is a method of treating a human papilloma virus infection in a subject infected or suspected of being infected with a human papilloma virus of a first type by administering to the subject a composition containing (1) a heat shock protein or an antigenic fragment thereof, and (2) a protein of a human papilloma virus of a second type or an antigenic fragment thereof, where the first type and second type are different.
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Excerpt(s): This application claims priority from U.S. Provisional Application No. 60/214,202, filed Jun. 26, 2000, the content of which is incorporated herein by reference in its entirety. The invention relates to therapies for human papilloma virus infections. Infection with human papilloma virus (HPV) is common. HPV can be transmitted sexually, and it is estimated that 20-80% of sexually active adults have been infected. While a majority of infections are asymptomatic, infection can lead to the development of genital warts (which have a prevalence of about 1-5% among adults) and cancer of the anogenital tract. Another type of cancer, cervical cancer, is strongly associated with HPV (Frazer, Genitourin. Med. 72:398-403, 1996). HPV types 6, 11, 16, 18, 31, and 33 are often associated with an increased risk of cancer, with types 16 and/or 18 being detected in more than 90% of cervical carcinomas (van Driel et al., Ann. Med. 28:471-477, 1996). Types 6 and 11 are also associated with anogenital warts. For reviews of papilloma viruses and their associated pathologies, see Shah et al., "Chapter 66: Papillomaviruses," In: Virology, 3rd Edition, Fields et al., Eds., Raven Press, Philadelphia, pp 2077-2109, 1996, and zur Hausen, J. Natl. Cancer Inst. 92:690-698, 2000. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Inhibitors of papilloma virus Inventor(s): Goudreau, Nathalie; (Laval, CA), Hache, Bruno; (Laval, CA), Ogilvie, William W.; (Ottawa, CA), O'Meara, Jeffrey; (Laval, CA), White, Peter; (Laval, CA), Yoakim, Christiane; (Laval, CA) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury RD; P O Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030064985 Date filed: December 17, 2001 Abstract: A compound of formula (I) or its enantiomers or diastereoisomers thereof: 1wherein: A,; X, W, R.sup.1, Y; R.sup.3; and R.sup.4 are as defined herein.The compounds of the invention may be used as inhibitors of the papilloma virus E1-E2DNA complex. The invention further provides a method of treating or preventing human papilloma virus infection. Excerpt(s): Benefit of U.S. Provisional Application Serial No. 60/256,706, filed on Dec. 18, 2000 is hereby claimed and said Application in incorporated herein by reference. The present invention relates to compounds, compositions and methods for the treatment of papilloma virus (PV) infection, particularly human papilloma virus (HPV). In particular, the present invention provides novel indane derivatives, pharmaceutical compositions containing such derivatives and methods for using these compounds in the treatment of papilloma virus infection. More particularly, the present invention provides compounds, compositions and methods for inhibiting papilloma virus DNA replication by interfering with the E1-E2-DNA complex during initiation of DNA replication. Papillomaviruses are non-enveloped DNA viruses that induce hyperproliferative lesions of the epithelia. The papillomaviruses are widespread in nature and have been identified in higher vertebrates. Viruses have been characterized, amongst others, from humans, cattle, rabbits, horses, and dogs. The first papillomavirus was described in 1933 as cottontail rabbit papillomavirus (CRPV). Since then, the cottontail rabbit as well as bovine papillomavirus type 1 (BPV-1) have served as experimental prototypes for studies on papillomaviruses. Most animal papillomaviruses are associated with purely epithelial proliferative lesions, and most lesions in animals are cutaneous. In the human there are more than 75 types of papillomavirus that have
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been identified and they have been catalogued by site of infection: cutaneous epithelium and mucosal epithelium (oral and genital mucosa). The cutaneous-related diseases include flat warts, plantar warts, etc. The mucosal-related diseases include laryngeal papillomas and anogenital diseases comprising cervical carcinomas (Fields, 1996, Virology, 3rd ed. Lippincott--Raven Pub., Philadelphia, N.Y.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for treating cervical cancer Inventor(s): Chandrasekher, Yasmin A.; (Mercer Island, WA), McKernan, Patricia A.; (Seattle, WA) Correspondence: Paul G. Lunn, ESQ.; Zymogenetics, INC.; 1201 Eastlake Avenue East; Seattle; WA; 98102; US Patent Application Number: 20030161811 Date filed: December 17, 2002 Abstract: Use of Interleukin-20 for treating cervical cancer or cells infected with human papilloma virus. IL-20 can be administered alone or in conjunction with radiation or chemotherapeutic agents or surgical excision of the involved cells or lesions. Excerpt(s): This claims the benefit under 35 U.S.C.sctn.119 (e) of U.S. Provisional Application No. 60/341,783 filed on Dec. 17, 2001. According to the American Cancer Society, 12,800 new cases of invasive cervical cancer would be diagnosed in the United States in 1999. During the same year, 4800 patients were expected to die of the disease. This represents approximately 1.8% of all cancer deaths in women and 18% of gynecological cancer deaths. However, for women aged 20 to 39 years of age, cervical cancer is the second leading cause of cancer deaths. Molecular and epidemiologic studies have demonstrated a strong relationship between human papillomavirus (HPV), cervical intraepithelial neoplasia, (CIN), and invasive carcinoma of the cervix. Thus, there is a need to develop new therapeutic entities for the treatment of human papillomavirus infection, cervical intraepithelial neoplasia and carcinoma of the cervix. The present invention fills this need by administering interleukin-20 (IL-20) to a mammalian having cervical cancer. IL-20 can also be used to treat a human papillomavirus infection. The present invention also provides a method for inhibiting the growth of cervical cancer cells by bringing IL-20 into contact with said cancerous cervical cells. Interleukin-20 (formally called Zcyto10) can be produced according to the method described in International Patent Application No. PCT/US98/25228 filed on Nov. 25, 1998. The human IL-20 polypeptide is comprised of a sequence of 176 amino acids with the initial Met as shown in SEQ ID NO: 1 and SEQ ID NO:2. It is believed that amino residues 1-24 are signal sequence, and the mature IL-20 polypeptide is represented by the amino acid sequence comprised of residues 25, a leucine, through amino acid residue 176, a glutamic acid residue, also defined by SEQ ID NO:12. Another embodiment of the present invention is defined by the sequences of SEQ ID NO: 3 and SEQ ID NO: 4. The polypeptide of SEQ ID NO: 4 is comprised of 151 amino acid residues wherein amino acids 1-24 comprise a signal sequence and the mature sequence is comprised of amino acid residues 25, a leucine, through amino acid 151 a glutamic acid, also defined by SEQ ID NO: 13. Another active variant is comprised of amino acid residues 33, a cysteine, through amino acid residue 176 of SEQ ID NO:2. This variant is also defined by SEQ ID NO:26. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for co-stimulation of immunological responses to peptide antigens Inventor(s): Berzofsky, Jay; (Bethesda, MD), Khleif, Samir; (Silverspring, MD) Correspondence: Townsend And Townsend And Crew; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020044948 Date filed: March 14, 2001 Abstract: Method for eliciting an immune response in a vertebrate subject are provided involving administration of a peptide antigen to the subject in a coordinated vaccination procedure that also involves administration of a non-viral vector that encodes a T cell co-stimulatory molecule. The peptide antigen contains at least one T cell epitope and may include an epitope of a tumor antigen or an antigen of a viral or non-viral pathogen. Epitopes from tumor antigens may represent fragments or partial amino acid sequences of p53, ras, rb, mcc, apc, dcc; nfl; VHL; MEN1, MEN2, MLM, Her-2neu, CEA, PSA; Muc1, Gp100, tyrosinase, or MART1 proteins, and often span a mutation identified in the tumor antigen. Various viral antigens may be selected, for example antigens identified in a human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpes simplex virus (HSV) or human papilloma virus (HPV), for production of peptide antigens corresponding to immunogenic epitopes of the viral antigen. The peptide antigen is administered simultaneously or sequentially with administration of the vector encoding the co-stimulatory molecules. Co-stimulatory molecules useful for coordinate administration with peptide antigens to elicit an enhanced T cell-mediated immune response may be selected from B7-1, B7-2, B7-3, ICAM1, ICAM2, LFA1 or LFA2. The peptide antigen and non-viral vector encoding the T cell co-stimulatory molecule are administered to proximal target sites selected from the same, or closely-adjacent, intradermal, subcutaneous, mucosal or intratumoral sites. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/189,396, filed by Samir N. Khleif, et al., on Mar. 15, 2000. For most viruses and nonviral pathogens, the greatest levels of host immunity are stimulated by natural infection. For viruses in particular, attempts to artificially elicit high-level host immunity frequently involve the use of live attenuated vaccines. However, such live attenuated viruses may be poorly suited for uninfected human recipients. Particularly in the case of retroviruses, such as HIV, inoculation of the attenuated vaccine organism may impose substantial risks, including possible integration of viral genome into the host cellular chromosomes and induction of immune disorders. To reduce these risks, an alternative vaccination method is to use pure, well-characterized proteins or synthetic peptides as immunogens to elicit humoral and/or cellular immunity. It is well recognized that synthetic peptides incorporating immunogenic epitopes of a native pathogen can induce antibodies reactive with their cognate sequences in the native proteins. Likewise, several studies have reported the ability to immunize mammalian hosts with peptides to induce virus-specific or bacteria-specific cytotoxic T lymphocytes (CTLs) (Aichele et al., J. Exp. Med. 171:1815-1820, 1990; Schulz et al., Proc. Natl. Acad. Sci. USA 88:991-993, 1991; Kast et al., Proc. Natl. Acad. Sci. USA 88:2283-2287, 1991; Harty et al., J. Exp. Med. 175:15311538,1992; Hart et al., Proc Natl. Acad. Sci. USA 88:9448-9452, 1991; U.S. Pat. No. 4,599,230, and U.S. Pat. No. 4,599,231, each incorporated herein by reference). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Multivalent vaccination using recombinant adenovirus Inventor(s): Wang, Danher; (Mt. Pleasant, SC) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20030219458 Date filed: February 5, 2003 Abstract: Genetic vaccines and multivalent vaccination methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant adenovirus is provided for eliciting immune response of a host to viral pathogens. The recombinant adenovirus comprises: a first antigen sequence that is heterologous to a native progenitor of the recombinant adenovirus and encodes a first viral antigen from a first pathogenic virus, expression of which is under the transcriptional control of a first promoter; and a second antigen sequence that is heterologous to a native progenitor of the recombinant adenovirus and encodes a second viral antigen from a second pathogenic virus, expression of which is under the transcriptional control of a second promoter. Expression of the first and second antigen sequences elicit an immune response directed against the first and second viral antigens upon infection of the host by the recombinant virus. The genetic vaccines can be used for immunizing a host against a wide variety of pathogens, such as HIV, Ebola virus, Marburg virus, hepatitis virus, influenza virus, respiratory syncytial virus, and human papilloma virus. Excerpt(s): This application is a continuation of U.S. patent application entitled "GENETIC VACCINE AGAINST HUMAN IMMUNODEFICIENCY VIRUS", application Ser. No. 10/003,035, Filed: Nov. 1, 2001, which is a continuation-in-part of PCT application entitled "GENETIC VACCINE THAT MIMICS NATURAL VIRAL INFECTION AND INDUCES LONG-LASTING IMMUNITY TO PATHOGEN", application Ser. No.: PCT US01/18238, Filed: Jun. 4, 2001, which is a continuation-inpart of U.S. patent application entitled "GENETIC VACCINE THAT MIMICS NATURAL VIRAL INFECTION AND INDUCES LONG-LASTING IMMUNITY TO PATHOGEN", application Ser. No.: 09/585,599, Filed: Jun. 2, 2000. The above applications are incorporated herein by reference. This invention relates to vaccines for stimulating immune responses in human and other hosts, and, in particular, relates to recombinant viruses that express heterologous antigens of human immunodeficiency virus (HIV) in a host and elicit immune response to HIV infection. Current techniques for developing vaccines are largely based on the concept of using denatured virus or purified viral proteins made from bacteria. These types of vaccines may be effective for only a limited number of infectious agents, and the protection rates are limited. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Papilloma virus sequences Inventor(s): Ertl, Peter F.; (Stevenage, GB), Gough, Gerald W.; (Stevenage, GB), Parmar, Vanita; (Stevenage, GB), Ring, Christopher Jeffrey Alan; (Stevenage, GB), Walcott, Sarah Marina; (Stevenage, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020137720 Date filed: August 24, 2001 Abstract: The present invention relates to methods and compositions useful in the treatment and prevention of human papilloma virus infections and the symptoms and diseases associated therewith. More particularly, the invention relates to polynucleotide sequences which encode human papilloma virus (HPV) amino acid amino acid sequences, wherein the codon usage pattern of the polynucleotide sequences resemble those of highly expressed mammalian genes. Excerpt(s): The present invention relates to methods and compositions useful in the treatment and prevention of human papilloma virus infections and the symptoms and diseases associated therewith. Papilloma virus infections have been observed in a variety of species, including sheep, dogs, rabbits, monkeys, cattle and humans. Human papilloma viruses (HPV) have been classified into more than 80 types (Epidemiology and Biology of Cervical Cancer. Seminars in Surgical Oncology 1999 16:203-211). New (novel) types are defined as those where the L1 gene displays less than 90% sequence identity to L1 sequences from previously identified types, whilst a sub-type displays between 90% and 98% L1 sequence identity, and a variant more than 98% sequence identity (to the prototypical (parent) type). Papilloma viruses generally infect epithelia, but the different HPV types cause distinct diseases. For example, types 1-4, 7, 10 and 2629 cause benign cutaneous warts, types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 are associated with cervical cancers and types 6 and 11 are implicated in genital warts (non-malignant condylomata of the genital tract). The majority of genital warts (>90%) contain HPV genotypes 6 and 11. Whilst HPV-6 is the most prevalent genotype identified in single infections, both HPV-6 and HPV-11 may occasionally occur in the same lesion. Warts generally occur in several sites in infected individuals and more than 60% of patients with partners having condyloma (genital warts) develop lesions, with an average incubation time of 3 months. A range of treatment options are currently available. However, they rely upon excision or ablation and/or the use of topical gels and creams. They are not pain free, they may require frequent clinic visits, and efficacy is highly variable. Disease recurrence remains a significant problem for the effective management of this disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Screening for papilloma viruses Inventor(s): Doorbar, John; (London, GB) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20030175682 Date filed: November 5, 2001
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Abstract: The invention relates to a method of screening for precursor lesions which can lead to cervical malignancy, methods of detecting and typing human papilloma virus infections, and reagents of use in these methods. Excerpt(s): This invention relates to a method of screening for precursor lesions which can lead to cervical malignancy, methods of detecting and typing HPV infections, and reagents of use in the above methods. Studies on naturally-occurring warts have revealed the virus to encode three late proteins--L1 and L2, which are virion coat proteins (Doorbar et al, 1987), and E1{circumflex over ( )}E4, a non-structural late protein of unknown function (Doorbar et al, 1986). In HPV1-induced warts the E1{circumflex over ( )}E4 protein is first expressed in cells of the lower spinous layer, and assembles into distinctive cytoplasmic and nuclear inclusions. During terminal differentiation it is post-transcriptionally modified by phosphorylation (Grand et al, 1989) and by removal of sequences from the N-terminus (Doorbar et al, 1988; Roberts et al, 1994). The E1{circumflex over ( )}E4 proteins of high risk viruses have been poorly characterised, because it has been thought that HPV16-induced lesions contain only small numbers of productively infected cells, and that these contain only low levels of E4 (Doorbar et al, 1996b: Crum et al, 1990). A single Mab (TVG 402) to HPV16 E1{circumflex over ( )}E4 has been used to locate the protein to the cytoplasm but was reported not to work well on paraffin-embedded archival material (Doorbar et al. 1992). Furthermore, polyclonal antibody studies on the E4 proteins of mucosal viruses have yielded conflicting results. One study has supported the above findings (Crum et al, 1990), while another has indicated that the protein is located to the nucleus ( Palefsky et al. 1991). In many countries there are screenig prograrmes to detect the presence of cervical carcinoma at an early stage. Generally such prdgrammes operate by obtaining cervical smears from women potentially at risk of developing cervical cancer, with the resulting smears routinelv beinz examined bv conventional histopathological techniques. These techniques are laborious and time-consuming, require considerable experience to interpret results correctly, and frequently give rise to relatively large percentages of false positive results, causing unnecessary alarm. False negatives can occur when screening is carried out by inexperienced personnel and can lead to the classification of precancerous lesions as normal. There is thus a need for an improved cervical cancer screening method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Skin patch for use in contact immunotherapy Inventor(s): Hopp, Robert B.; (Richland, WA) Correspondence: Stephen R. May; 412 Broadmoor ST; Richland; WA; 99352; US Patent Application Number: 20010051182 Date filed: January 25, 2001 Abstract: A device, preferably in the form of a skin patch, is disclosed for usage in the delivery of a contactant to human skin for the purpose of treating medical conditions responsive to contact immunotherapy, without the presence of medication to alleviate contact dermatitis induced by the contactant. The skin patch specifically induces a cellmediated contact dermatitis in the treatment of skin disorders. Its anticipated use pertains to treatment of, for example, human papilloma virus infections, or warts. In a first embodiment, a pressure activated single chambered skin patch is topically applied and used for controlled release of contactant to human skin. In a second embodiment, a pressure activated two-chambered skin patch is topically applied and used for
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controlled release of a contactant to human skin. Alternatively, a single chambered skin patch is topically applied and hydrated by the contacted skin for release of contactant. In an additional embodiment, the contactant may be applied separately of the skin patch portion, in a manner that maintains the contactant in contact with the patient's skin for the predetermined period of time necessary to cause sufficient contact dermatitis to effect resolution of the medical condition. Excerpt(s): This application is a Continuation n-Part application of co-pending U.S. patent application Ser. No. 09/095,700, which was a Continuation-In-Part application of U.S. patent application Ser. No. 08/717,108 which has now issued as U.S. Pat. No. 5,846,559. This disclosure pertains to a skin patch for delivery of an active contactant that induces a contact dermatitis for treatment of medical conditions responsive to contact immunotherapy. An example of the medical condition treated by the present invention is human papilloma viral infections, more commonly known as warts. While not limited in its specific medical application, the contactant delivery system described herein was developed as an effective means for treating human papilloma viral infections, or warts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Topical pharmaceutical composition for the treatment of warts Inventor(s): Hsu, Tsung-Min; (San Diego, CA), Luo, Eric C.; (Plano, TX), Maibach, Howard I.; (San Francisco, CA) Correspondence: Reed & Eberle Llp; 800 Menlo Avenue, Suite 210; Menlo Park; CA; 94025; US Patent Application Number: 20030072814 Date filed: June 21, 2002 Abstract: Provided is a topical pharmaceutical composition for the treatment of warts, together with methods for its use. The composition and methods involve the topical use of an active agent effective in the treatment of warts plus a permeation-enhancing base that, in one embodiment, gives the composition a pH of about 8.0 to about 13.0, preferably about 8.0 to 11.5, and most preferably about 8.5 to 10.5. This composition can be used to treat human papilloma virus infections, particularly cutaneous warts. Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/972,008 filed on Oct. 4, 2001, which is a continuation in part of U.S. Ser. No. 09/738,410 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/569,889 filed on May 11, 2000, which is a continuation in part of U.S. Ser. No. 09/465,098 filed on Dec. 16, 1999; and is a continuation in part of U.S. Ser. No. 09/738,395 filed on Dec. 14, 2000, which is a continuation in part of U.S. Ser. No. 09/607,892 filed Jun. 30, 2000, now abandoned. This invention relates generally to methods and pharmaceutical formulations for treating warts, particularly cutaneous non-genital warts caused by the human papilloma virus. More particularly, this invention relates to compositions that comprise (a) an active agent useful in the treatment of warts when applied topically, and (b) an agent that enhances the permeability of skin or mucosal tissue to the active agent. Warts are benign protuberances of the skin or mucosa that are caused by the human papilloma virus (HPV). They represent one of the most common skin diseases, affecting approximately 7-12% of the world population. Warts occur most commonly on the hands and feet but can affect nearly any area of skin or mucosal surface. Children are the most commonly afflicted, with the incidence dropping significantly after the age of 25; warts can,
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however, occur at any age. Although rarely medically serious, warts nevertheless are cosmetically disfiguring, and patients will expend considerable time and resources to remove them. Warts on the soles of the feet (plantar warts) can be painful and interfere with walking. Rarely, non-genital HPV infections will induce cancer. 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 human papilloma virus, 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 “human papilloma virus” (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 human papilloma virus. You can also use this procedure to view pending patent applications concerning human papilloma virus. 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 6. BOOKS ON HUMAN PAPILLOMA VIRUS Overview This chapter provides bibliographic book references relating to human papilloma virus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on human papilloma virus 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 “human papilloma virus” (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 human papilloma virus: •
Panel Discussion: Session II Source: Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections. San Diego, CA, January 18-20, 1988. Contact: PSG Publishing Company, 545 Great Rd, Littleton, MA, 01460, (508) 486-8971. Summary: These proceedings of the Conference Perspectives on Oral Manifestations of AIDS: Diagnosis and Management of HIV-Associated Infections held in San Diego, CA, on January 18-20, 1988. They report that more than 70 percent of persons who test positive to antibodies for the Human immunodeficiency virus (HIV) that causes Acquired immunodeficiency syndrome (AIDS) manifest oral lesions. The dentist has not only become the diagnostician of oral diseases associated with HIV, but often assumes primary responsibility for treating oral diseases. Reports document bacterial, fungal, viral, neoplastic, and certain nonspecific lesions occurring in the mouth. Current
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treatment of the most commonly encountered oral mucosal lesions such as candidiasis, herpes, oral hairy leukoplakia, human papilloma virus, and Kaposi's sarcoma is described. Experimental treatment modalities are also discussed. •
Guidelines for Perinatal Care Summary: This monograph lists guidelines for infection control of Human immunodeficiency virus (HIV) and other viral infections in infants, developed by the American Academy of Pediatrics (AAP) Committee on Fetus and Newborn, and the American College of Obstetricians and Gynecologists (ACOG), Committee on Obstetrics: Maternal and Fetal Medicine. It covers clinical and epidemiologic features of HIV infection in women and infants, diagnosis and prevention, and hospital obstetric management of an HIV-infected mother and her infant. Prevention measures for Human papilloma virus and rubella are also included.
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Sexually Transmitted Diseases: Problems in Primary Care Contact: Practice Management Information Corporation, 4727 Wilshire Blvd Ste 300, Los Angeles, CA, 90010, (800) 633-7467. Summary: This monograph provides basic and practical information on sexually transmitted diseases (STDs). It is designed for physicians, particularly those practicing family and emergency medicine. The monograph describes how various STDs are spread and exactly what is meant by safe sexual practices. It covers the many types of venereal disease (VD) currently prevalent, as well as non-VD infections that can be spread by sexual contact. Each chapter deals with one type of disease, or groups of closely related diseases or infections. Methods of recognizing, treating, and preventing each disease are covered. The effectiveness and outcome statistics for treatments are discussed, with effectiveness based on current sensitivities of the infecting organism. The type of the organism and its life cycle are described. Chapters on the "classic" STDs include: gonorrhea, syphilis, lymphogranuloma venereum, and chancroid. Other chapters discuss: HIV infection, herpes simplex, cytomegalovirus (CMV), human papilloma virus (HPV), hepatitis, and chlamydia. The monograph also contains information concerning related topics such as management of rape victims and contraception.
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 “human papilloma virus” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “human papilloma virus” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “human papilloma virus” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Human Papilloma Virus - An Oncogenic Pathogen [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3W3; http://www.amazon.com/exec/obidos/ASIN/B00008R3W3;/icongroupinterna
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The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “human papilloma virus” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
Antibody response against human papilloma viruses Author: Pyrhönen, Seppo.; Year: 2001; Helsinki: [s.n.], 1978; ISBN: 9519918655
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Human papilloma virus infection: a clinical atlas Author: Gross, G. (Gerd); Year: 1997; Berlin: Ullstein Mosby, c1997; ISBN: 3861261170
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Nucleic acid hybridization techniques in diagnosis of human papilloma virus (HPV) infections of the uterine cervix Author: Parkkinen, Sinikka.; Year: 1988; Kuopio: Dept. of Clinical Microbiology, University of Kuopio, 1988; ISBN: 9517802609
Chapters on Human Papilloma Virus In order to find chapters that specifically relate to human papilloma virus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and human papilloma virus 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 “human papilloma virus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on human papilloma virus: •
Global Incidence and Etiology Source: in Close, L.G.; Larson, D.L.; Shah, J.P., eds. Essentials of Head and Neck Oncology. New York, NY: Thieme Medical Publishers, Inc. 1998. p. 3-10. Contact: Available from Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001. (800) 782-3488. Fax (212) 947-1112. Website: www.thieme.com. PRICE: $59.00. ISBN: 0865777403. Summary: This chapter on global incidence and etiology is from a text on cancer of the head and neck. Cancer of the head and neck is a complex disease which, when understood, can often be treated very effectively, rendering the patient disease free while preserving or restoring both form and function. For the purposes of this chapter, the discussion of the etiology and incidence of head and neck cancer will focus on epithelial malignancies of the upper aerodigestive tract, with particular attention to
10
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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squamous cell carcinomas of the oral cavity, pharynx, and larynx. Increased risk is found in men, older age, poor oral hygiene, and low socioeconomic status. Tobacco and alcohol use are independent risk factors for head and neck cancer. Leukoplakia, erythroplakia, and submucous fibrosis are premalignant lesions. Mucosal changes leading to field cancerization are common. Epstein Barr (EB) virus and human papilloma virus are associated with cancers of the nasopharynx and laryngopharynx, respectively. Patients with HIV are at increased risk for head and neck cancer. The authors conclude that the etiology of head and neck cancer is multifactorial. Screening and prevention programs should be encouraged for those patients at increased risk for this disease. The chapter, written by experts in the field, includes a summary of key points and a list of recommended readings. 1 figure. 5 references.
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CHAPTER 7. MULTIMEDIA ON HUMAN PAPILLOMA VIRUS Overview In this chapter, we show you how to keep current on multimedia sources of information on human papilloma virus. 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.
Video Recordings An excellent source of multimedia information on human papilloma virus is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “human papilloma virus” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video 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 “Videorecording (videotape, videocassette, etc.).” Type “human papilloma virus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on human papilloma virus: •
Update: Sexually Transmitted Diseases Contact: Sunburst Technology, 101 Castleton St, Pleasantville, NY, 10507-9971, (800) 4311934, http://www.sunburst.com. Summary: This video and accompanying teacher's guide provides information about sexually transmitted diseases (STDs) and teenagers. The objective is to explain what these diseases are, how they are spread, how to prevent them, and what to do when an infection is suspected. In addition to explaining the health risks associated with these diseases, the video provides information on the emotional turmoil these diseases often bring. The video revolves around true-to-life stories of a number of teenagers who find themselves facing the diagnosis of an STD. The video covers HIV, chlamydia, human papilloma virus, and genital herpes. In addition, the video alerts the viewers to the symptoms of other STDs, including chancroid, hepatitis B, syphilis, and gonorrhea.
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•
Sexually Transmitted Diseases Contact: Milner - Fenwick, Incorporated, 2125 Greenspring Dr, Timonium, MD, 210939989, (410) 252-1700. Summary: This videorecording provides an overview of the most common sexually transmitted diseases (STDs): chlamydia, gonorrhea, human papilloma virus (HPV), herpes, genital warts, and AIDS. It explains who is at risk and describes the symptoms in both men and women. It urges regular medical check-ups and immediate medical care if symptoms are present. Treatments for curable STDs are outlined. The video recommends abstinence but suggests that risk can be reduced with the use of condoms and spermicide.
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 “human papilloma virus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on human papilloma virus: •
Medical Services for HIV+ Women: A Model for Primary Care in a CBO; 15th National Lesbian & Gay Health Conference & 11th Annual AIDS/HIV Forum; Houston, TX, July 20-25, 1993 Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This sound recording contains the transcript of a presentation on the establishment of a model primary care program for women in a community-based organization (CBO). The program described is specifically designed to address HIVpositive women who are asymptomatic or mildly symptomatic. It describes the services available to women through the early intervention program at the Jeffrey Goodman Center in Los Angeles, as well as through the comprehensive women's clinic that was established in response to the increase of HIV disease in women. The clinic aims to be one-stop shopping in health care, and includes services such as gynecology, obstetrics, mammograms, Pap tests, and lab tests for sexually transmitted diseases (STDs). The procedures that a client will receive are outlined, and detailed history and consent procedures are explained. The results of a small study showing a positive correlation between Human papilloma virus and HIV are presented.
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Gyn Manifestations: 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 offers a presentation from the National Conference on Women and AIDS/HIV Infection held December 13-14, 1990, in Washington, D.C., that deals with gynecological manifestations of human immunodeficiency virus (HIV) infection. HIV is the cause of acquired immunodeficiency syndrome (AIDS). The first speaker explains a variety of fungal infections and treatment for them. The second speaker discusses human papilloma virus and its connection with cervical neoplasia.
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Pap smears should be done frequently on women who are HIV positive because of the possible increased risk of cervical cancer. Colposcopy is seen as an increasingly necessary diagnostic tool for such women. The next speaker analyzes the carcinogenicity of Azidothymidine (AZT) in rats and mice. It appears to increase substantially the number of malignant vaginal tumors. The final speaker describes sexually transmitted disease (STD) manifestations in women with HIV.
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CHAPTER 8. PERIODICALS AND NEWS ON HUMAN PAPILLOMA VIRUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover human papilloma virus.
News Services and Press Releases One of the simplest ways of tracking press releases on human papilloma virus 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 “human papilloma virus” (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 human papilloma virus. 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 “human papilloma virus” (or synonyms). The following was recently listed in this archive for human papilloma virus: •
Nearly All Invasive Cervical Cancers Contain Human Papilloma Virus Source: Reuters Medical News Date: June 07, 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. 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 “human papilloma virus” (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 “human papilloma virus” (or synonyms). If you know the name of a company that is relevant to human papilloma virus, 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 “human papilloma virus” (or synonyms).
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Academic Periodicals covering Human Papilloma Virus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to human papilloma virus. In addition to these sources, you can search for articles covering human papilloma virus 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 Institute11: •
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/
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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.12 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:13 •
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
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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
12
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). 13 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 Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “human papilloma virus” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “human papilloma virus” (or synonyms) into the “For these words:” box. The following is a sample result: •
Human Papilloma Virus Contact: National Abstinence Clearinghouse, 801 E 41st St, Sioux Falls, SD, 57105, (888) 577-2966, http://www.abstinence.net. Summary: This brochure, for the general public, provides information about the sexually transmitted disease (STD), the human papillomavirus (HPV). The brochure describes HPV, its transmission, prevention, epidemiological data, and the long-term effects of HPV. It provides a phone number and Web address for individuals to access products and resources on abstinence until marriage.
•
Human Papilloma Virus and Cervical Cancer Issues for Women With HIV and AIDS Contact: Voices of Positive Women, PO Box 471 Ste C, Toronto, (416) 324-8703, http://webhome.idirect.com/~vopw/. Summary: This paper covers basic information about Human Papilloma Virus and cervical cancer, both common opportunistic conditions in women with Acquired immunodeficiency syndrome (AIDS). It looks at diagnostic and treatment procedures for the two conditions, and outlines followup and prevention policies.
The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “human papilloma virus” (or synonyms) into the search box and click “Search.” The
14 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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).
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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 7600 60 441 302 0 8403
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “human papilloma virus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists19 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.20 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.21 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/. 16
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20 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. 21 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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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/.
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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 human papilloma virus 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 human papilloma virus. 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 human papilloma virus. 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 “human papilloma virus”:
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•
Other guides AIDS http://www.nlm.nih.gov/medlineplus/aids.html Cervical Cancer http://www.nlm.nih.gov/medlineplus/cervicalcancer.html HPV http://www.nlm.nih.gov/medlineplus/hpv.html Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Sexually Transmitted Diseases http://www.nlm.nih.gov/medlineplus/sexuallytransmitteddiseases.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 human papilloma virus. 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: •
The Lesbian AIDS Project Information Packet. Translated title Contact: Gay Mens Health Crisis, Lesbian AIDS Project, 119 W 24th St, New York, NY, 10011, (212) 367-1363, http://www.gmhc.org. Summary: The invisibility of lesbian risk for HIV is the main focus of this collection of materials. According to the editors, denial and fear continue to dominate the discussion of HIV transmission among lesbians. The materials include a lesbian sex survey, questions and demands determined at the first meeting of Lesbian, Bisexual Women at the VIII International AIDS Conference in Amsterdam, and various newsletter and journal reprints. They speak to the issues of lesbian risk of HIV, HIV risk among women injecting drug users (IDUs) who have sex with women, the risk of cervical cancer among women with human papilloma virus (HPV), and societal impediments to HIV/AIDS and safer sex education for lesbians. Two articles describing goals and activities of the Gay Men's Health Crisis' Lesbian AIDS Project are provided in both Spanish and English.
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Genital Warts : Sexually Transmitted Disease Contact: Education Training and Research Associates, PO Box 1830, Santa Cruz, CA, 95061-1830, (800) 321-4407, http://www.etr.org. Summary: This brochure for the general public provides information about the symptoms, appearance, diagnosis, and medical treatment of the sexually transmitted disease (STD), genital warts. The brochure describes the human papilloma virus (HPV) that causes the warts and explains the dangers of the disease if it goes untreated. The brochure lists the symptoms of genital warts for both men and women, and provides an overview of the methods used to diagnose the disease. The brochure recommends several preventive measures one can take to avoid contracting genital warts including sexual abstinence, condom use, spermicide use, STD tests, and the avoidance of drugs and alcohol. The brochure offers several suggestions about the medical treatment of genital warts.
•
How to Share Love With Less Risk Contact: Group Health Cooperative, Administrative Center, 5615 W Sunset Hwy, Spokane, WA, 99224, (509) 838-9100, http://www.ghc.org. Summary: This brochure urges teens to set limits for their sexual relationships in order to protect themselves from sexually transmitted diseases (STDs) and pregnancy. The text briefly outlines the dangers of STDs; including HIV/AIDS, herpes, human papilloma virus (HPV), chlamydia, and gonorrhea. The brochure indicates sexual abstinence is the only totally safe choice, but promotes the use of condoms and spermicides for sexual activity. It emphasizes that acting responsibly is a way of expressing caring and love.
•
Anal Warts: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. 2 p. Contact: Available from American Society of Colon and Rectal Surgeons. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 2909184. Fax (847) 290-9203. Price: Single copy free; bulk copies available. Summary: This brochure, from the American Society of Colon and Rectal Surgeons, provides basic information about anal warts (condyloma acuminata). Anal warts are thought to be caused by the human papilloma virus. The brochure provides information on the symptoms and treatment of anal warts. The brochure notes that if the warts are not removed, the warts generally grow larger and become more and more numerous. In addition, there is evidence that these warts can become cancerous if left untreated for a long time. Treatment options include medications, electrical cautery, laser surgery, and surgical removal. The cautery and excision technique can be performed on an outpatient basis, and the patient can go home after the procedure. Most people are moderately uncomfortable for a few days after treatment, and pain medication may be prescribed. Depending on the extent of the disease, some people return to work the next day, while others may remain out of work for several days. The brochure provides tips to avoid recurrence and reinfection, including: continue observation for several months, and abstain from sexual contact with individuals who have anal (or genital) warts. The brochure concludes with a brief description of the specialty practiced by colon and rectal surgeons. 1 figure. (AA-M).
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Young People and STDs/HIV/AIDS : Part I : Dimensions of the Problem Contact: Pathfinder International, 9 Galen St Ste 217, Watertown, MA, 02472-4501, (617) 924-7200, http://www.pathfind.org. Summary: This fact sheet presents information about young people and sexually transmitted diseases (STD) and the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). The fact sheet examines the current epidemiology of STDs and HIV/AIDS among adolescents and young adults around the world, particularly in developing nations. It identifies biological, behavioral, and cultural factors that place young people at such high risks of contracting STDs and HIV. Specific factors discussed include young age at first intercourse, immature reproductive and immune systems, inability to refuse sex or insist on protection, poverty, homelessness, lack of health education, and inadequate health services. The fact sheet also discusses health and social consequences of high STD rates among young people. Specific consequences discussed include pelvic inflammatory disease (PID), genital human papilloma virus (HPV), negative pregnancy outcomes, increased risk of HIV infection, psychological consequences, and infertility.
•
Guidelines for the Management of Gynecologic Infections Contact: Project Inform, HIV Treatment Hotline, 205 13th St Ste 2001, San Francisco, CA, 94103, (415) 558-8669, http://www.projectinform.org. Summary: This fact sheet uses a chart format to present guidelines for the management of gynecologic infections in women with HIV/AIDS. The infections discussed include: chancroid, chlamydia, gonorrhea, herpes simplex virus, genital warts [ human papilloma virus (HPV)], syphilis, and vaginal candidiasis. It outlines symptoms, diagnostic procedures, treatment, prophylaxis and maintenance options, possible side effects from treatment, and drug interactions.
•
Human Papillomavirus (HPV) Contact: University of New Mexico School of Medicine, New Mexico AIDS Education and Training Center, New Mexico AIDS InfoNet, PO Box 810, Arroyo Seco, NM, 87514, (505) 776-8032, http://www.aidsinfonet.org. Summary: This information sheet discusses human papilloma viruses (HPVs), common viruses that can cause warts or abnormal cell growth called dysplasia. HPV is transmitted by direct contact with infected areas such as during sexual activity. Some HPVs cause warts of the hands or feet, others cause genital warts or anal warts or dysplasia, which can develop into cervical or anal cancer. HPVs are common in women with human immunodeficiency syndrome (HIV) and in some HIV positive men. The information sheet explains the different types of HPV, their transmission, detection, and treatment. Immediate treatment is recommended to prevent spread of the disease.
•
Human Papillomavirus Testing.: Improving Cervical Cancer Screening: What You Need to Know Contact: Digene Corporation, 1201 Clopper Rd, Gaithersburg, MD, 20878, (301) 9447000, http://www.digene.com. Summary: This pamphlet discusses the sexually transmitted disease (STD) human papilloma virus (HPV), which is the leading cause of cervical cancer. The pamphlet explains the signs of HPV infection in the form of bumps called genital warts, transmission, testing, and prevention. A new test called the Hybrid Capture HPV DNA
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Assay can indicate the presence and type of HPV. The use of latex condoms may reduce the risk of HPV, however the virus can be spread from warts in areas not covered by the condom. •
Sexually Transmitted Infections: The Facts Contact: Planned Parenthood Federation of America Incorporated, PO Box 4457, New York, NY, 10163-4457, (800) 669-0156, http://www.plannedparenthood.org. Summary: This pamphlet provided facts about sexually transmitted diseases (STDs). For each of the several STDs discussed, the pamphlet outlines symptoms, diagnostic methods, treatments, possible long-term effects, tranmission, and prevention. Specifically, the pamphlet provides information on bacterial vaginosis, chlamydia, cytomegalovirus (CMV), gonorrhea, hepatitis, herpes, human immunodeficiency virus (HIV), human papilloma virus (HPV), molluscum contagiosum, pelvic inflammatory disease (PID), public lice, scabies, syphilis, trichomoniasis, and urinary tract infections.
•
Genital Warts : Questions and Answers Contact: Planned Parenthood of Federation of America Incorporated, PO Box 4457, New York, NY, 10163-4457, (800) 669-0156, http://www.plannedparenthood.org. Summary: This pamphlet provides information on a strain of the sexually transmitted disease (STD), the human papilloma virus (HPV) that causes genital warts. It provides information on its transmission, treatment, prevention, diagnosis, symptoms, and what pregnant women can do to avoid transmitting this STD to their infants.
•
Genital Warts Source: Schaumburg, IL: American Academy of Dermatology (AAD). 2001. 6 p. Contact: Available from American Academy of Dermatology, Marketing Department. P.O. Box 2289, Carol Stream, IL 60132-2289. (847) 240-1280. Fax (847) 240-1859. E-mail:
[email protected]. Website: www.aad.org. PRICE: Single copy free; bulk prices available. Summary: This pamphlet uses a question and answer format to provide people who have genital warts with information on the etiology, symptoms, and treatment of this condition. Genital warts, also known as venereal warts, are caused by the human papilloma virus (HPV). They are usually sexually transmitted, but they can transmitted to infants who have been delivered vaginally by mothers with HPV in their genital tract. These warts are a problem in pregnant women and in people whose immune system has been compromised. Warts can be rough or smooth surfaced, large or small, and are usually flesh colored. Diagnosis is usually based on simple visual inspection by the doctor. The type of treatment selected depends on the number of warts, their specific location, and other factors. Treatment options include surgical excision, removal with an electric needle, freezing, or laser excision. Chemicals may also be used to remove warts, including acids, 5-fluorouracil cream, and podophyllin. These surgical and chemical treatments do not affect the underlying HPV, so the warts may recur. Two new treatments that have become available are podofilox gel and imiquimod cream. The former medication stops the growth of the wart cells, while the latter medication induces the body to produce proteins that act against the HPV and boost the immune system locally. One of the most promising new areas being investigated for the treatment and prevention of genital warts is HPV vaccines. 3 figures.
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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 located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Venereal (Genital) Warts Summary: Answers to common questions and concerns from consumers on venereal (genital) warts, a sexually transmitted disease. These warts are known to be caused the Human Papilloma Virus (HPV). Source: NOAH: New York Online Access to Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2213 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 human papilloma virus. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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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 human papilloma virus. By consulting all of
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associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with human papilloma virus. 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 human papilloma virus. 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 “human papilloma virus” (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 “human papilloma virus”. 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 “human papilloma virus” (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 “human papilloma virus” (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.22
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
22
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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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/
23
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
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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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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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).
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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HUMAN PAPILLOMA VIRUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Ablation: The removal of an organ by surgery. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [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] 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] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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
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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 preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Alpha-helix: One of the secondary element of protein. [NIH] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [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 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] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH]
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Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [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] 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] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid 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] Anionic: Pertaining to or containing an anion. [EU] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anogenital: Pertaining to the anus and external genitals. [EU] 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] Antiallergic: Counteracting allergy or allergic conditions. [EU] 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]
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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] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [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-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphonia: Complete loss of phonation due to organic disease of the larynx or to nonorganic (i.e., psychogenic) causes. [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] Aqueous: Having to do with water. [NIH]
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Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] 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] 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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Avian: A plasmodial infection in birds. [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] Bacterial Physiology: Physiological processes and activities of bacteria. [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] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form
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salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [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] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [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] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [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
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clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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]
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 Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [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] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] 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] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Calcium: A basic element found in nearly all organized tissues. It is a member of the
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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 many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [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]
Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
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] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [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] 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] 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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after
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treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] 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 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 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 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 Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [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] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [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] Cervix Dysplasia: A spectrum of histologic changes in the epithelium of the cervix uteri which may begin as a superficial lesion and progress to invasive carcinoma. [NIH] Chancroid: Acute, localized autoinoculable infectious disease usually acquired through
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sexual contact. Caused by Haemophilus ducreyi, it occurs endemically almost worldwide, especially in tropical and subtropical countries and more commonly in seaports and urban areas than in rural areas. [NIH] Check-up: A general physical examination. [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] 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] 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] 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] 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] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] 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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU]
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Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [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] 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] Communicable disease: A disease that can be transmitted by contact between persons. [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 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
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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] 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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Condylomata Acuminata: Sexually transmitted form of anogenital warty growth caused by the human papillomaviruses. [NIH] 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] Cone biopsy: Surgery to remove a cone-shaped piece of tissue from the cervix and cervical canal. Cone biopsy may be used to diagnose or treat a cervical condition. Also called conization. [NIH] Conization: The excision of a cone of tissue, especially of the cervix uteri. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constriction: The act of constricting. [NIH]
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Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [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] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] 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] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cruciferous vegetables: A family of vegetables that includes kale, collard greens, broccoli, cauliflower, cabbage, brussels sprouts, and turnip. These vegetables contain substances that
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may protect against cancer. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Cryptococcus: A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium. [NIH]
Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH]
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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] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [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] Dermatitis: Any inflammation of the skin. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis
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orientalis L. and Digitalis lanata Ehrh. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [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] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] 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 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] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [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] Ductal carcinoma in situ: DCIS. Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called intraductal carcinoma. [NIH] Duodenum: The first part of the small intestine. [NIH]
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Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]
Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dysplastic nevi: Atypical moles; moles whose appearance is different from that of common moles. Dysplastic nevi are generally larger than ordinary moles and have irregular and indistinct borders. Their color frequently is not uniform and ranges from pink to dark brown; they usually are flat, but parts may be raised above the skin surface. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [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 based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH]
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Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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] 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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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] 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] 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] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH]
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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] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] 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] Epidermodysplasia Verruciformis: An autosomal recessive trait with impaired cellmediated immunity. About 15 human papillomaviruses are implicated in associated infection, four of which lead to skin neoplasms. The disease begins in childhood with red papules and later spreads over the body as gray or yellow scales. [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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]
Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may
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result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroplakia: A reddened patch with a velvety surface found in the mouth. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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 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]
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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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [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] 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 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] 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
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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] 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] Fovea: The central part of the macula that provides the sharpest vision. [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] 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] 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] 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]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH]
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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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [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 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 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] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] 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] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [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] Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related Cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans. [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]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when
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cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] 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] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] 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] Grafting: The operation of transfer of tissue from one site to another. [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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Gynaecological: Pertaining to gynaecology. [EU] 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] Hair Color: Color of hair or fur. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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]
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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] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [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] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [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 virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH]
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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]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospital Records: Compilations of data on hospital activities and programs; excludes patient medical records. [NIH] Host: Any animal that receives a transplanted graft. [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] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [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] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]
Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH]
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Hygienic: Pertaining to hygiene, or conducive to health. [EU] 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] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [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 Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [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]
Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. [NIH]
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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] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] 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] Incision: A cut made in the body during surgery. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] 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,
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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]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] 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] 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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] 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] 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 Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [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] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell
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activity. [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] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] 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] Intracellular: Inside a cell. [NIH] Intradermal Tests: Skin tests in which the sensitizer is injected. [NIH] Intraductal carcinoma: Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called ductal carcinoma in situ. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [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] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] 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] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] 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]
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Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keratosis: Any horny growth such as a wart or callus. [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] 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] 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] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [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] Lentigo: Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The
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granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or 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] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligase Chain Reaction: A DNA amplification technique based upon the ligation of oligonucleotide probes. The probes are designed to exactly match two adjacent sequences of a specific target DNA. The chain reaction is repeated in three steps in the presence of excess probe: (1) heat denaturation of double-stranded DNA, (2) annealing of probes to target DNA, and (3) joining of the probes by thermostable DNA ligase. After the reaction is repeated for 20-30 cycles the production of ligated probe is measured. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]
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Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] 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]
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 Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphoepithelioma: A type of cancer that begins in the tissues covering the nasopharynx (the upper part of the throat behind the nose). [NIH] Lymphogranuloma Venereum: Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. but is more widespread in developing countries. It is distinguished from granuloma venereum (granuloma inguinale), which is caused by Calymmatobacterium granulomatis. [NIH]
Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH]
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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] 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 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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [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
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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] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Membrane: A very thin layer of tissue that covers a surface. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Mesothelial: It lines the peritonealla and pleural cavities. [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] 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] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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
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organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [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] Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Mode of Transmission: Hepatitis A [NIH] 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] 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 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] 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] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucopurulent: Containing both mucus and pus. [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] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous
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chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] 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] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] 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] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [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] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Nonoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Nonoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide,
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formulated primarily as a component of vaginal foams and creams. [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] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [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 next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as complexes called nucleoproteins. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Octamer: Eight molecules of histone. [NIH] 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] Odour: A volatile emanation that is perceived by the sense of smell. [EU] 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] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label
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biotin. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [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 oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [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] Oropharynx: Oral part of the pharynx. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [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] 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
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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]
P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [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 Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] 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] 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] 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] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [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 (= 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]
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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] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Pelvic inflammatory disease: A bacteriological disease sometimes associated with intrauterine device (IUD) usage. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [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] 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] Perianal: Located around the anus. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH]
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Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] 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] Phonation: The process of producing vocal sounds by means of vocal cords vibrating in an expiratory blast of air. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [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] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photofrin: A drug used in photodynamic therapy that is absorbed by tumor cells; when absorbed by cancer cells and exposed to light, it 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] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plant Viruses: Viruses parasitic on plants higher than bacteria. [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] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [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] 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]
Pleated: Particular three-dimensional pattern of amyloidoses. [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] Podophyllin: Caustic extract from the roots of Podophyllum peltatum and P. emodi. It contains podophyllotoxin and its congeners and is very irritating to mucous membranes and skin. Podophyllin is a violent purgative that may cause CNS damage and teratogenesis. It is used as a paint for warts, skin neoplasms, and senile keratoses. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [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 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
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analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [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] 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] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] 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] 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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of
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strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU]
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Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] 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 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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [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 p53: Nuclear phosphoprotein encoded by the p53 gene whose normal function is to control cell proliferation. A mutant or absent p53 protein has been found in leukemia, osteosarcoma, lung cancer, and colorectal cancer. [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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
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-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH]
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Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [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 treatment of mental disorders. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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] 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]
Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons,
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alpha particles) or a mixture of these. The most common source is the sun. [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] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] Rape: Unlawful sexual intercourse without consent of the victim. [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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] 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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH]
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Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [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] 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 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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [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] 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] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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 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] Retinal Neovascularization: Formation of new blood vessels originating from the retinal
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veins and extending along the inner (vitreal) surface of the retina. [NIH] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]
Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] 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] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] 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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rotavirus Vaccines: Vaccines or candidate vaccines used to prevent infection with rotavirus. [NIH] Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory
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tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Rubella Virus: The type (and only) species of Rubivirus causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis. [NIH] Safe Sex: Sex behavior that prevents or decreases the spread of sexually transmitted diseases or pregnancy. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]
Schistosome: Dermatitis caused by the snail parasite, Schistosoma cercariae. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [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] 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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH]
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Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [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 Education: Education which increases the knowledge of the functional, structural, and behavioral aspects of human reproduction. [NIH] Sexual Abstinence: Refraining from sexual intercourse. [NIH] Sexual Partners: Married or single individuals who share sexual relations. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin Neoplasms: Tumors or cancer of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels.
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[NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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 Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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 mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [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] 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] 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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes.
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Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermicide: An agent that is destructive to spermatozoa. [EU] 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] Spindle-cell: A fusiforme or spindle-shaped cell, such as a fibroblast. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] 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]
Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] 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]
Standardize: To compare with or conform to a standard; to establish standards. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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]
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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] 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] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [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] 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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submucous: Occurring beneath the mucosa or a mucous membrane. [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] Substrate: A substance upon which an enzyme acts. [EU] Sulfates: Inorganic salts of sulfuric acid. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH]
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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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] Synchrotron: An accelerator in which the particles are guided by an increasing magnetic field while they are accelerated several times in an approximately circular path by electric fields produced by a high-frequency generator. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [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] 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] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Teniposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [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,
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which helps regulate growth and metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [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] 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] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [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] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell
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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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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 (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be 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] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urethritis: Inflammation of the urethra. [EU] 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] 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] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU]
Dictionary 225
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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [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] 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] 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] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verruca: A circumscribed, cutaneous excrescence having a papilliferous surface; a small, circumscribed, epidermal tumor. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia virus and varicella zoster virus. [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] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor
226 Human Papilloma Virus
cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [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] 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] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [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] 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 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
Dictionary 227
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] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Yellow Fever Virus: The type species of the Flavivirus genus. Principal vector transmission to humans is by Aedes spp. mosquitoes. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [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]
229
INDEX A Abdomen, 167, 173, 183, 190, 196, 198, 200, 201, 220, 221, 226 Ablation, 103, 106, 126, 167 Absolute risk, 24, 167 Acquired Immunodeficiency Syndrome, 119, 167 Actin, 65, 167 Acute leukemia, 117, 167 Adaptability, 167, 175 Adaptation, 12, 167 Adenocarcinoma, 14, 33, 56, 57, 167 Adenosine, 167, 208 Adenovirus, 10, 18, 19, 105, 125, 167, 216 Adjustment, 167 Adjuvant, 10, 107, 108, 167, 188 Adrenal Cortex, 167, 179 Adverse Effect, 167, 218 Affinity, 109, 167, 168, 171, 219 Affinity Chromatography, 109, 168 Agar, 168, 209 Airway, 18, 168 Algorithms, 4, 168, 172 Allogeneic, 5, 168, 190, 191 Allograft, 42, 168 Alpha Particles, 168, 214 Alpha-helix, 168, 197 Alphavirus, 13, 168, 218 Alternative medicine, 140, 168 Aluminum, 107, 108, 168 Ameloblastoma, 32, 168 Amino Acid Sequence, 9, 123, 124, 126, 168, 170, 178, 189 Amino Acids, 105, 108, 123, 168, 177, 178, 189, 205, 207, 210, 212, 216, 218, 223 Amino-terminal, 105, 168 Amplification, 20, 33, 103, 104, 110, 111, 113, 169, 198 Anaerobic, 169, 225 Anaesthesia, 169, 194 Anal, 22, 34, 38, 84, 153, 154, 169, 185, 187, 199 Analog, 169, 188 Analogous, 12, 169, 182, 223 Anaphylatoxins, 169, 177 Anatomical, 96, 169, 184, 194 Androgens, 167, 169, 179 Anesthesia, 168, 169
Angiogenesis, 24, 27, 169, 200 Angiogenesis inhibitor, 28, 169 Animal model, 9, 16, 21, 97, 169, 224 Anionic, 119, 169, 219 Annealing, 169, 198, 209 Anogenital, 32, 34, 57, 80, 88, 104, 113, 118, 122, 123, 169, 178, 190 Anoscopy, 23, 169 Antiallergic, 169, 179 Antibacterial, 169, 219 Antibiotic, 169, 219, 225 Antibodies, 8, 26, 39, 97, 99, 102, 106, 124, 131, 170, 190, 193, 194, 199, 209, 214 Anticarcinogenic, 121, 170 Anticoagulant, 170, 212 Antigen-Antibody Complex, 170, 177 Antigen-presenting cell, 170, 181 Anti-inflammatory, 170, 179, 189, 206 Anti-Inflammatory Agents, 170, 179 Antimetabolite, 170, 173, 188 Antineoplastic, 170, 173, 179, 188, 195, 206, 209, 225 Antioxidant, 7, 170 Antiviral, 59, 102, 103, 106, 170, 173, 195, 207, 225 Anus, 169, 170, 207, 214 Aphonia, 18, 170 Apoptosis, 11, 19, 24, 25, 30, 58, 72, 81, 83, 84, 86, 88, 100, 170, 175 Aqueous, 117, 170, 172, 180, 184, 197, 219 Arachidonic Acid, 171, 211 Arginine, 169, 171, 195 Aromatic, 46, 171 Arterial, 171, 212 Arteries, 171, 173, 179, 201 Arterioles, 171, 173 Asbestos, 171, 200, 201 Assay, 5, 11, 14, 17, 20, 98, 102, 104, 111, 155, 171, 193 Astrocytes, 76, 171 Asymptomatic, 22, 98, 122, 136, 171 Attenuated, 97, 124, 171, 217 Atypical, 35, 59, 171, 183 Autologous, 171, 191 Autologous bone marrow transplantation, 171, 191 Avian, 96, 171
230 Human Papilloma Virus
B Bacteria, 12, 108, 124, 125, 169, 170, 171, 183, 187, 190, 201, 204, 208, 219, 223, 224, 225 Bacterial Physiology, 167, 171 Bacteriophage, 171, 209, 223 Basal cell carcinoma, 101, 171 Basal cells, 24, 171, 203 Base, 17, 23, 105, 107, 114, 128, 171, 181, 189, 196, 204, 222 Basement Membrane, 17, 172, 174, 186, 197 Benign tumor, 112, 172, 187 Bile, 172, 192, 198 Binding Sites, 26, 105, 107, 108, 172 Bioavailability, 118, 172 Biochemical, 19, 29, 56, 68, 170, 172, 187 Biological response modifier, 172, 195 Biomarkers, 7, 59, 172 Biopsy, 7, 23, 28, 32, 36, 39, 42, 53, 70, 99, 172, 178 Biopsy specimen, 28, 32, 36, 39, 42, 53, 172 Biosynthesis, 171, 172, 212, 218 Biotechnology, 30, 31, 71, 133, 140, 147, 172 Biotin, 20, 36, 80, 172, 205 Biotransformation, 172 Bladder, 48, 53, 74, 75, 173, 212, 215, 223, 224 Blastocyst, 173, 178, 183 Blood Coagulation, 109, 173, 174, 222 Blood Coagulation Factors, 173 Blood pressure, 173, 202, 219 Blood vessel, 27, 169, 173, 184, 199, 201, 207, 208, 215, 218, 219, 221, 222, 225 Blot, 39, 50, 113, 173, 204 Body Fluids, 172, 173, 182, 219, 224 Bone Marrow, 61, 65, 100, 167, 171, 173, 191, 193, 199, 200, 219, 220, 221 Bone Marrow Cells, 65, 173, 200 Bowel, 169, 173, 196 Brachytherapy, 88, 173, 196, 214, 226 Branch, 163, 173, 180, 183, 199, 206, 213, 219, 222 Breakdown, 173, 181, 188 Bromodeoxyuridine, 20, 173 Bronchi, 173, 223 Bronchial, 73, 173 Bronchus, 67, 70, 173 Buffers, 107, 173 C Calcium, 171, 173, 177, 200, 212, 218
Callus, 174, 197 Cancer vaccine, 20, 27, 174 Candidiasis, 3, 98, 132, 154, 174 Candidosis, 174 Capsid, 26, 97, 108, 174, 226 Carbohydrate, 174, 179, 210 Carbon Dioxide, 174, 187, 215 Carboxy, 109, 174 Carboxy-terminal, 109, 174 Carcinogen, 17, 115, 174 Carcinogenesis, 6, 21, 51, 73, 87, 111, 116, 174 Carcinogenic, 13, 174, 195, 205, 211, 224 Carcinoma in Situ, 31, 76, 96, 104, 105, 174 Carotene, 174, 215 Case report, 36, 67, 75, 174, 176 Case series, 36, 174, 176 Caspase, 76, 175 Causal, 14, 175, 185 Cell, 4, 5, 8, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 25, 26, 27, 28, 29, 30, 33, 35, 36, 43, 44, 48, 49, 54, 55, 56, 60, 63, 65, 67, 71, 73, 74, 75, 76, 83, 84, 87, 88, 96, 99, 100, 101, 102, 104, 108, 111, 115, 116, 118, 121, 124, 127, 154, 167, 169, 170, 171, 172, 173, 174, 175, 176, 177, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 193, 195, 196, 197, 198, 200, 201, 202, 203, 205, 208, 210, 211, 212, 213, 214, 215, 216, 218, 220, 221, 222, 223, 225, 226 Cell Cycle, 11, 13, 175, 176, 180, 186, 211, 213, 222 Cell Death, 100, 170, 175, 186, 203, 222 Cell Differentiation, 121, 175, 218 Cell Division, 171, 175, 180, 186, 196, 200, 202, 208, 211 Cell membrane, 26, 175, 181, 208 Cell proliferation, 175, 212, 216, 218 Cell Size, 175, 187 Cell Transplantation, 8, 175 Cellulose, 175, 188, 208 Central Nervous System, 175, 189, 191, 205 Centrosome, 14, 175, 202 Cervix Dysplasia, 15, 175 Chancroid, 132, 135, 154, 175 Check-up, 136, 176 Chemotactic Factors, 176, 177 Chemotherapy, 8, 9, 19, 27, 85, 86, 100, 103, 176
Index 231
Chlamydia, 23, 35, 49, 69, 98, 132, 135, 136, 153, 154, 155, 176, 190, 199 Choroid, 176, 215 Chromatin, 118, 170, 176, 204, 220 Chromosomal, 29, 54, 169, 176, 216, 217 Chromosome, 33, 38, 50, 64, 176, 190, 217, 223 Chronic, 22, 29, 176, 182, 195, 197, 199, 213, 221, 226 Chronic Disease, 22, 176 CIS, 14, 23, 108, 176, 215 Cisplatin, 86, 103, 117, 176 Clinical Medicine, 176, 210 Clinical study, 85, 176 Clinical trial, 5, 6, 9, 15, 21, 25, 27, 107, 108, 147, 176, 212, 214 Cloning, 5, 38, 60, 106, 172, 176, 198 Coagulation, 39, 173, 176, 197 Codon, 63, 66, 126, 177, 189 Cofactor, 6, 177, 212, 222 Cohort Studies, 177, 185 Collagen, 172, 177, 186, 187, 188, 200, 209, 211 Colorectal, 177, 212 Colorectal Cancer, 177, 212 Colposcopy, 37, 39, 43, 99, 137, 177 Communicable disease, 119, 177 Complement, 112, 169, 177, 178, 189, 200 Complementary and alternative medicine, 83, 91, 177 Complementary medicine, 83, 178 Computational Biology, 147, 178 Conception, 74, 178, 179, 187, 210, 219, 221 Concomitant, 59, 178 Condoms, 136, 153, 155, 178 Condyloma, 39, 41, 54, 84, 100, 104, 113, 120, 126, 153, 178 Condylomata Acuminata, 71, 88, 96, 178 Cone, 54, 178 Cone biopsy, 54, 178 Conization, 178 Conjunctiva, 178, 195 Connective Tissue, 173, 177, 178, 187, 188, 199, 201, 207, 216, 217, 221 Consensus Sequence, 178 Conserved Sequence, 105, 178 Constriction, 178, 217 Consumption, 179, 181, 188, 204, 215 Contact dermatitis, 127, 128, 179 Contamination, 115, 179, 216 Contraception, 132, 179 Contraceptive, 115, 179
Contraindications, ii, 179 Coordination, 88, 179 Cornea, 42, 179, 197, 227 Corneum, 179, 185 Coronary, 179, 201 Coronary Thrombosis, 179, 201 Corpus, 179, 207 Corticosteroid, 109, 179 Cost Savings, 16, 179 Cowpox, 179, 225 Cowpox Virus, 179, 225 Cross-Sectional Studies, 179, 185 Cruciferous vegetables, 120, 179 Cryotherapy, 40, 46, 180 Cryptococcus, 17, 180 Crystallization, 26, 180 Curative, 180, 222 Cutaneous, 12, 28, 36, 40, 48, 55, 69, 106, 120, 122, 126, 128, 174, 179, 180, 196, 217, 225 Cyclic, 105, 180, 208, 211 Cyclin, 13, 58, 59, 180 Cysteine, 123, 180, 184 Cystine, 180 Cytogenetics, 40, 58, 76, 180, 217 Cytokine, 10, 17, 40, 59, 180, 207 Cytomegalovirus, 17, 35, 132, 155, 180 Cytoplasm, 127, 170, 175, 180, 184, 190, 216 Cytotoxic, 14, 21, 30, 103, 124, 180, 214, 218 Cytotoxicity, 27, 100, 176, 180 D Databases, Bibliographic, 147, 180 Decision Making, 4, 180 Degenerative, 180, 191, 199, 216 Deletion, 170, 180 Dementia, 167, 180 Denaturation, 112, 181, 198, 209 Dendrites, 181 Dendritic, 8, 10, 16, 27, 181, 200 Dendritic cell, 8, 10, 16, 27, 181 Density, 181, 187, 198, 209, 219 Dentists, 35, 181 Deoxyribonucleic, 39, 96, 181 Deoxyribonucleic acid, 39, 96, 181 Deoxyribonucleotides, 181 Depolarization, 76, 181, 218 Dermatitis, 127, 181, 217 Detergents, 181, 203 Developing Countries, 181, 199 Diabetes Mellitus, 181, 191
232 Human Papilloma Virus
Diabetic Retinopathy, 28, 181, 208 Diagnostic Imaging, 8, 181 Diagnostic procedure, 95, 140, 154, 181 Diarrhea, 26, 119, 181 Diathermy, 47, 181 Digestion, 121, 172, 173, 181, 196, 198, 221 Digestive tract, 181, 218, 220 Digoxigenin, 20, 42, 181 Dihydroxy, 182, 186 Dilatation, 182, 210 Dimethyl, 17, 182 Diploid, 105, 182, 209 Direct, iii, 8, 11, 16, 20, 23, 109, 112, 154, 176, 182, 214 Discrimination, 4, 182 Disease Progression, 18, 182, 225 Dissection, 4, 182 Dissociation, 167, 182 Distal, 182, 213 Drug Design, 26, 182 Drug Interactions, 154, 182 Drug Resistance, 103, 182 Drug Tolerance, 182 Duct, 182, 196, 217 Ductal carcinoma in situ, 14, 182, 196 Duodenum, 172, 182, 206, 221 Dysentery, 119, 183 Dysphonia, 18, 183 Dysplasia, 4, 14, 15, 17, 31, 73, 90, 98, 102, 154, 183 Dysplastic nevi, 16, 183 Dystrophy, 54, 183 E Edema, 179, 181, 183 Effector, 11, 177, 183, 208 Efficacy, 6, 9, 10, 21, 24, 46, 86, 102, 114, 126, 182, 183 Ejaculation, 183, 217 Elective, 68, 183 Electrocoagulation, 176, 183 Electrolyte, 179, 183, 202, 219 Electrons, 170, 172, 183, 196, 206, 213, 214 Emaciation, 167, 183 Embryo, 84, 173, 175, 183, 194, 210, 220 Embryo Transfer, 183, 210 Emergency Medicine, 132, 183 Emergency Treatment, 183 Empirical, 99, 184 Emulsion, 184, 187 Enamel, 168, 184, 197 Endocarditis, 174, 184 Endocrinology, 45, 184, 190
Endometrial, 42, 67, 184 Endometrium, 52, 184 Endopeptidases, 184, 212 Endoscope, 177, 184 Endothelial cell, 12, 28, 49, 60, 85, 184, 222 Endothelium, 12, 27, 184 Endothelium, Lymphatic, 184 Endothelium, Vascular, 184 Endotoxins, 177, 184 Enhancer, 107, 110, 184 Environmental Exposure, 184, 205 Environmental Health, 146, 148, 185 Enzymatic, 174, 177, 185, 209, 215 Enzyme-Linked Immunosorbent Assay, 102, 185 Epidemic, 22, 185, 220 Epidemiologic Studies, 7, 123, 185 Epidemiological, 4, 16, 22, 51, 110, 117, 148, 185 Epidermal, 46, 51, 58, 100, 185, 197, 200, 225 Epidermal Growth Factor, 46, 51, 58, 185 Epidermis, 17, 24, 101, 171, 179, 185, 192, 197, 210 Epidermodysplasia Verruciformis, 32, 60, 62, 185 Epidermoid carcinoma, 185, 220 Epithelial Cells, 19, 30, 59, 64, 72, 81, 84, 89, 103, 107, 185, 191, 197 Epithelium, 18, 24, 55, 59, 80, 115, 123, 172, 175, 178, 184, 185, 206, 227 Epitope, 116, 124, 185 Erectile, 185, 207 Erythema, 179, 185 Erythrocytes, 173, 186 Erythroplakia, 134, 186 Esophageal, 31, 44, 46, 47, 68, 73, 83, 186 Esophagus, 71, 181, 186, 208, 220, 221 Estrogen, 32, 186 Ethnic Groups, 15, 186 Ethylene Glycol, 114, 186 Etoposide, 117, 186 Eukaryotic Cells, 186, 194, 205, 224 Excitation, 186, 187 Excitatory, 186, 189 Exogenous, 75, 172, 186 Extensor, 186, 213 External-beam radiation, 186, 196, 214, 226 Extracellular, 171, 178, 186, 187, 200, 219 Extracellular Matrix, 178, 186, 187, 200 Extracellular Matrix Proteins, 186, 200
Index 233
Eye Infections, 167, 187 F Family Planning, 4, 147, 187 Farnesyl, 20, 187 Fat, 114, 171, 173, 174, 179, 187, 198, 210, 216, 219, 221 Fatty acids, 187, 211 Fertilization in Vitro, 187, 210 Fetus, 132, 187, 193, 210, 220, 221, 225 Fibrin, 173, 187, 222 Fibrinogen, 187, 222 Fibroblasts, 38, 53, 71, 105, 187 Fibroma, 55, 187 Fibrosis, 100, 134, 187 Fixation, 31, 187 Flow Cytometry, 17, 34, 187 Fluorescence, 69, 98, 187, 188 Fluorescent Dyes, 187, 188 Fluorouracil, 155, 188 Fold, 16, 188 Fovea, 187, 188 Fungi, 12, 187, 188, 201, 227 Fungus, 174, 188 G Gamma Rays, 188, 203, 214 Gas, 174, 188, 192, 203 Gastric, 185, 188 Gastrin, 188, 192 Gastroenteritis, 188, 216 Gastrointestinal, 46, 100, 171, 188, 221, 224 Gastrointestinal tract, 188, 221, 224 Gelatin, 188, 189, 222 Gels, 126, 188 Gene Expression, 17, 18, 40, 45, 54, 72, 83, 84, 111, 119, 189 Generator, 189, 222 Genetic Code, 189, 204 Genetic Engineering, 112, 172, 176, 189 Genetic testing, 189, 210 Genetics, 8, 25, 40, 58, 75, 76, 81, 107, 110, 180, 189 Genital, 4, 10, 22, 24, 25, 28, 36, 38, 39, 42, 46, 47, 49, 50, 60, 65, 66, 70, 73, 80, 85, 86, 87, 89, 96, 97, 99, 101, 104, 106, 107, 108, 109, 112, 115, 116, 119, 120, 122, 123, 126, 128, 135, 136, 153, 154, 155, 156, 189, 190, 224, 226 Genitourinary, 37, 43, 85, 106, 189, 224 Genotype, 104, 110, 126, 189, 208 Germ Cells, 189, 200, 205, 219 Gestation, 189, 207, 220
Gland, 167, 189, 199, 206, 208, 212, 217, 221, 222 Glucocorticoid, 45, 50, 189 Glucose, 175, 181, 189, 191, 195 Glucosinolates, 121, 189 Glutamate, 189 Glutamic Acid, 9, 123, 189, 211 Glycine, 189, 218 Glycogen, 176, 189 Gonorrhea, 4, 69, 98, 119, 132, 135, 136, 153, 154, 155, 190 Governing Board, 190, 210 Gp120, 190, 207 Grade, 8, 14, 22, 24, 41, 54, 102, 103, 106, 118, 190, 220 Graft, 17, 190, 192, 194 Graft Rejection, 190, 194 Grafting, 17, 190, 194 Gram-negative, 176, 190 Granulocytes, 190, 218, 226 Granuloma, 190, 199 Granuloma Inguinale, 190, 199 Groin, 4, 190, 195 Gynaecological, 57, 190 Gynecology, 47, 55, 57, 59, 76, 136, 190 H Hair Color, 107, 190 Hair follicles, 190, 226 Haploid, 190, 209 Haplotypes, 22, 190 Haptens, 20, 168, 190 Headache, 191, 195 Health Behavior, 7, 191 Health Education, 154, 191 Health Services, 154, 191 Health Status, 191 Hematologic malignancies, 5, 8, 191 Hematopoietic Stem Cell Transplantation, 5, 191 Hemoglobin, 186, 191, 198 Hemorrhoids, 169, 191 Hepatitis, 13, 29, 100, 124, 125, 132, 135, 155, 191, 202 Hepatocytes, 191 Hereditary, 191, 216 Heredity, 189, 191 Herpes virus, 109, 114, 115, 191, 225 Herpes Zoster, 191 Heterogeneity, 104, 168, 192 Heterotrophic, 188, 192 Histidine, 192, 195 Histology, 23, 192, 206
234 Human Papilloma Virus
Homogeneous, 107, 192 Homologous, 26, 192, 202, 222, 223 Hormonal, 179, 192 Hormone, 45, 179, 188, 192, 195, 216, 218, 222 Horny layer, 185, 192 Horseradish Peroxidase, 185, 192 Hospital Records, 7, 192 Host, 6, 10, 12, 111, 116, 117, 118, 124, 125, 171, 174, 192, 193, 194, 216, 217, 225, 226 Humoral, 55, 108, 116, 124, 190, 192 Humour, 192 Hybrid, 11, 154, 192, 204 Hybridization, 42, 50, 69, 100, 111, 133, 192, 204 Hydrogen, 172, 173, 174, 181, 186, 192, 202, 203, 204, 206, 212 Hydrogen Bonding, 192, 204 Hydrolysis, 105, 172, 176, 181, 192, 208, 210, 212 Hygienic, 119, 193 Hyperplasia, 17, 193 Hypersensitivity, 27, 39, 193, 216 Hyperthermia, 181, 193 Hypertrophy, 193 Hypoxia, 11, 193 I Id, 82, 90, 156, 162, 164, 193 Imidazole, 172, 193 Immortal, 55, 87, 121, 193 Immune function, 22, 193 Immune Sera, 193 Immune system, 12, 21, 29, 154, 155, 170, 193, 194, 199, 225, 226 Immune Tolerance, 10, 193 Immunity, 9, 11, 14, 17, 61, 70, 75, 124, 125, 167, 185, 193, 194, 199, 223 Immunization, 11, 116, 193, 194 Immunoassay, 185, 193 Immunodeficiency, 4, 21, 38, 63, 119, 124, 125, 131, 132, 136, 148, 154, 155, 167, 193 Immunodeficiency syndrome, 131, 136, 148, 154, 193 Immunodominant Epitopes, 15, 193 Immunogenic, 10, 56, 124, 194 Immunoglobulin, 61, 170, 194, 202 Immunohistochemistry, 14, 17, 41, 194 Immunologic, 6, 8, 16, 109, 176, 193, 194, 207, 214 Immunology, 8, 15, 21, 39, 51, 56, 73, 75, 167, 168, 188, 192, 194 Immunosuppressant, 188, 194
Immunosuppressive, 6, 12, 47, 189, 194 Immunosuppressive therapy, 47, 194 Immunotherapy, 5, 8, 9, 10, 15, 27, 57, 117, 127, 128, 194 Impairment, 183, 187, 194 Implant radiation, 194, 196, 214, 226 Implantation, 178, 194 In situ, 4, 17, 23, 33, 38, 41, 42, 44, 49, 54, 57, 62, 67, 69, 70, 75, 80, 81, 194 In Situ Hybridization, 17, 38, 41, 42, 44, 62, 67, 75, 81, 194 In vivo, 6, 13, 17, 18, 19, 25, 27, 57, 80, 85, 98, 102, 104, 194 Incision, 4, 194, 196 Incubated, 102, 194 Incubation, 112, 126, 194 Indicative, 10, 132, 194, 206, 225 Induction, 11, 17, 27, 30, 40, 58, 97, 105, 124, 169, 181, 194 Infarction, 179, 194, 201 Infection Control, 132, 195 Infertility, 66, 154, 195 Influenza, 125, 195 Infusion, 6, 117, 195 Inguinal, 4, 195, 199 Initiation, 5, 14, 122, 195 Inlay, 195, 215 Inorganic, 118, 176, 195, 202, 221 Insight, 18, 26, 195 Insulin, 121, 195 Insulin-dependent diabetes mellitus, 195 Interferon, 58, 59, 60, 68, 72, 74, 88, 100, 195 Interferon Alfa-2b, 74, 195 Interferon-alpha, 72, 195 Interleukin-2, 123, 195 Intermittent, 196, 199 Internal radiation, 196, 214, 226 Interphase, 175, 196 Interstitial, 173, 196, 226 Intestine, 121, 173, 177, 196, 197 Intracellular, 190, 194, 196, 211, 218 Intradermal Tests, 70, 196 Intraductal carcinoma, 182, 196 Intraepithelial, 4, 6, 14, 32, 36, 37, 39, 41, 47, 49, 51, 54, 59, 63, 68, 75, 77, 80, 81, 85, 87, 96, 98, 99, 123, 175, 196 Intravenous, 117, 195, 196 Intrinsic, 168, 172, 196 Invasive, 14, 16, 22, 23, 39, 46, 58, 99, 100, 105, 110, 113, 123, 139, 175, 193, 196, 200 Invasive cervical cancer, 110, 113, 123, 196
Index 235
Ion Channels, 171, 196 Ionizing, 168, 184, 196, 214 Ions, 172, 173, 182, 183, 192, 196, 212 Irradiation, 16, 20, 100, 196, 227 Irritants, 183, 196 K Kb, 108, 146, 196 Keratin, 24, 197 Keratinocytes, 17, 18, 46, 57, 58, 75, 87, 105, 197 Keratitis, 109, 197 Keratolytic, 197, 209 Keratosis, 36, 197 Kidney Pelvis, 197, 224 Kidney stone, 197, 224 Kinetic, 196, 197 L Labile, 177, 197 Lacrimal, 52, 197 Laminin, 172, 186, 197 Large Intestine, 177, 181, 196, 197, 214, 218 Laryngeal, 42, 51, 60, 67, 96, 116, 123, 197 Larynx, 120, 134, 170, 197, 223 Laser Surgery, 153, 197 Latency, 116, 197 Latent, 105, 113, 197 Lens, 99, 197, 226 Lentigo, 17, 197 Leprosy, 27, 197 Lesion, 6, 19, 22, 32, 96, 101, 126, 175, 190, 198 Lethal, 12, 198 Leucine, 123, 198 Leukemia, 8, 44, 191, 198, 212 Leukocytes, 173, 176, 190, 195, 198 Leukoplakia, 132, 134, 198 Library Services, 162, 198 Lice, 155, 198 Life cycle, 12, 18, 132, 188, 198 Ligament, 198, 212 Ligase, 113, 198 Ligase Chain Reaction, 113, 198 Ligation, 198 Limbic, 27, 198 Lipid, 89, 195, 198 Lipoprotein, 190, 198, 226 Liver, 101, 115, 171, 172, 180, 184, 189, 191, 197, 198 Localization, 8, 18, 34, 56, 57, 59, 75, 81, 194, 198 Localized, 175, 187, 194, 197, 198, 208, 209 Locomotion, 198, 209
Longitudinal study, 7, 14, 199 Long-Term Care, 9, 15, 199 Loop, 26, 118, 199 Lymph, 43, 64, 175, 184, 192, 199, 215, 217, 221 Lymph node, 43, 64, 175, 199, 215, 217 Lymphatic, 184, 195, 199, 201, 217, 219, 220, 222 Lymphatic system, 199, 217, 219, 220, 222 Lymphocyte, 6, 12, 14, 21, 167, 170, 199, 200 Lymphocyte Count, 167, 199 Lymphocyte Subsets, 12, 199 Lymphoepithelioma, 48, 199 Lymphogranuloma Venereum, 132, 190, 199 Lymphoid, 6, 12, 170, 199 Lymphokines, 8, 199 Lymphoma, 8, 12, 191, 199 Lysine, 109, 199 M Macula, 188, 199 Macula Lutea, 199 Macular Degeneration, 28, 199 Magnetic Resonance Imaging, 34, 200 Major Histocompatibility Complex, 14, 17, 190, 200 Malignancy, 28, 68, 113, 116, 121, 127, 200, 206 Malignant mesothelioma, 25, 200, 201 Malignant tumor, 174, 200 Malnutrition, 119, 200 Mammary, 19, 30, 52, 56, 64, 72, 81, 200 Manifest, 131, 200 Matrix metalloproteinase, 24, 200 Mediate, 24, 111, 200 Mediator, 195, 200 Medical Records, 192, 200, 216 Medicament, 110, 117, 200 MEDLINE, 147, 200 Megakaryocytes, 173, 200 Meiosis, 200, 203, 222 Melanocytes, 17, 200, 201, 203 Melanoma, 16, 53, 101, 201 Melanosomes, 200, 201 Mental Health, iv, 5, 146, 149, 201, 213 Mentors, 18, 201 Mercury, 187, 201 Mesenchymal, 185, 201 Mesothelial, 25, 201 Mesothelioma, 200, 201 Metabolite, 172, 182, 201
236 Human Papilloma Virus
Metaplasia, 35, 201 Metastasis, 24, 57, 200, 201 Metastatic, 8, 11, 100, 101, 201, 217 Metastatic cancer, 101, 201 Methionine, 182, 201 MI, 85, 121, 165, 201 Microbe, 201, 223 Microbiological, 115, 201 Microbiology, 9, 44, 55, 80, 133, 167, 171, 201 Microorganism, 97, 177, 201, 206, 226 Microscopy, 12, 26, 33, 172, 192, 202 Microtubules, 202, 206 Mineralocorticoids, 167, 179, 202 Mitochondrial Swelling, 202, 203 Mitosis, 170, 175, 202 Mitotic, 29, 175, 186, 202, 222 Mitotic Spindle Apparatus, 175, 202 Mode of Transmission, 96, 202 Modeling, 182, 202 Modification, 189, 202, 213 Monitor, 6, 62, 202, 204 Monoclonal, 26, 196, 202, 214, 226 Morphological, 17, 61, 183, 188, 200, 202 Morphology, 18, 64, 118, 202 Mucocutaneous, 114, 202 Mucopurulent, 73, 202 Mucosa, 39, 118, 123, 128, 202, 221 Mucus, 183, 202 Multivalent, 125, 202 Muscular Dystrophies, 183, 203 Mutagen, 203 Myalgia, 195, 203 Myocardium, 201, 203 N Nasal Mucosa, 195, 203 Nasopharynx, 134, 199, 203 NCI, 1, 23, 145, 176, 203 Necrosis, 100, 170, 189, 194, 201, 203 Need, 3, 4, 6, 20, 62, 98, 103, 117, 118, 123, 127, 131, 133, 135, 148, 154, 157, 190, 200, 203 Neoplasia, 4, 6, 12, 21, 22, 32, 35, 36, 37, 39, 41, 46, 47, 49, 51, 54, 59, 63, 67, 68, 75, 77, 80, 81, 85, 87, 96, 98, 99, 115, 123, 136, 175, 203 Neoplasm, 36, 203, 206, 217, 224 Neoplastic, 24, 51, 64, 99, 100, 103, 131, 199, 203 Neural, 192, 203 Neurophysiology, 181, 203 Neutralization, 26, 203
Neutrons, 168, 196, 203, 213, 214 Nevus, 197, 203 Nitrogen, 101, 169, 186, 187, 203 Nonmelanoma skin cancer, 65, 203 Nonoxynol, 114, 115, 203 Nuclear, 11, 49, 64, 77, 110, 127, 183, 186, 188, 203, 204, 211, 212, 216 Nucleates, 175, 204 Nuclei, 168, 183, 189, 200, 202, 203, 204, 205, 212, 217 Nucleic acid, 39, 59, 97, 102, 103, 104, 111, 112, 116, 133, 174, 189, 192, 194, 203, 204, 213 Nucleic Acid Hybridization, 39, 59, 192, 204 Nucleic Acid Probes, 111, 204 Nucleoprotein, 59, 80, 204 Nucleosomes, 85, 204 Nucleus, 13, 27, 107, 118, 127, 170, 176, 180, 186, 188, 200, 203, 204, 211, 212, 221 Nutritional Status, 6, 204 O Obstetrics, 37, 42, 47, 55, 57, 59, 60, 61, 76, 88, 132, 136, 204 Octamer, 74, 204 Odds Ratio, 204, 215 Odour, 171, 204 Ointments, 204, 206 Oligonucleotide Probes, 81, 111, 198, 204 Oncogene, 14, 19, 20, 33, 51, 58, 72, 84, 86, 105, 115, 205 Oncogenic, 5, 6, 9, 12, 14, 15, 20, 22, 28, 29, 50, 61, 77, 110, 111, 113, 132, 205, 212, 213 Oncology, 33, 35, 38, 45, 47, 50, 51, 54, 67, 70, 72, 80, 85, 86, 113, 126, 133, 205, 215 Oocytes, 75, 205 Open Reading Frames, 119, 205 Ophthalmic, 42, 205, 216 Ophthalmology, 21, 52, 187, 205 Opportunistic Infections, 17, 22, 167, 205 Opsin, 205, 215 Optic Disk, 181, 199, 205 Optic Nerve, 205, 215, 216 Oral Health, 205 Oral Hygiene, 134, 205 Organ Culture, 205, 223 Organelles, 180, 200, 201, 205 Oropharynx, 35, 120, 205 Osteosarcoma, 205, 212 Outpatient, 153, 205 Ovum, 189, 198, 205, 227
Index 237
Oxidation, 170, 172, 180, 205 P P53 gene, 11, 73, 89, 206, 212 Paclitaxel, 88, 206 Palate, 203, 206 Palliative, 206, 222 Pancreas, 172, 195, 206, 224 Pancreatic, 59, 121, 206 Pancreatic Ducts, 59, 206 Pancreatic Juice, 206 Pap test, 98, 136, 206 Papillomavirus, 21, 26, 54, 83, 84, 85, 86, 87, 89, 96, 97, 102, 103, 106, 107, 108, 110, 111, 114, 116, 118, 122, 123, 148, 154, 192, 206 Paraffin, 42, 127, 206 Parasite, 109, 206, 217, 224 Parasitic, 183, 198, 206, 208 Particle, 26, 206, 219, 223 Parturition, 204, 206 Patch, 107, 127, 128, 186, 198, 206 Pathogen, 20, 124, 132, 194, 206 Pathogenesis, 13, 18, 28, 52, 113, 206 Pathologic, 49, 170, 172, 174, 179, 193, 206, 207, 213 Pathologic Processes, 170, 207 Pathologies, 122, 207 Patient Education, 152, 160, 162, 165, 207 Pelvic, 4, 64, 154, 155, 207, 212 Pelvic inflammatory disease, 154, 155, 207 Penis, 74, 105, 178, 183, 207 Pentoxifylline, 86, 207 Peptide, 8, 10, 13, 17, 19, 21, 27, 29, 124, 184, 197, 207, 210, 212 Peptide T, 17, 207 Perception, 93, 178, 207 Perfusion, 193, 207 Perianal, 44, 84, 178, 207 Perinatal, 4, 132, 207 Perineal, 60, 88, 207 Perineum, 207 Peripheral blood, 6, 191, 195, 207 Peripheral Nerves, 198, 207 Petroleum, 206, 207 Phallic, 187, 207 Pharmacokinetic, 207 Pharmacologic, 169, 208, 223 Pharynx, 134, 195, 203, 205, 208 Phenotype, 46, 65, 105, 111, 208 Phonation, 170, 208 Phosphodiesterase, 207, 208 Phospholipases, 208, 218
Phospholipids, 187, 198, 208 Phosphorus, 36, 80, 174, 208 Phosphorylation, 29, 127, 208 Photocoagulation, 176, 208 Photodynamic therapy, 208 Photofrin, 57, 208 Physical Examination, 176, 208 Physiologic, 172, 181, 208, 211, 214 Physiology, 184, 190, 203, 208 Pigment, 200, 201, 203, 205, 208 Pituitary Gland, 179, 208 Plana, 120, 208 Plant Viruses, 13, 208 Plants, 12, 121, 174, 189, 202, 208, 210, 223 Plaque, 101, 209 Plasma, 170, 175, 184, 187, 188, 191, 202, 209, 212, 217, 225 Plasma cells, 170, 209 Platelet Activation, 209, 218 Platelet Aggregation, 169, 207, 209 Platinum, 117, 176, 199, 209 Pleated, 197, 209 Pleural, 201, 209 Podophyllin, 85, 155, 209 Podophyllotoxin, 86, 186, 209, 222 Polyethylene, 114, 209 Polymerase, 39, 41, 43, 47, 48, 50, 67, 75, 76, 81, 83, 104, 113, 114, 209 Polymerase Chain Reaction, 39, 41, 43, 47, 48, 50, 67, 75, 76, 81, 83, 104, 113, 114, 209 Polymorphism, 63, 66, 210 Polypeptide, 56, 109, 123, 168, 174, 177, 178, 185, 187, 192, 210, 212, 227 Polyposis, 68, 177, 210 Polysaccharide, 170, 175, 210, 212 Polyunsaturated fat, 89, 210 Posterior, 169, 176, 206, 210 Postnatal, 210, 220 Postsynaptic, 210, 218 Post-translational, 25, 210 Potentiating, 11, 120, 210 Potentiation, 210, 218 Practice Guidelines, 149, 210 Precancerous, 101, 210 Precursor, 16, 22, 76, 110, 113, 120, 127, 171, 183, 185, 187, 210, 212 Pregnancy Outcome, 154, 210 Premalignant, 24, 105, 113, 134, 210 Prenatal, 183, 210 Prevalence, 22, 29, 65, 66, 73, 80, 87, 89, 122, 204, 210
238 Human Papilloma Virus
Prickle, 197, 210 Probe, 20, 32, 111, 112, 198, 204, 210 Progeny, 12, 211 Prognostic factor, 85, 211 Progression, 3, 5, 6, 14, 21, 22, 23, 24, 53, 60, 105, 116, 118, 169, 211, 224 Progressive, 6, 27, 105, 115, 175, 180, 182, 190, 203, 209, 211, 224 Progressive disease, 6, 211 Proliferating Cell Nuclear Antigen, 58, 211 Proline, 9, 177, 211 Promoter, 9, 24, 65, 105, 107, 111, 115, 117, 125, 211 Prone, 69, 211 Prophase, 203, 205, 211, 222 Prophylaxis, 154, 211, 217, 225 Proportional, 7, 185, 211 Prospective study, 67, 199, 211 Prostaglandin, 101, 211 Prostaglandins A, 211, 212 Prostate, 8, 87, 110, 172, 212, 224 Protease, 22, 24, 109, 212 Protease Inhibitors, 22, 24, 212 Protein C, 107, 168, 171, 177, 197, 198, 204, 212, 226 Protein Conformation, 168, 197, 212 Protein Kinases, 13, 100, 212 Protein p53, 105, 212 Protein S, 25, 133, 172, 178, 189, 212, 216 Proteoglycans, 172, 186, 212 Proteolytic, 177, 187, 212 Prothrombin, 212, 222 Protocol, 14, 62, 114, 212 Protons, 168, 192, 196, 212, 213 Proto-Oncogene Proteins, 206, 212, 213 Proto-Oncogene Proteins c-mos, 206, 213 Protozoa, 183, 201, 213 Proximal, 124, 182, 213 Pruritic, 213, 217 Pruritus, 4, 213 Psoriasis, 101, 213 Psychiatry, 187, 213 Psychogenic, 170, 213 Public Health, 21, 32, 41, 119, 149, 213 Public Policy, 147, 213 Publishing, 30, 131, 213 Puerperium, 204, 213 Pulmonary, 173, 179, 213, 221 Pulse, 202, 213 Purgative, 209, 213 Purines, 213, 218
Q Quality of Life, 7, 213 R Radiation, 9, 19, 50, 80, 123, 184, 186, 188, 193, 196, 213, 214, 226 Radiation therapy, 186, 196, 214, 226 Radio Waves, 181, 214 Radioactive, 62, 192, 194, 196, 204, 205, 214, 224, 226 Radioimmunotherapy, 8, 214 Radioisotope, 100, 204, 214 Radiolabeled, 8, 196, 214, 226 Radiotherapy, 4, 38, 50, 173, 196, 214, 227 Randomized, 32, 183, 214 Rape, 132, 214 Reagent, 17, 110, 214 Receptor, 13, 26, 27, 29, 46, 49, 51, 58, 80, 85, 167, 170, 178, 190, 207, 214, 218 Recombinant, 6, 9, 10, 18, 25, 27, 34, 100, 107, 125, 195, 214, 225 Recombinant Proteins, 6, 214 Rectal, 153, 214 Rectum, 45, 84, 170, 177, 181, 188, 197, 212, 214 Recur, 155, 214 Recurrence, 7, 14, 43, 64, 126, 153, 214 Refer, 1, 177, 187, 188, 191, 198, 199, 203, 214 Refraction, 214, 219 Regimen, 6, 183, 215 Regional lymph node, 4, 215 Relative risk, 23, 167, 215 Remission, 214, 215 Renal pelvis, 74, 197, 215, 223 Reproduction Techniques, 210, 215 Resection, 7, 100, 101, 215 Residual disease, 8, 215 Respiration, 174, 202, 215 Respiratory syncytial virus, 125, 215 Response rate, 15, 215 Restoration, 114, 215, 226 Resuscitation, 183, 215 Retina, 27, 176, 181, 197, 199, 205, 215, 216, 226 Retinal, 27, 178, 181, 205, 215, 216 Retinal Neovascularization, 28, 215 Retinal Vein, 216 Retinoblastoma, 13, 45, 59, 65, 71, 105, 111, 216 Retinoblastoma Protein, 45, 59, 216 Retinoid, 46, 216 Retinol, 215, 216
Index 239
Retinopathy, 28, 181, 216 Retrospective, 76, 216 Retrospective study, 76, 216 Retrovirus, 60, 216 Rheology, 207, 216 Rheumatism, 216 Rheumatoid, 117, 216 Rheumatoid arthritis, 117, 216 Ribosome, 216, 223 Rigidity, 208, 216 Risk factor, 4, 29, 68, 110, 134, 185, 211, 215, 216 Rods, 205, 215, 216 Rotavirus, 26, 216 Rotavirus Vaccines, 26, 216 Rubella, 13, 132, 216, 217 Rubella Virus, 13, 217 S Safe Sex, 132, 217 Salivary, 180, 217, 221 Salivary glands, 180, 217 Sarcoma, 12, 132, 205, 217 Satellite, 29, 217 Scabies, 155, 217 Schistosome, 29, 217 Scleroproteins, 197, 217 Screening, 8, 15, 16, 17, 23, 25, 33, 40, 76, 98, 99, 115, 126, 127, 134, 154, 176, 217 Sebaceous, 196, 217, 226 Secondary tumor, 201, 217 Secretion, 179, 185, 192, 195, 202, 217 Semen, 43, 183, 212, 217 Semisynthetic, 117, 186, 217, 222 Senescence, 71, 217 Senile, 197, 209, 217 Sequence Homology, 100, 207, 217 Sequencing, 110, 210, 217 Serine, 9, 100, 184, 213, 218 Serology, 22, 218 Serous, 184, 218 Serum, 7, 97, 169, 177, 193, 202, 218 Sex Education, 152, 218 Sexual Abstinence, 153, 218 Sexual Partners, 47, 218 Shock, 29, 121, 218, 224 Side effect, 103, 115, 154, 167, 218, 223 Signal Transduction, 27, 218 Sindbis Virus, 168, 218 Skeleton, 167, 211, 218 Skin graft, 17, 218 Skin Neoplasms, 185, 209, 218 Skull, 218, 222
Small intestine, 182, 192, 196, 218 Smallpox, 218, 225 Smooth muscle, 65, 88, 169, 218 Social Environment, 213, 219 Sodium, 101, 119, 202, 219 Sodium Dodecyl Sulfate, 119, 219 Soft tissue, 173, 218, 219 Solid tumor, 8, 169, 219 Soma, 219 Somatic, 29, 192, 200, 202, 219, 222 Somatic mutations, 29, 219 Sound wave, 181, 219 Soybean Oil, 210, 219 Specialist, 157, 219 Specificity, 7, 15, 168, 184, 193, 219 Spectrum, 36, 83, 99, 104, 114, 119, 175, 214, 219, 225 Speculum, 97, 98, 219 Sperm, 64, 115, 153, 169, 176, 219 Spermatozoa, 217, 219, 220 Spermicide, 115, 136, 153, 220 Sphincter, 197, 220 Spinal cord, 171, 175, 207, 220 Spindle-cell, 33, 220 Spinous, 127, 185, 197, 220 Spirochete, 220, 222 Spleen, 10, 12, 180, 199, 220 Spontaneous Abortion, 210, 220 Sporadic, 216, 220 Squamous cell carcinoma, 4, 9, 28, 36, 45, 51, 52, 54, 62, 66, 69, 80, 112, 134, 185, 220 Squamous cells, 203, 220 Squamous Epithelium, 64, 220 Squamous intraepithelial lesion, 41, 110, 220 Stabilizer, 108, 220 Staging, 4, 220 Standardize, 17, 220 Stem cell transplantation, 8, 191, 220 Stem Cells, 6, 191, 220 Stent, 88, 221 Sterility, 64, 195, 221 Steroids, 120, 179, 189, 221 Stillbirth, 210, 221 Stimulus, 186, 196, 197, 221 Stomach, 121, 181, 186, 188, 192, 208, 218, 220, 221 Strand, 40, 87, 112, 119, 209, 221 Stress, 11, 188, 216, 221 Stromal, 24, 49, 173, 221 Stromal Cells, 173, 221
240 Human Papilloma Virus
Subacute, 195, 199, 221 Subclinical, 39, 40, 58, 71, 74, 105, 195, 221 Subcutaneous, 124, 183, 221 Submaxillary, 185, 221 Submucous, 134, 221 Subspecies, 219, 221, 225 Substrate, 185, 221 Sulfates, 219, 221 Suppression, 12, 19, 68, 71, 179, 221 Suppressive, 20, 221 Surfactant, 108, 203, 219, 221, 226 Survival Rate, 4, 9, 221 Symphysis, 212, 221 Symptomatic, 136, 222 Synaptic, 218, 222 Synchrotron, 26, 222 Syphilis, 119, 132, 135, 154, 155, 222 Systemic, 60, 88, 101, 173, 174, 195, 196, 214, 222, 223, 225, 226 T Telomerase, 28, 222 Temporal, 7, 18, 199, 222 Tenesmus, 183, 222 Teniposide, 117, 222 Teratogenesis, 209, 222 Terminator, 177, 222 Therapeutics, 8, 19, 75, 115, 222 Thermal, 171, 182, 203, 209, 222 Thigh, 190, 222 Threonine, 9, 100, 207, 213, 218, 222 Thrombin, 109, 187, 209, 212, 222 Thrombomodulin, 212, 222 Thrombosis, 212, 222 Thymidine, 173, 222 Thymus, 193, 199, 222 Thyroid, 9, 51, 222 Tin, 209, 223 Tissue Culture, 96, 223 Tooth Preparation, 167, 223 Topical, 86, 114, 126, 128, 206, 223 Toxic, iv, 100, 101, 103, 115, 116, 118, 180, 184, 189, 193, 209, 223 Toxicity, 16, 21, 84, 115, 182, 201, 223 Toxicokinetics, 223 Toxicology, 35, 148, 223 Toxins, 170, 184, 194, 214, 223 Trachea, 173, 197, 208, 222, 223 Transcriptase, 28, 216, 222, 223 Transduction, 27, 49, 218, 223 Transfection, 18, 46, 104, 172, 223 Transfer Factor, 193, 223 Transitional cell carcinoma, 33, 48, 65, 223
Translation, 12, 223 Translational, 8, 25, 223 Translocate, 27, 223 Transmitter, 171, 196, 200, 223 Transplantation, 8, 183, 193, 200, 224 Trauma, 191, 203, 224 Trichomoniasis, 155, 224 Tuberculosis, 17, 179, 224 Tumor marker, 8, 172, 224 Tumor model, 10, 19, 224 Tumor suppressor gene, 19, 66, 105, 111, 206, 216, 224 Tumor-derived, 13, 224 Tumorigenic, 12, 13, 104, 224 Tumour, 54, 71, 117, 224 U Ubiquitin, 45, 224 Unconscious, 193, 224 Ureter, 74, 75, 197, 215, 223, 224 Urethra, 207, 212, 224 Urethritis, 69, 224 Uric, 100, 213, 224 Urinary, 47, 155, 189, 224 Urinary tract, 155, 224 Urinary tract infection, 155, 224 Urine, 173, 185, 197, 215, 224 Urogenital, 189, 190, 224 Uterus, 175, 179, 184, 225 V Vaccination, 10, 19, 21, 27, 124, 125, 225 Vaccinia, 9, 10, 97, 225 Vaccinia Virus, 10, 97, 225 Vagina, 59, 106, 174, 175, 177, 225, 226 Vaginal, 3, 49, 98, 111, 137, 154, 204, 225, 226 Vaginitis, 174, 225 Vaginosis, 155, 225 Varicella, 225 Variola, 225 Vascular, 7, 27, 60, 88, 176, 184, 194, 195, 225 Vascular endothelial growth factor, 7, 225 Vector, 16, 18, 107, 108, 117, 124, 223, 225, 227 Vein, 196, 204, 216, 217, 225 Venereal, 96, 120, 132, 155, 156, 222, 225 Venous, 191, 212, 225 Venules, 173, 184, 225 Verruca, 46, 120, 225 Vertebral, 208, 225 Veterinary Medicine, 147, 225 Vidarabine, 85, 225
Index 241
Viral Load, 4, 22, 23, 85, 225 Viral vector, 100, 124, 225 Virion, 12, 26, 102, 108, 127, 226 Virulence, 171, 223, 226 Viscera, 219, 226 Vitreous Body, 215, 226 Vitreous Hemorrhage, 181, 226 Vitro, 5, 6, 13, 14, 16, 17, 18, 21, 25, 27, 28, 30, 53, 57, 81, 85, 89, 102, 105, 183, 194, 209, 218, 223, 226 Vivo, 6, 17, 27, 226 Vulgaris, 120, 226 Vulva, 4, 53, 54, 71, 226 W Wart, 34, 64, 116, 121, 155, 197, 226 Wetting Agents, 203, 226
White blood cell, 170, 194, 198, 199, 202, 209, 226 Windpipe, 173, 208, 222, 226 Wound Healing, 200, 226 X Xenograft, 169, 224, 226 X-ray, 26, 31, 100, 188, 196, 203, 204, 214, 220, 226 X-ray therapy, 196, 226 Y Yeasts, 174, 188, 208, 227 Yellow Fever, 13, 227 Yellow Fever Virus, 13, 227 Z Zoster, 225, 227 Zygote, 178, 227 Zymogen, 212, 227
242 Human Papilloma Virus
Index 243
244 Human Papilloma Virus
