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

MIFEPRISTONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES ...

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MIFEPRISTONE 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 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Mifepristone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00729-0 1. Mifepristone-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on mifepristone. 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 MIFEPRISTONE .......................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Mifepristone .................................................................................. 3 E-Journals: PubMed Central ....................................................................................................... 31 The National Library of Medicine: PubMed ................................................................................ 31 CHAPTER 2. NUTRITION AND MIFEPRISTONE ................................................................................ 77 Overview...................................................................................................................................... 77 Finding Nutrition Studies on Mifepristone................................................................................. 77 Federal Resources on Nutrition ................................................................................................... 79 Additional Web Resources ........................................................................................................... 79 CHAPTER 3. ALTERNATIVE MEDICINE AND MIFEPRISTONE .......................................................... 81 Overview...................................................................................................................................... 81 National Center for Complementary and Alternative Medicine.................................................. 81 Additional Web Resources ........................................................................................................... 88 General References ....................................................................................................................... 89 CHAPTER 4. PATENTS ON MIFEPRISTONE ....................................................................................... 91 Overview...................................................................................................................................... 91 Patents on Mifepristone ............................................................................................................... 91 Patent Applications on Mifepristone ........................................................................................... 94 Keeping Current .......................................................................................................................... 95 CHAPTER 5. PERIODICALS AND NEWS ON MIFEPRISTONE ............................................................. 97 Overview...................................................................................................................................... 97 News Services and Press Releases................................................................................................ 97 Academic Periodicals covering Mifepristone ............................................................................... 99 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................. 101 Overview.................................................................................................................................... 101 U.S. Pharmacopeia..................................................................................................................... 101 Commercial Databases ............................................................................................................... 102 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 105 Overview.................................................................................................................................... 105 NIH Guidelines.......................................................................................................................... 105 NIH Databases........................................................................................................................... 107 Other Commercial Databases..................................................................................................... 109 APPENDIX B. PATIENT RESOURCES ............................................................................................... 111 Overview.................................................................................................................................... 111 Patient Guideline Sources.......................................................................................................... 111 Finding Associations.................................................................................................................. 113 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 115 Overview.................................................................................................................................... 115 Preparation................................................................................................................................. 115 Finding a Local Medical Library................................................................................................ 115 Medical Libraries in the U.S. and Canada ................................................................................. 115 ONLINE GLOSSARIES................................................................................................................ 121 Online Dictionary Directories ................................................................................................... 121 MIFEPRISTONE DICTIONARY ................................................................................................ 123 INDEX .............................................................................................................................................. 175

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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 mifepristone 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 mifepristone, 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 mifepristone, 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 mifepristone. 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 mifepristone, 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 mifepristone. 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 MIFEPRISTONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on mifepristone.

Federally Funded Research on Mifepristone The U.S. Government supports a variety of research studies relating to mifepristone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable 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 mifepristone. 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 mifepristone. The following is typical of the type of information found when searching the CRISP database for mifepristone: •

Project Title: ATF3 IN BETA CELL SIGNALING, EXPRESSION & DESTRUCTION Principal Investigator & Institution: Hai, Tsonwin; Associate Professor; Molecular & Cellular Biochemistry; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Goal and Significance: Diabetes is a major health problem in the U.S. Many years of research indicate that beta cell destruction plays an

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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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important role in the pathogenesis and complication of diabetes. The goal of this proposal is to elucidate the roles of Activating Transcription Factor 3 (ATF3), a stressinducible gene, in stress-induced signal transduction, beta cell dysfunction and destruction. The proposed research will test the following hypotheses. (1) Aim 1: To test the hypothesis that ATF3 is induced in beta cells by stress signals, at least in part, through the MAPK and NFkB pathways. Dominant negative molecules that block the activation of these pathways will be used to determine whether they could inhibit the induction of ATF3 in beta cells by stress signals (IL-1beta, hyperglycemia, and hyperlipidemia). In addition, constitutively active mutants that activate these pathways will be used to determine whether they could induce the expression of ATF3 in the absence of exogenously applied signals. (2) Aim 2: To test the hypothesis that expression of ATF3 leads to beta cell dysfunction, destruction and the development of diabetes. The mifepristone-inducible system will be used to generate transgenic mice expressing ATF3 in the islets in an inducible manner. These mice will be characterized for morphological, immunohistochemical and physiological parameters, and for islet cell death and cell proliferation. (3) Aim 3: To test the hypothesis that ATF3 plays an essential role in cytokine-induced beta cell dysfunction and destruction. Islet cells will be isolated from wild type (ATF3+/+), heterozygous (ATF3+/-) and homozygous (ATF3-/-) ATF3 knockout mice. Cells will be subjected to pro-inflammatory cytokines, nitric oxide donor S-nitroso glutathione (GSNO), or medium (control). Cell death will be analyzed at various time points to determine whether ATF3 is "necessary" for stress signals to induce efficient beta cell death. In addition, islet functions will be analyzed to determine whether ATF3 is necessary for cytokines to induce beta cell dysfunction. For in vivo experiments, wild type and knockout mice will be injected with streptozotocin (STZ) to induce diabetes. Blood glucose levels and diabetes incidence will be analyzed to determine whether ATF3 knockout mice are less sensitive to STZ than wild type mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BEHAVIORAL/NEUROENDOCRINE REGULATION OF WOUND HEALING Principal Investigator & Institution: Sheridan, John F.; Professor; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002 Summary: (adapted from investigator's abstract): The hypothesis of this proposal is that physiologic changes associated with stress, down-regulate pro-inflammatory cytokine, chemokine and growth factor gene expression resulting in alterations in cellular trafficking and activation, thus impairing wound healing. The long term goal of these studies is to understand the mechanisms underlying stress-related changes between the neuroendocrine and inflammatory responses that are responsible for altered wound healing. The aims of the proposal are 1) to determine the influence of stress on the pattern and kinetics of chemokine, pro-inflammatory cytokine and growth factor gene expression during the early stages of wound healing, 2) to determine the stress-induced, neuro-endocrine mechanisms that regulate pro-inflammatory cytokine, chemokine and growth factor gene expression during wound healing and 3) to determine the mechanism of the anti-glucocorticoid actions of androstenediol (a metabolite of DHEA) and delineate its ability to regulate pro-inflammatory cytokines (IL-1 alpha and beta and TNF alpha), chemokines (KC, IP10, MCP-1 and MIP 1 alpha) and growth factor (KGF, VEGF and TGF beta )gene expression as a therapeutic strategy to improve wound healing in stressed individuals. The proposal makes use of histological, molecular biology and pharmacological approaches to address the specific aims. The in vivo study

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of wound healing is accompanied by in vitro studies of the direct effect of glucocorticoids and AED (a metabolite of dihydroxyepiandrosterone) on cellular expression of transcription factors and cytokines. Restraint stress repeated over several days is to be used as a stress paradigm, skin wounding will be used to determine the rate of healing and the profile of cytokines and chemokines during the healing period. Subsequent studies will use an in vitro approach in which neutrophils and macrophages isolated from female mice will be incubated with corticosterone to determine the effect of LPS induced stimulation of cytokine and chemokine release and on changes in NFkappa beta. In addition, the influence of AED on wound healing, cytokine and chemokine production and transcription factor NF-kappa beta will also be addressed in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BREAST TUMOR INHIBITION BY ANTIPROGESTINS Principal Investigator & Institution: Wiehle, Ronald D.; Zonagen, Inc. 2408 Timberloch Pl, B-4 the Woodlands, Tx 77380 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2003 Summary: (provided by applicant): The use of antiestrogens in women for the treatment of breast cancer, although far from ideal, is one of the few therapies currently available. The following revised proposal outlines experiments to be performed under a SBIR that would clarify the properties of certain new antiprogestins as adjuvant therapies analogous to current therapies utilizing tamoxifen and SERMs. In May 1999, a Licensing Agreement between Zonagen and the NICHD was finalized to develop new antiprogestins. We expect that the new generation of compounds will be used for a number of indications where the etiology is dominated by progesterone. The promise of the first antiprogestin, RU 486, has gone unfulfilled because of its extensive antiglucocorticoid effects and the political backlash to its use as an abortifacient. Indications for antiprogestin use could include oral contraception, labor induction, cervical ripening, hormone replacement therapy (HRT), and treatment of uterine fibroids, endometriosis, and especially breast cancer. It is the overall aim of this proposed SBIR to determine effects on the growth of previously established rodent breast cancers with the ultimate intention of introducing a new adjuvant treatment for human breast cancer. The rat model has been shown to respond to antiprogestins such as RU 486 with a decrease in the growth of lesions following treatment. There is a need to determine whether our lead compound. CDB-4124, has the same anticancer properties as RU 486 as a proof-of-principle. Moreover, we need to determine the doseresponse of that lead compound. Phase II would determine whether a secondary class of compounds have similar activity, whether the best compound(s) reduce the ultimate size and appearance of lesions if used prior to frank appearance, and their synergism with antiestrogens. Additionally, the possibility that antiprogestins can inhibit breast tumor growth and development would greatly enhance the potential of such compounds for chemoprevention and other long-term therapies (fibroids, endometriosis, HRT) and such a drug should find wide and unqualified acceptance among women. PROPOSED COMMERCIAL APPLICATION: Antiprogestational compounds from the Licensing Agreement could fill Zonagen's developmental pipeline with drugs for those diseases and, potentially, several other indications. New antiprogestins discovered by NICHD and realized as drugs through this proposed SBIR, satisfy the need to bring the results of government-sponsored science into the public domain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Mifepristone

Project Title: CELLULAR SYNAPTOGENESIS

AND

MOLECULAR

MECHANISMS

OF

Principal Investigator & Institution: Keshishian, Haig S.; Professor; Molecular and Cellular Physio; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 31-JUL-2005 Summary: (provided by applicant): This project will examine the cellular and molecular mechanisms that govern the establishment and plasticity of synapses in a model genetic system, the Drosophila neuromuscular junction. These problems will be studied using manipulations at the cellular and molecular level, applied with single cell precision during embryonic and larval development. We have previously characterized several of the cellular events involved in the establishment and growth of the synapse. We are now poised to apply novel tools, developed in the lab, to test hypotheses about the role of electrical activity during neuromuscular development and functional plasticity. The methods include the use "Electrical Knock Out" or EKO ion channels, that suppress electrical activity in specific motoneurons and/or muscle fibers. There are four specific goals in this proposal. First, we plan to expand our repertoire of tools for controlling electrical activity in vivo to include channel constructs enhance electrical activity, providing a complementary set of tools to the EKO constructs. Second, using these methods, several hypotheses about the roles of electrical activity in regulating neuromuscular connectivity and synaptic refinement during embryogenesis and larval development will be tested. Third, the role of neuromuscular activity in regulating the functional plasticity of the synapse will be examined. The latter analysis will focus on the putative orthograde and retrograde signals which are proposed to regulate a form of synaptic homeostasis at the neuromuscular junction. Finally, by focally control electrical activity in specific cells, we propose to carry out a genetic screen to identify the molecules whose functions are involved in regulating synaptic development and plasticity. The many molecular-genetic tools available in Drosophila, combined with vital imaging and electrophysiological analyses, makes this system particularly wellsuited to uncover the molecular mechanisms that govern synaptic development and dynamic functional plasticity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINE REGULATION IN MODELS OF ENDOMETRIOSIS Principal Investigator & Institution: Taylor, Robert N.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002 Summary: Endometriosis is a common human gynecologic disorder associated with dysmenorrhea, pelvic pain and reduced fertility. Prevalence estimates range from 250%, although most scholars of endometriosis believe that it occurs in approximately 10% of reproductive aged American women. The annual United States health costs attributable to endometriosis exceed $1 billion. Recent studies suggest that endometriosis implants activate local peritoneal inflammatory responses that mediate the clinical symptoms. We hypothesize that the recruitment and subsequent accumulation of activated macrophages in the peritoneal cavity was an early and requisite step in the establishment of endometriosis implants and identified elevated concentrations of inflammatory and angiogenic cytokines (RANTES, IL-6, IL-8, VEGF) in peritoneal fluid of women with endometriosis. We propose to investigate the regulation of synthesis and secretion of one representative chemokine, RANTES, a potent chemoattractant for monocytes and T cells. We demonstrated that RANTES is localized

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in the stromal compartment of normal endometrium and endometriosis implants and that both mRNA and protein are expressed in endometrial stromal but not epithelial cells in vitro. In Specific Aim #1 we will use highly purified (>95%) primary stromal cell cultures to compare RANTES production in eutopic and ectopic cells from normal subjects, women with endometriosis and women with unexplained infertility. Our preliminary data indicate that RANTES protein secretion differs in the former two conditions. In Specific Aim #2, we will study the ability the natural ovarian steroid hormones (estradiol, progesterone), antagonists (tamoxifen, RU486, danazol) and other cytokines (TNF-alpha), IL-1alpha and beta, interferon-gamma) to modulate RANTES expression in vitro at the mRNA and protein levels. An expression vector containing 477 base pairs of the human RANTES gene promoter cloned upstream of a luciferase reporter will be used to map the transcriptional regulatory motifs in transiently transfected endometrial and endometriosis stromal cells. Specific Aim #3 will be executed in collaboration with Dr. Osteen using his in vivo model of human endometrium transplanted into the nude mouse peritoneal cavity. Hormones and cytokines that up- and down-regulate immunoreactive RANTES in vitro will be administered to mice bearing human endometrial implants to determine if these compounds regulate human RANTES in intact tissues in vivo. Cognate anti-hormones or cytokine neutralizing antibodies will be administered to confirm that the RANTES modulating effects are specific. It is likely that RANTES and other chemokines play early, requisite play early, requisite roles in the inflammatory process that accompanies this syndrome. These molecules should provide ideal targets for the future development of novel therapeutic antagonists for the medical treatment of endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLAGEN-BINDING PROTEINS IN SOFTENING OF UTERINE CERVIX Principal Investigator & Institution: Kokenyesi, Robert; Assistant Professor; ObstetricsGynecology; St. Louis University St. Louis, Mo 63103 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): The uterine cervix functions as a rigid, connective tissue-rich sphincter at the distal end of the uterus. In the course of normal pregnancy, the cervix gradually becomes softer as the collagenous stroma is remodeled. Correct timing of cervical softening is important because too early cervical softening (incompetent cervix) can either directly lead to premature delivery, or indirectly hasten premature delivery by constituting a weakened sphincter in premature labor. Ultrastructural findings in all species show that cervical softening is concomitant with the dissociation and disorganization of the normally tightly woven and well- aligned collagen fibers and bundles. However, the molecular basis for cervical softening is poorly understood. Collagen-binding proteins such as the proteoglycans decorin, fibromodulin, and lumican, and glycoproteins thrombospondin-2 and type V collagen have been shown to affect collagen fibrillogenesis in vitro or collagen fibril morphology and tissue mechanical properties in vivo. The applicant's hypothesis is that the reorganization of the fibrous collagen network is the cause of cervical softening, and that this reorganization is achieved by the altered synthesis or distribution of cervical collagen-binding matrix proteins. The applicant proposes to pursue the following specific aims in a mouse model of cervical softening: 1. Determine the relationship between expression pattern of collagen-binding matrix proteins, the cervical mechanical properties, and the collagen fiber morphology in uterine cervix of normal mice, and transgenic mice deficient in decorin, fibromodulin, lumican and thrombospondin. 2. The

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potential functional defect in cervical softening will be tested by the induction of preterm delivery with the antiprogesterone agent Mifepristone (RU-486). The significance of these studies is that a better understanding of the molecular basis of cervical softening will allow the development of techniques for early detection of susceptibility for premature cervical softening, and the design of effective preventative measures, or treatment regimens for better patient management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMBINED ANTI-ANGIOGENIC TARGETING OF CHOLINE KINASE

THERAPY

AND

SIRNA

Principal Investigator & Institution: Bhujwalla, Zaver M.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 10-AUG-2003; Project End 31-JUL-2008 Summary: Although the progression of cancer arrives at a common end point of organ failure, cachexia and death, common pathways are rare in cancer. Over the past decade one common pathway consistently revealed by MR spectroscopic studies is the elevation of phosphocholine and total choline in cancer cells and solid tumors. Data obtained by us demonstrate that phosphocholine in cancer cells is related to malignant transformation, endothelial cancer cell interaction, invasion and metatasis. Therefore the elevation of phosphocholine presents a unique target to exploit for therapy. In this proposal we intend to develop molecular biology strategies to target choline kinase in oxygenated as well as hypoxic cells using small interfering RNA (siRNA) to inhibit the transcription of choline kinase. We have chosen choline kinase as a target since it is the enzyme which converts choline to phosphocholine. Choline kinase inhibition will be induced in normoxic cells using a mifepristone inducible system or in hypoxic cells using the hypoxia response element to drive the formation of the siRNA. In vivo, the hypoxia inducible system will also be combined with anti-angiogenic treatment which will create hypoxia over a larger region of the tumor. The effects of choline kinase inhibition with or without anti-angiogenic therapy on invasion, metabolism and vascularization will be determined with combined MRI and MRSI. Optical imaging will be used to detect hypoxia, and histology to detect metastasis. Microarray analyses will be performed characterize molecular alterations. These studies will be performed with three human breast cancer cell lines and their transgenic counterparts, studied as cells and as solid tumors in vivo. Cells in hypoxic environments in solid tumors are the most resistant to radiation and chemotherapy, and are most likely to lead to recurrence of the disease. Our cancer invasion studies have shown that the presence of endothelial cells in the proximity of cancer cells under hypoxic conditions confers an advantage in invasion of the cancer cells. Approaches to enhance the action of anti-angiogenic therapy, by exploiting the hypoxia induced by anti-angiogenic therapy to further target a key pathway in cancer cells would minimize the risk of increased invasion and act synergistically with anti-angiogenic therapy in killing cancer cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF MENSTRUAL BLEEDING DISTURBANCES IN WOMEN Principal Investigator & Institution: Fraser, Ian S.; Sydney Centre for Reproductive Hlth Res Health Research Ashfield, Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2007

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Summary: (provided by applicant): This application is designed to evaluate two promising approaches to the treatment of prolonged and frequent episodes of breakthrough bleeding which sometimes accompany the use of the implantable, progestogen-only implant Implanon. These erratic episodes of bleeding can be a major reason for discontinuation of use. There is increasing evidence that continuous exposure to progestogens results in a tendency for the endometrium to release active enzymes called matrix metalloproteinases [MMPs] which can promote premature breakdown of the tissue. Inhibition of the action of these enzymes may stabilize the endometrium and improve the bleeding pattern. A commonly used tetracycline compound, Doxycycline, has strong anti-MMP action and preliminary evidence in a mouse model of menstruation suggests that it may indeed stabilize the endometrium. There is preliminary evidence that a short course of an antiprogesterone (Mifepristone) may also stabilize the endometrium, and it is postulated that a combination of an antiprogesterone with estrogen may be even more effective. Preliminary evidence in mice indicates that estrogen exposure of the endometrium in the absence of progesterone strongly inhibits the formation of new blood vessels and simultaneous anti-progesterone exposure will mimic this situation. Antiprogesterones probably also have a direct effect in inhibiting angiogenesis, and the combination maybe a clinically valuable treatment. A triple combination of antiprogesterone, estrogen and anti MMP agent may have additive effects because of the likelihood of differing actions. This study aims to explore these possibilities in large scale clinical studies, scientific study of vascular and molecular changes in endometrium and with the exploration of molecular mechanisms in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENGINEERED HEMATOPOIETIC CELL SELF-RENEWAL AND DEATH Principal Investigator & Institution: Lasky, Larry C.; Pathology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Cord blood is a recent advance in marrow replacement therapy, allowing much less frequent and severe graft-vs-host disease from a reliable, easily procured source. Unfortunately, delayed production of white cells and platelets, especially in larger patients, is a life-threatening and expensive problem. Ways of expanding stem and progenitor cells have been reported, and even used in human trials. To date, no improvement in speed of recovery has been reported. This may be due to inadequate numbers of early stem cells, or to lack of more committed progenitors. The proposed study will alter the earliest hematopoietic cells by inserting genes to be controlled by exogenous small molecules. Genes that promote stem cell self-renewal and, separately, inhibit programmed cell death (apoptosis), will be used. With this new control system, the cells will respond without altering the extant cellular machinery. The control molecules will either not be naturally occurring or will be found in very low amounts in animals. Once the genes are inserted, the cells will be signaled to multiply without differentiation (self-renew) and without apoptosis, causing birth of many more early blood-forming cells. Then a portion of the cells will be expanded with growth factors that will cause differentiation, by turning off the self-renewal gene and continuing to block apoptosis. For in vivo use, apoptosis will be allowed to start again under normal cell control before the cells are infused, to prevent possible uncontrolled growth. The early cells will provide long-term engraftment and the differentiated cells will provide rapid recovery. Control of the two inserted genes will be possible after

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Mifepristone

infusion, should it be needed. The effect of the control molecules on blood cell formation kinetics once the cells are in place in the animals will also be studied. At each stage of the project, expanded cells will be evaluated for surface markers and gene expression using flow cytometry, in situ hybridization, and PCR, as well as in vitro colony forming and long term culture initiating cell systems, and in vivo in appropriately selected mice. This project will introduce a control system that will be silent in the absence of control molecules, and will allow exploration of the use of large numbers of blood-forming cells both in the lab and, possibly, clinically. In addition to marrow replacement, the cells may be usable for the production of other cells and tissues, especially given recent discoveries regarding stem cell plasticity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHANOL EFFECTS ON RECOVERY FROM THERMAL INJURY Principal Investigator & Institution: Kovacs, Elizabeth J.; Professor; Cell Bio & Neurobio & Anatomy; Loyola University Chicago Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 30-APR-2004 Summary: (Adapted from the Investigator's Abstract) The overall goal of the proposed studies is to determine mechanisms by which acute ethanol exposure prior to thermal injury diminishes the magnitude of cell mediated immunity to a greater extent than observed following thermal injury alone. Nearly 100,000 people each year are admitted to hospitals due to burn injury and about half of those patients are reported to have been drinking alcohol. Alcohol exposure is not only a risk factor for the events that lead up to the fire-related accidents, it also leads to increased morbidity and mortality among burned patients. Burn patients who had moderate to high blood alcohol levels on admission stay in the hospital twice as long, required 60% more surgical procedures and more rigorous antibiotic therapy, and are twice as likely to suffer serious infectious complications than burn patients not exposed to alcohol having identical burn injuries. These complications arise in alcohol exposed individuals because of ethanol mediated effects on cell mediated immune functions. The investigators hypothesize that the level of circulating ethanol at the time of thermal injury dictates the degree of immune dysfunction. The proposed studies are designed to explore mechanisms by which alcohol alters mitogen-induced splenocyte proliferation and contact hypersensitivity responses in thermally injured mice given different levels of ethanol at various intervals prior to injury. Since macrophages from these mice suppress the function of lymphocytes, studies will examine the production of macrophage-derived immunomodulatory mediators, including interleukin-6 (IL-6) and transforming growth factor -beta (TGFB). If it is demonstrated that acute ethanol exposure prior to thermal injury alters splenocyte proliferation by increasing the production of IL-6 and/or TGFB, then further studies will 1) define the cells responsible for the aberrant production of these mediators and 2) use neutralizing antibodies directed against those cytokines in vivo and in vitro to determine if normal immune cell function can be restored. Since glucocorticoids are elevated after stress (such as alcohol exposure and burn injury) and can alter cytokine production leading to immunosuppression, further investigation will be directed at examining whether alcohol exposure prior to thermal injury alters the kinetics or magnitude of circulating corticosterone. In the event that the PI observe elevated plasma glucocorticoid levels which correlate with depressed immune function, then they will attempt to block the actions of glucocorticoids in vivo using the glucocorticoid receptor antagonist, RU486. At the present time, it is unclear how acute ethanol exposure affects cell mediated immunity and overall rates of mortality and morbidity among burned individuals. Studies such as those described herein will yield

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11

valuable information regarding the mechanisms by which acute ethanol exposure adversely affects immune cell function in the burned individual. In addition, these studies may also provide information necessary for improving treatments and therapies for the burned, immunosuppressed patient. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATING DRUG TOXICITY IN HUMANIZED YEAST Principal Investigator & Institution: Miller, Charles A.; Environmental Health Sciences; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2004; Project Start 01-SEP-2004; Project End 31-AUG-2007 Summary: (provided by applicant): Hsp90 proteins are the central members of a multiprotein complex called the Hsp90 chaperosome. Several of these Hsp90-client protein complexes are targets for cancer therapies or represent potential targets for future research. The steroid hormone receptors are the best-characterized client proteins of the Hsp90 chaperosome. Drugs designed to target a particular Hsp90 complex or its client protein (oncogenes/kinases/receptors) often produce toxic effects due to non-specific actions on other client protein-Hsp90 complexes. Consequently, a system to assess this "collateral damage" based on drug interactions with Hsp90 and/or its client proteins would be valuable in initial screens designed to eliminate toxic compounds. As a hypothetical example, if a compound (such as a geldanamycin derivative) designed to affect ErbB2-Hsp90 complexes also affected glucocorticoid receptor-Hsp90 complexes with similar potency, the compound would be flagged for potential toxicity and possibly eliminated from further testing. We are developing a "humanized" yeast-based system to assess drugs that may act on the Hsp90 chaperosome and its client proteins. The yeast chaperone components functioning in this pathway are being replaced by their human counterparts to create a relevant model for toxicity studies. Our previous studies with human aryl hydrocarbon receptor, Hsp90 isoproteins, and co-chaperones in yeast provide "proof of concept" for this model toxicity system. The proposed new yeast strains will provide novel, inexpensive, high-throughput toxicity screens that are relevant for the prediction of human toxicity. The Specific Aims of this proposal are 1) to construct yeast strains with human homodimeric steroid hormone receptors that coexpress critical human Hsp90 proteins and co-chaperones and 2) to validate signaling responses in these strains using known Hsp90 inhibitors and steroid hormone agonists and antagonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION

GLUCOCORTICOIDS,

STRESS

AND

BLOOD

PRESSURE

Principal Investigator & Institution: Scheuer, Deborah A.; Assistant Professor; Pharmaceutical Sciences; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): Increasing evidence implicates elevated glucocorticoid activity in the pathogenesis of cardiovascular disease, while altered neural control of the circulation has long been identified with cardiovascular disease. Few studies have investigated glucocorticoid-mediated modulation of neural control of the circulation. The long-term goal of this research program is to identify pathways and mechanisms by which glucocorticoids modulate neural control of the circulation. The central hypothesis for the proposed experiments is that prolonged in vivo activation of glucocorticoid receptors in the dorsal hindbrain contributes significantly to effects of

12

Mifepristone

glucocorticoids on arterial pressure regulation. To test this hypothesis experiments will be performed in conscious rats with normal or chronically elevated systemic glucocorticoid concentrations, and with the dorsal hindbrain chronically treated with the glucocorticoid corticosterone (cort), or the glucocorticoid type II receptor (GR) antagonist, Mifepristone (Mif). The Specific Aims are: Aim 1: To test the hypothesis that glucocorticoids act within the dorsal hindbrain to reduce the buffering capacity of arterial baroreflex control of renal sympathetic nerve activity and heart rate. Aim 2: To test the hypothesis that glucocorticoids act within the dorsal hindbrain to enhance arterial pressure, heart rate and endocrine responses to single and repeated episodes of restraint stress. Aim 3: To test the hypothesis subpopulations of the neuronal cells that are activated (detected by c-fos) during increases in blood pressure or restraint stress also express glucocorticoid receptors. Dual label immunohistochemistry will be used to anatomically map subpopulations of dorsal hindbrain neuronal cells that are positive for both c-fos and glucocorticoid receptors following increases in blood pressure or restraint stress. This project is innovative because we have developed a method for prolonged application of glucocorticoid receptor ligands to the dorsal hindbrain that circumvents previous difficulties with delivering these steroids to the central nervous system. The results from these experiments will provide the basis for further studies to identify the specific neurons involved in glucocorticoid-mediated modulation of neural control of blood pressure, providing new opportunities for treatment and prevention of cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GUTLESS VECTOR MEDIATED HYPERLIPIDEMIA AND ATHEROSCLEROSIS

GENE

THERAPY

OF

Principal Investigator & Institution: Chan, Lawrence; Professor of Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: The overall objective of this project is to develop gutless adenovirus vectors for use in experimental animals, to determine the best protocol for prolonged expression following delivery in vivo, and to use these vectors to express low density lipoprotein receptor (LDLR) and very low density lipoprotein receptor (VLDLR) in animal models of familial hypercholesterolemia (FH). The specific aims are (i) We will examine the effect of long-term expression of VLDLR and LDLR in transgenic mice with an LDLR -/background using an inducible binary transactivation system. This system was developed by investigators in Project 3. Different levels of expression of the transgene can be accomplished by graded subphysiological doses of an exogenous compound RU486. (ii) We will develop gutless adenovirus vectors expressing reporter genes (e.g. alpha1- antitrypsin), VLDLR and LDLR which will be tested in mice and rhesus monkeys. (iii) We will develop a protocol for the repeated administration of gutless vectors to mice and rhesus monkeys. Transient immunosuppression protocols and vectors of different serotypes will be tested. (iv) We will test and compare the gutless vectors expressing mouse LDLR and VLDLR in LDLR -/- mice for their efficacy in reversing the hypercholesterolemia and their general health effects, and the extent of aortic atherosclerosis. (v) We will examine the effect of hepatic transfer of the rhesus LDLR and VLDLR genes in heterozygous and possibly homozygous LDLR-deficient rhesus monkeys. This project interacts closely with Project 2 for the gutless vector development, and Project 3 for the regulated expression system. It will be supported by the scientific Cores A (Primate Core), B (Vector Production Core) and C (Pathology Core).

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13

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

Project Title: HIV IN WOMEN: DEPRESSION AND IMMUNITY Principal Investigator & Institution: Evans, Dwight L.; Professor and Chair; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Psychiatric morbidity has been associated with HIV disease since the beginning of the AIDS epidemic. Most of the clinical literature to date has focused on psychiatric issues in men who are HIV seropositive. There has been little data regarding the prevalence of psychiatric disorders in HIV infected women, despite the fact that HIV remains among the leading causes of death for US women between the ages of 25 and 44. HIV also is the leading cause of death among African American women in this age group. We found that the proportion of women with current major depression was four times higher in HIV positive women compared to HIV seronegative women. This high rate of major depression coupled with the recent and largest epidemiology study to date indicating that depression is associated with increased mortality in HIV-infected women, underscores the need for studies to ascertain the relationship of major depression, immunity, and HIV disease progression in HIV infected women. The potential immune mechanisms by which depression may influence HIV disease progression and mortality remain to be understood. In our studies of HIV infected men, we have found depression associated alterations of immune cytotoxic cells suggesting that killer lymphocytes might mediate the effects of depression on HIV disease progression. Although previous studies have focused almost exclusively on HIV infected men, we have recently found that women with depression exhibit significant reductions in natural killer cell activity as well as increases in activated CD8 lymphocytes and viral load. The proposed study of HIV seropositive women, largely of minority representation, is designed to provide important information on 1) the underlying immune mechanisms by which depression my influence HIV-1 replication and thereby HIV disease progression; and 2) three potential mechanisms of action whereby depression my influence immunity and HIV disease progression. The present study may also help determine whether conventional antidepressants (SSRIs) as well as novel antidepressant pharmacotherapies (substance P antagonists and glucocorticoid antagonists) might benefit HIV-infected individuals and extend survival with HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONAL REGULATION OF INFLAMMATORY RESPONSES & CELL GROWTH IN ENDOMETRIOSIS Principal Investigator & Institution: Sidell, Neil; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002 Summary: SUBPROJECT ABSTRACT NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREGNANCY

HORMONAL

REGULATION

OF

THE

CERVIX

DURING

Principal Investigator & Institution: Sherwood, Orrin D.; Molecular & Integrative Phys; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820

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Mifepristone

Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The three objectives of this proposal will examine the regulation of both growth and softening of the cervix during pregnancy. In the rat, cervical growth is accompanied by an accumulation of epithelial and stromal cells. The first objective is to determine the influence of relaxin, estrogen and progesterone on the rates of apoptosis and proliferation of cervical cells. At three-day intervals throughout the second half of pregnancy, relaxin's action will be neutralized with a monoclonal antibody for rat relaxin, estrogen's action will be blocked with the estrogen antagonist ICI 182,780, and progesterone's action will be blocked with the progesterone antagonist RU 486. The rates of apoptosis will be determined immunohistochemically by employing the terminal deoxynucleotidyl transferase-mediated UTP end-labeling (TUNEL) method. Electron microscopy will be used to evaluate treatment effects on percent of cell types undergoing apoptosis, stromal collagen, and epithelium functional complexes. Light microscopy immunohistochemistry will be used also to evaluate treatment effects on epithelium functional complexes. Rates of cell proliferation will be determined immunohistochemically by measuring the rate of incorporation of 5-bromo-2deoxyuridine (BrdU) into proliferating cells and also by measuring the expression of proliferating cell nuclear antigen (PCNA). RU 486 induces delivery and promotes cervical softening at term in women and other species. The second objective will test the hypothesis that relaxin is more effective than RU 486 in promoting cervical softening near term. To accomplish this, the effects of RU 486 and relaxin on cervical extensibility will be determined at term in relaxin-deficient rats in which endogenous relaxin is immunoneutralized throughout the second half of pregnancy. Morphometric analysis will also be done to compare the effects of RU 486 and relaxin on the histological characteristics of the cervix. This proposal will also examine a novel procedure for both inducing delivery and softening the cervix. Induction of labor more than doubled to 19% between 1989 and 1998. The success of labor induction is influenced by the state of the cervix. The active component of the two approved agents for cervical softening (Prepidil and Cervidil) is PGE2, and this prostaglandin causes uterine hyperstimulation in a significant percentage of patients. Relaxin has potential advantages over PGE2 because relaxin not only promotes rapid and marked growth and softening of the cervix, but also reduces uterine contractility. The third objective will test the hypothesis that the administration of RU 486 for induction of delivery in combination with relaxin for induction of cervical softening is more effective in promoting rapid and safe delivery in pregnant rats than is the administration of RU 486 alone. Treatment with RU 486 alone and in combination with exogenous relaxin will be done at term with relaxin-deficient rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPRESSION

HPA

AXIS/DOPAMINE

INTERACTIONS

IN

PSYCHOTIC

Principal Investigator & Institution: Schatzberg, Alan F.; Professor and Chair; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-MAY-2004 Summary: The proposed research continues previously funded studies on the pathophysiology of psychotic major depression (PMD), a severe and often debilitating form of depression. Results thus far indicate that PMD patients have increased and phase advanced corticotropin (ACTH) circadian rhythms, increased overnight cortisol levels, and prefrontal cognitive deficits that may originate in glucocorticoid (GC) effects on ascending mesocortical dopamine (DA) pathways. Parallel studies in animals

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indicate that chronic administration of GC's decreases DA utilization in rat prefrontal cortex, and impairs prefrontal DA mediated cognitive performance in squirrel monkeys. Moreover, GC receptor blockade by mifepristone produces rapid relief of PMD cognitive impairments as measured by psychiatric tests. Based on these results, the proposed studies test the following four hypotheses: (l) Hypothalamic-pituitary-adrenal (HPA) axis dysregulation in PMD is associated with specific cognitive impairments in executive functions, attention, and semantic analysis, and with correlated volumetric losses and functional activation abnormalities in prefrontal cortex and the hippocampal formation, as measured by structural and functional magnetic resonance imaging (fMRI); (2) Mifepristone treatment relieves PMD cognitive deficits and delusional symptoms as measured by psychometric and psychiatric tests, normalizes the PMD phase advance in plasma ACTH circadian rhythms, and is accompanied by functional reorganizations in prefrontal cortical networks as measured by fMRI; (3) In monkeys, chronic stress induces prefrontal cognitive impairments analogous to those seen previously with chronic UC treatment, and these stress effects are blocked by mifepristone; and (4) In rats, mifepristone blocks the effects of chronic stress and chronic GC treatment on prefrontal DA metabolism. The approaches used to address these aims move across the boundaries of clinical psychopharmacology, basic behavioral neuroscience, experimental neurochemistry, and functional neuroimaging, with the ultimate goal of understanding why some depressed patients become psychotic or otherwise cognitively impaired, and uncovering new and faster methods of treatment for PMD and related psychotic disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION

HYPOGLYCEMIA

AND

AUTONOMIC

NERVOUS

SYSTEM

Principal Investigator & Institution: Freeman, Roy; Associate Professor of Neurology; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study have documented unequivocally that improved glycemic control decreases the incidence and progression of microvascular complicatons of diabetes. The implementation of regimens to rigorously control blood sugar in diabetic patients has led to an increased incidence of severe iatrogenic hypoglycemic events that have limited glycemic management of diabetes mellitus. Recent antecedent iatrogenic hypoglycemia impairs the neuroende:rine and autonomic response to subsequent hypoglycemia - a disorder known as hypoglycemia associated autonomic failure - thus increasing the predisposition to severe hypoglycemia. It is not known whether antecedent hypoglycemia has more general effects on autonomic nervous system function. Impaired autonomic function is associated with increased mortality and morbidity in individuals with diabetes mellitus. If hypoglycemia induces generalized autonomic dysfunction it may further increase the mortality and morbidity associated with diabetes mellitus. The goal of this research is to understand the mechanisms of hypoglycemia associated autonomic failure. The proposed studies test the hypothesis that antecedent hypoglycemia not only impairs the counterregulatory response to subsequent hypoglycemia but also impairs cardiovascular autonomic function in nonhypoglycemic individuals. These studies will examine those markers of cardiovascular autonomic function that, when impaired, are associated with increased morbidity and mortality in patients with diabetes. Furthermore, we hypothesize that antecedent hypoglycemia causes a rise in serum cortisol and that cortisol activation of

16

Mifepristone

glucocorticoid receptors mediates the development of hypoglycemia associated autonomic failure. The specific aims for the proposal are to assess autonomic control of cardiovascular function following antecedent euglycemia and hypoglycemia. In addition, we will determine whether administration of a glucocorticoid receptor antagonist, mifepristone, prior to antecedent hypoglycemia improves the autonomic and neuroendocrine response to subsequent hypoglycemia in healthy men and women. Thus, the broad long term objectives of the proposal are to fully understand the mechanisms and consequences of hypoglycemia associated autonomic failure with the ultimate goal of finding an efficacious treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIFE-SPAN EXTENSION /METHIONINE SULFOXIDE REDUCTASE Principal Investigator & Institution: Hoshi, Toshinori; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: Oxidative damages to cellular constituents are postulated to accelerate aging and shorten the life-span of an organism. Aging in many species is accompanied by declines in physical activity and reproductive vigor. A variety of strategies to minimize oxidative damages to increase the life- span have been proposed. The amino acid methionine is easily oxidized and the repair of oxidized methionine is catalyzed by the enzyme peptide methionine sulfoxide reductase (MSRA). Here we will examine lifespan extension roles of the anti-oxidant MSRA in the model organism Drosophila. Previous results suggested that constitutive over-expression of MSRA throughout the entire Drosophila life markedly extended the life-span. The study proposed here will test whether it is possible to extend the life-span and delay senescence-induced declines in the physical activity level and reproductive capacity if MSRA is over- expressed after the animal reaches adulthood. Temporally-controlled over-expression of MSRA is achieved using the RU486-dependent "GeneSwitch" protocol. The effects of induced MSRA over-expression on the survival distribution, oxidative stress resistance, physical activity and reproductive behavior are examined. The results expected will provide insights into the mechanism underlying the life-extension effect of MSRA and implicate MSRA a possible therapeutic agent to slow aging and senescence-induced changes in physiology and behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MIFEPRISTONE MISOPROSTOL

FOLLOWED

ON

THE

SAME

DAY

BY

Principal Investigator & Institution: Creinin, Mitchell D.; Associate Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLEEDING

MIFEPRISTONE

FOR

PREVENTION

OF

BREAKTHROUGH

Principal Investigator & Institution: Jain, John K.; Assistant Professor; Obstetrics & Gynecology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033

Studies

17

Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Progestin-only contraceptives such as depomedroxyprogesterone acetate (DMPA) represent one of the most effective classes of contraceptives but are limited by high discontinuation rates due to breakthrough bleeding especially during the first year of use. Mifepristone is a competitive progesterone receptor antagonist. When Mifepristone was given to normally cycling primates, a near-amenorrheic state was achieved. Mifepristone has been shown to decrease breakthrough bleeding in women using levonorgestrel implants. Although estrogen receptor expression increases after Mifepristone administration, a paradoxical anti-proliferative effect is seen in the endometrium. That has lead some investigators to conclude that mifeprisone can suppress estrogen receptor transcriptional activity through non-competitive means such as sequestration of estrogen receptor transcriptional cofactors. The result being lack of endometrial proliferation and development of an atrophic endometrial state. With less endometrial tissue to shed, bleeding diminishes and amenorrhea ensues. We propose to conduct a 14-month prospective, randomized, double-blind, placebo-controlled study of 50 mg of Mifepristone administered every 2 weeks for 12 cycles to 50 new starters of DMPA in order to determine the incidence of bleeding and ovulation. Bleeding data will be gathered with the use of daily dairies and ovulation monitored by thrice-weekly urine collections. Seven endometrial biopsies obtained pre- and post - treatment will be analyzed using immunohistochemical and quantitative RT-PCR methods to evaluate levels of estrogen and progesterone receptor isoforms. Biopsies will also be evaluated histologically. In order to determine the function of estrogen receptors following DMPA and Mifepristone we will establish primary endometrial cell culture and test estrogen function by measuring markers of proliferation such as SRC, MIB-1 and MMT and correlating results to in vivo biopsy samples. We are currently conducting a pilot study similar to the one proposed to gather preliminary data and to test the feasability of a larger trial. If Mifepristone is shown to safely decrease the incidence of breakthrough bleeding, more women may continue DMPA and not place themselves at risk of an unintended pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS TO STUDY GONADAL TUMOR DEVELOPMENT Principal Investigator & Institution: Matzuk, Martin; Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2006 Summary: Cancer is a major cause of morbidity and mortality in our society. Like other malignancies, ovarian and testicular cancers arise through multiple genetic alterations. Using a knockout mouse model, we discovered that the inhibins, alpha:beta heterodimeric members of the transforming growth factor beta superfamily, are tumor suppressors with specificity for the gonads and adrenal cortex. In mice lacking alpha inhibin, neither inhibin A (alpha:betaA) nor inhibin B (alpha:betaB) is produced, and granulosa/Sertoli cell tumors of the ovaries and testis develop as early as 4 weeks of age with 100% penetrance. The ovarian tumors are often mixed tumors consisting of both granulosa cell and Sertoli cell components. Castration of male and female inhibin a knockout mice leads to a high incidence of sex steroidogenic adrenal cortical tumors (66 of 67 mice). Mice with gonadal or adrenal tumors are rapidly affected by a cancer wasting syndrome which mimics the cachexia syndromes associated with human cancer cases. Using a genetic approach to generate double mutant mice lacking both alpha inhibin and activin receptor type IIA (ActRIIA), we showed that tumor-produced activin

18

Mifepristone

directly signals through ActRIIA in the liver and stomach to cause this wasting syndrome. Using similar genetic approaches, we have shown the following: (1) Overexpression of the activin antagonist follistatin alleviates some of the cachexia-like symptoms caused by the circulating activins and slows the tumor development; (2) Absence of gonadotropins FSH and LH, prevents tumor development; (3) Lack of only FSH slows tumor development in both sexes, but mortality rates are sexually dimorphic (0% survival of females, 70% survival of males) demonstrating that FSH functions differentially in ovarian and testicular tumorigenesis; and (4) Absence of the cyclindependent kinase (Cdk) inhibitor p27(Kip1) speeds the process of gonadal tumorigenesis. The studies in this competitive renewal proposal will continue to define the inhibin signaling process and the mechanism of inhibin action in gonadal and adrenal function in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURODEGENERATION AND ABETA PLAQUES IN KOKANEE SALMON Principal Investigator & Institution: Hobbs, Steven L.; Ecology and Evolutionary Biology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-AUG-2002 Summary: (provided by applicant): I intend to investigate aging related physiological and pathological changes in kokanee salmon (Oncorhynchus nerka kennerlyi), which are also characteristic of human Alzheimer's disease. These include cerebral beta amyloid (Abeta) plaque formation, chronically elevated cortisol and accelerated neurodegeneration. The hypothesis that chronically elevated cortisol and starvation (normal kokanee spawning conditions) can induce neurodegeneration and Abeta plaque formation will be tested by injecting absorbable pellets of cortisol and forcing starvation in hatchery reared kokanee salmon. The physiological effects of natural cortisol elevation during upstream migration and spawning will also be examined by blocking cortisol receptors with RU-486 administered in absorbable pellets. The amyloid cascade hypothesis will be investigated in kokanee salmon by administering an inhibitor of Abeta production during migration and spawning. Lastly pathological similarities in neurodegeneration and Abeta plaque formation between spawning kokanee salmon, older humans and humans with AD will be investigated by immunohistochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROENDOCRINE CONTROL OF ANTERIOR PITUITARY HORMONES Principal Investigator & Institution: Kineman, Rhonda D.; Assistant Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 02-JUL-1981; Project End 31-JAN-2007 Summary: (provided by applicant): Growth hormone (GH) promotes protein synthesis and lipolysis. In turn, metabolic disturbances are associated with alteration in GH production which contribute to the pathophysiology of clinically relevant disorders such as malnutrition, anorexia nervosa, obesity and diabetes. Despite the strong association between metabolism and GH, little is known regarding the basic mechanisms by which perturbations in metabolic pathways bring about changes in GH synthesis and release. Therefore, this application will determine the mechanisms by which alterations in nutrient availability; 1) regulate hypothalamic expression of neuropeptides essential for normal pituitary GH production (GH-releasing hormone [GHRH] and somatostatin

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19

[SRIF]), and 2) modify pituitary sensitivity to the GH-stimulatory peptides, GHRH and ghrelin. It has been proposed that changes in circulating leptin (an adipocyte factor) and ghrelin (a GH-releasing peptide produced in the stomach) mediates hypothalamic expression of GHRH and SRIF through activation of neuropeptide Y (NPY) neurons. To test this hypothesis, the effects of fasting on neuropeptide mRNA levels, in mice harboring defects in leptin synthesis (ob/ob), tissue source of leptin (AZIP-F1), NPY synthesis (NPY-/-), SRIF synthesis (smst-/-) and SRIF signaling (ss1l/2-/-) will be examined by ribonuclease protection assay and in situ hybridization. Also the effects of fasting in normal mice following exogenous hormone replacement (to increase NPY, leptin or ghrelin), pharmacological treatment (to block endogenous NPY production) or passive immunoneutralization (to block the actions of ghrelin) will be tested. Fasting not only alters expression of GH-regulatory neuropeptides but also enhances pituitary sensitivity to GHRH and ghrelin by increasing GHRH-R and GHS-R mRNA levels. In vitro, FFAs alone or in conjunction with glucocorticoids increase GHS-R synthesis. Therefore it is hypothesized that fasting induced elevations in FFA and glucocorticoids are required to enhance pituitary receptor synthesis and sensitivity, and thus compensate for fasting-induced alteration in central signals. To test this hypothesis, studies will examine the ability of fasting to alter pituitary receptor expression (by quantitative RT-PCR) and dynamic GH release (by RIA of serial blood samples) following blockade of FFA formation (by the anti-lipolytic Acipimox) or glucocorticoid actions (by the glucocorticoid receptor antagonist, RU-486). Also primary rat and nonhuman primate (baboon) pituitary call cultures will be used to determine if FFA and glucocorticoids mediate their effects on receptor synthesis via transcriptional or posttranscriptional processes and if the effects of FFA can be mimicked by activation of the putative FFA nuclear receptors, peroxisome proliferator-activated receptors (PPAR). This is the second revision of a competitive renewal of an RO1 application which continues to study the regulation of the GH axis. The current application centers on the interrelationship between changes in metabolic function and the GH axis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN HORMONE REGULATION OF LHRH BIOSYNTHESIS Principal Investigator & Institution: Petersen, Sandra L.; Associate Professor; Biology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 01-MAR-1992; Project End 31-JUL-2004 Summary: The long-term objective of this research is to determine the mechanism(s) by which estradiol (E2) and progesterone (P4) regulate LHRH biosynthesis and surge release. E2 and P4 differentially regulate two intracellular markers of changes in LHRH neuronal activity in a subpopulation of LHRH neurons--an E2-induced increase in LHRH gene transcription before the onset of LHRH surge release and a P4-dependent increase in Fos expression at the onset of the surge. Because few, if any, LHRH neurons contain estrogen receptors (ER) or progestin receptors (PR), these intracellular events must be mediated by afferent neuronal systems. Recent indirect evidence suggests that noradrenergic (NA) and GABAergic may be these afferent systems. Therefore, in the proposed studies we will test the novel hypothesis that sequential changes in NA and GABAergic signalling directly regulate steroid-specific changes in LHRH synthesis and release and alter intracellular markers of neuronal function. We will first determine whether E2 induces changes in NA release around the time of increased LHRH gene expression. To do this we will assess changes in the activity of brainstem neurons that supply LHRH neurons, and changes in NA turnover rates in the region containing LHRH neurons. We will use dual-label in situ hybridization to determine whether

20

Mifepristone

increases in LHRH gene transcription occur preferentially in neurons with ARs and whether specific AR antagonists can block transcription in these neurons. Finally, we will determine whether ligand-independent activation of PR decreases GABAergic signalling to LHRH neurons, and whether this signal is amplified by administration of P4 and marked by Fos expression. To accomplish this goal, we will test whether RU486 blocks the decline in GABA turnover rates and in levels of glutamic acid decarboxylase (GAD) mRNA previously observed before LHRH surge release, whether P4 furthers these declines, whether changes in GAD mRNA occur preferentially in neurons that also express PR, and whether GABA receptor agonists block the appearance of Fos expression in LHRH neurons. These studies will provide important new information on the identity of the afferent neuronal systems that transduce steroid signals to LHRH neurons. In addition, they win form the basis for future studies on the intracellular mechanisms regulating LHRH biosynthesis and release. This information will be critical for under- standing the neuroendocrine mechanisms controlling ovulation, as well as alterations in these control mechanism that result in precocious puberty, hypothalamic infertility and menopause. Thus, this information will be important for developing safer and more effective contraceptives and therapeutic modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE AFTER TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Stein, Donald G.; Asa G. Candler Professor; Emergency Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: The long-term goal of this revised research proposal is to determine the specific mechanisms by which progesterone mediates neuronal rescue and recovery of function in traumatic brain injury (TBI); the major cause of death in young adults under the age of 35. These findings will be employed in the evaluation of progesterone as a safe and effective treatment for TBI. Progesterone has recently been classified as a neurosteroid because it is also synthesized in astrocytes and oligodendrocytes in the brains of both males and female, where it may play other roles than that of a sex hormone. Previous research has already shown that systemic injection of progesterone in laboratory rats can reduce some of the neuropathological consequences of TBI and enhance behavioral recovery of function. Progesterone treatments reduce cerebral edema dramatically in both males and females when administered within 24 hours of the injury. This is one type of protective effect that can lead to reduced neuronal death and improved functional outcomes. The primary goal of the current proposal is to understand better the physiological mechanisms by which progesterone mediates its neuroprotective actions. We propose a series of 4 Aims using both in vitro and in vivo models of neural injury to determine: (1) if progesterone exerts its effects via its specific receptors. This will be studied by co-administering the hormone with ORG31710, a known progesterone receptor antagonist, or substituting progesterone with an agonist that cannot be metabolized (R5020) in both in vivo and in vitro models of TBI; (2) if, in an in vitro model of injury, progesterone's short-term neuroprotective effects are mediated specifically via sigma receptors; (3) if progesterone will prevent loss of mitochondrial function by reducing oxidative stress initiated in both in vivo and in vitro models of TBI; and (4) if progesterone will reduce the destructive aspects of the inflammatory immune reaction that occurs after TBI. The combination of in vivo and in vitro models will provide parallel evaluation of the mechanisms of progesterone's action. The research proposed here will help to determine whether progesterone can be used as a low-cost, safe and effective therapeutic agent in the acute stages of CNS injury.

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Furthermore, the detailed assessment of progesterone's mechanisms of action will provide a foundation for the intelligent design of artificial therapeutic pharmaceuticals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECRETION

PROGESTERONE

MODULATION

OF

PULSATILE

GNRH

Principal Investigator & Institution: Mccartney, Christopher R.; Center for Res in Reproduction; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): This Research Career Award will support the development of Christopher R. McCartney, M.D., of the University of Virginia (UVa) as he continues to train in patient-oriented research under the mentorship of John C. Marshall, M.D., Ph.D., a renowned researcher in the fields of reproductive neuroendocrinology and the polycystic ovary syndrome (PCOS). This training will allow Dr. McCartney to acquire the knowledge and skills needed by an independent clinical researcher. To this end, the application outlines a career development plan that includes comprehensive instruction in clinical trials methodology, biostatistics, epidemiology, research ethics, assay methodology, and hormone pulse analysis; this will occur in part through the Master of Science Program in the UVa Dept. of Health Evaluation Sciences. Dr. McCartney's research proposal is designed to enhance understanding of the etiology of neuroendocrine abnormalities in PCOS, a very common but enigmatic disorder marked by hyperandrogenism, ovulatory dysfunction, and decreased fertility. Although the etiology of PCOS is unknown, relative gonadotropin-releasing hormone (GnRH) pulse generator resistance to negative feedback by progesterone (P) and estradiol (E2) contributes to a persistently rapid luteinizing hormone (LH) pulse frequency, ovulatory dysfunction, and hyperandrogenemia. GnRH pulse generator resistance to negative feedback may also be present in adolescents with hyperandrogenemia, felt to be a forerunner of adult PCOS; this would, in part, explain the pubertal genesis of abnormal LH secretion in adolescents destined to develop PCOS. The specific goals of this research are to delineate the relative roles of P and E2 in the regulation of the GnRH pulse generator throughout ovulatory menstrual cycles; to elucidate the potential role of P in directing diurnal changes of LH (and by inference GnRH) pulsatility in peripubertal adolescent girls; and to define abnormalities of gonadal steroid feedback on the GnRH pulse generator in hyperandrogenemic adolescents and in adults with PCOS. The research will be performed in a state-of-the-art General Clinical Research Center at UVa and, in conjunction with didactic training in scientific inquiry and data analysis, will permit Dr. McCartney's development into an independent patient-oriented investigator in the field of reproductive endocrinology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE REPRODUCTION

RECEPTOR

A

AND

B

PROTEINS

IN

Principal Investigator & Institution: Conneely, Orla M.; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 30-AUG-2003 Summary: Progesterone plays a central coordinate role in regulation of reproductive events associated with establishment and maintenance of pregnancy including

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Mifepristone

ovulation, uterine and mammary gland development and tumorigenesis and neurobehavioral expression associated with sexual responsiveness. Although most of the downstream molecular and cellular mechanisms by which progesterone exerts these effects are unclear, they are mediated by interaction with intracellular proteins termed progesterone receptors (PR) whose function is to act as ligand activated transcription factors to regulate the expression of specific programs of reproductive target genes. Two PR proteins, termed A and B, that arise from a single gene have been identified in most mammalian species and null mutation of both proteins leads to pleiotropic reproductive abnormalities. Substantial evidence has accumulated in recent years to demonstrate that the A and B proteins display different tissue specific transcription regulatory properties in response to progestin agonists, antagonists and activation of cellular phosphorylation pathways when tested in tissue culture cells. These observations lead us to hypothesise that the physiological responses to progesterone are mediated by the combinatorial actions of two functionally distinct proteins, each of which acts in a differential tissue specific manner to influence the expression of a specific repertoire of target genes. The hypothesis predicts that alterations in the cellular composition of PRs may have significant impact on overall reproductive tissue responsiveness to progesterone and its antagonists including tumorigenic responses of the uterus and mammary gland to PR. To test these predictions we have introduced subtle mutations into the mouse PR gene to selectively ablate expression of the PR A or B proteins and we have generated two novel mutant mouse lines that express only the PRA or PRB proteins from the PR gene. During the second phase of the project, we will use these mutant mouse lines to examine the selective contribution of the PR A and B proteins to PR dependent reproductive function in four areas; 1) ovarian follicular development and fuction; 2) the differentiative and antiestrogenic activities of PR in the uterus; 3) the proliferative and differentiative functions of PR in the mammary gland; and 4) the ligand dependent and independent mechanisms of activation of sexual behaviors mediated by PR in the ventromedial hypothalamus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE RECEPTORS IN BREAST CANCER Principal Investigator & Institution: Horwitz, Kathryn B.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 22-DEC-1979; Project End 30-NOV-2004 Summary: Induction of breast cancers depends on ovarian steroids. However, at diagnosis, 2/3 of tumors have switched, from growth control by steroid agonists, to control by peptide growth factors. Hypothesis: progesterone primes breast cancers for the proliferative effects of growth factors, which then down-regulate progesterone receptors (PR) creating a negative feedback loop. The remaining 1/3 of steroid hormone-dependent tumors respond well to antagonists but acquire resistance as they progress. Hypothesis: acquired resistance to antagonists is associated with inappropriate expression of their agonist effects. Aim 1. Resistance to Agonists. Is steroid resistance biochemically linked to upregulation of growth factor signaling? Using stable cell lines expressing A- or B-isoforms of PR, or mutant PR, we will study priming effects of progesterone and the antiprogestin RU486: on acquired sensitivity to proliferative effects of EGF; on upregulation of MAPK and STAT signaling; on MAPK phosphorylation of PR which targets them for ubiquitylation and downregulation; on transcriptional synergism at p21 and c-fos promoters. These studies will define mechanisms for cross-talk between PR and EGF in the cytoplasm and nucleus. Aim 2.

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Acquired Resistance to Anatagonists. Are the agonist effects of mixed antagonists upregulated by recruitment of regulatory proteins to antagonist-occupied PR? Three novel proteins have been isolated in an antagonist-biased yeast two hybrid screen. ORF number 93 has multiple NR boxes and at least 3 TPR domains. We will clone it, and ask whether it acts as a scaffold to assemble PR in a multi-protein complex with EGF signaling molecules; is a coregulator; or assembles PR into a repressive transcription complex. The mechanisms of two other novel proteins will be assessed. These studies will describe the function of antagonist-occupied receptors as governed by three new receptor- interacting proteins. Aim 3. Acquired Resistance to Antagonists: Breast Cancers. Does the transcriptional coactivator to corepressor ratio determine outcome to tamoxifen? Tumors from tamoxifen responsive or resistant patients will be measured for transcript expression of the coactivators L7/SPA and SRC-1, and the corepressors NCoR and SMRT, in relation to treatment response. We will show that mechanisms of SMRT repression are novel. Other studies address EGF signaling molecules and ORF number 93. These studies will document the relationships between coregulators and tamoxifen resistance, and demonstrate that antagonist-occupied steroid receptors recruit factors inappropriately. Overall, these studies will explain hormone-resistance mechanisms in breast cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED CONTROL TRIAL OF MIFEPRISTONE FOR FIBROIDS Principal Investigator & Institution: Fiscella, Kevin; Associate Director; Family Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Background: Uterine fibroids represent the leading indication for roughly 600,000 hysterectomies performed annually in the United States. There is no satisfactory long-term medical therapy for fibroids, which disproportionately affect black women. Preliminary data from our open label study show that oral administration of mifepristone 5 mg per day is associated with significant improvement in fibroid symptoms and nearly 50% reduction in fibroid size. However, findings from this study were limited by absence of a placebo control group, absence of blinding, and absence of a validated, disease-specific quality of life outcome measure. Aims: We propose a six-month randomized, double-blinded, placebocontrolled trial of low-dose mifepristone. Seventy women with moderate to severely symptomatic fibroids, confirmed by ultrasonography, will be randomly allocated to receive mifepristone 5 mg per day or an identical appearing placebo. The primary outcome measure will be change in disease-specific quality of life based on the recently validated Uterine Fibroid Symptom Quality of Life questionnaire. Secondary outcomes include change in global health status, fibroid size, pain, bleeding, and adverse effects including endometrial hyperplasia. We also propose to test the hypothesis that administration of mifepristone will be associated with significant reductions in fibroid blood flow, which in turn, will be associated with reductions in fibroid volume. Significance: The study offers the promise for a safe, effective medical treatment for symptomatic fibroids that could potentially benefit millions of women world-wide, prevent thousands of hysterectomies and reduce health care costs. The study may also offer valuable insight into a mechanism by which mifepristone reduces fibroid size. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATABLE GENE TRANSFER SYSTEM Principal Investigator & Institution: Tsai, Sophia Y.; Professor; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: Human LDL receptor is expressed primarily in the liver and functions to clear the LDL and cholesterol from the circulation. Mutations of the LDL receptor have been shown to cause hypercholesterolemia which often results in cardiovascular diseases and myocardial infarction at an early age. The goal of this project is to use an inducible system to specifically target the human LDL receptor to the liver in transgenic mice as well as to study the efficacy of using adenoviral vector to deliver this inducible system into cell culture. The inducible system consists of a chimeric transcriptional regulator GLVP and a target gene containing the binding sites recognized by the regulator. In the presence of an inducer, RU486, the regulator binds and activates target gene expression. This inducible system has previously been demonstrated to effectively induce the expression of various target genes in cell culture and transgenic mice up to 5000-fold. To investigate controlled expression of human LDL receptor, we propose to: 1). Generate transgenic mouse target lines containing the human LDL receptor- cDNA; 2). Generate bitransgenic mouse lines capable of expressing the human LDL receptor in response to exogenous ligand; 3). Modify the regulator by substituting the viral activation domain with an activation domain from a human transcription factor to facilitate the future application of this inducible system for gene therapy; 4). Inducible expression of the LDL receptor in cultured cells using adenoviral delivery system. These studies are crucial in providing us with important kinetic data on LDL receptor expression and clearance of serum LDL and cholesterol. We expect that the results from this investigation shall enable us to formulate better protocols for future human gene therapy study in hypercholesterolemia and other cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATED GENE EXPRESSION AND DROSOPHILA BEHAVIOR Principal Investigator & Institution: Davis, Ronald; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Experiments are proposed to develop a molecular genetic system in Drosophila for regulating the activity of transgenes in both time and space. This technology is particularly needed for use in conjunction with forward genetics to determine the developmental time and the tissue-specific expression pattern required for any given gene. It is of particular interest for the molecular genetic analysis of behavior. An innocuous inducing reagent will be used to turn on the activity of a specific transcription factor expressed transgenically behind cell-type specific promoters. Other transgenes made to be responsive to the transcription factor will therefore be turned on by the inducer in only those cells in which the transcription factor is expressed. Experiments are proposed to test the system by rescuing a Drosophila memory mutant by expressing the normal gene carried on a transgene in both time and in space. Furthermore, lethal mutants in genes potentially important for learning will be rescued by providing expression of the normal gene only during development. The techniques proposed here offer a general method for turning on gene activity both spatially and temporally in Drosophila. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF ATPASE II AND CLEARANCE OF CANCER CELLS Principal Investigator & Institution: Banerjee, Probal; Assistant Professor; Chemistry; College of Staten Island Staten Island, Ny 10314 Timing: Fiscal Year 2004; Project Start 01-MAY-1998; Project End 30-APR-2007 Summary: (provided by applicant): In the natural process known as phagocytosis a multicellular organism removes unwanted or injured cells with the help of scavenger cells, termed phagocytes. Such phagocytic cells, e.g. the macrophages in the peripheral system and the microglia in the brain, specifically bind to the dying cells through certain cell-surface molecules, one of which is phosphatidylserine (PS). PS, which normally resides in the inner-leaflet of the plasma membrane, flip flops to the outer leaflet in the dying cells and is recognized by PS receptors located on phagocytic cells. In healthy cells a bifunctional enzyme, which is both a Mg2+-/-ATPase and also an aminophospholipid translocase (APTL), translocates PS to the inner leaflet of the plasma membrane. This process apparently overrides the effect of two other enzymes, the scramblase (which bidirectionally translocates all phospholipids molecules) and the floppase (which very slowly translocates phospholipids from the inner leaflet to the outer). Many earlier studies have shown that offsetting the balance among APTL, scramblase, and floppase by inhibiting APTL results in externalization of PS and phagocytosis. A P-type ATPase, ATPase II, bears striking similarity in properties to APTL and transfection of antisense ATPase II cDNA causes externalization of PS. Expression of ATPase II mRNA shows tissue-specificity, with the highest levels of expression observed in the brain and the skeletal muscle. We have isolated the ATPase II promoter and showed that it displays considerable tissue specificity in luciferase reporter assays. In our current project we will further analyze the promoter of the ATPase II gene to study the sequence elements that confer this cell type-specificity of expression. Also, in our earlier studies, we had observed that stable overexpression of ATPase II causes appearance of mixed, voltagegated calcium channels in a hippocampal neuron-derived cell line, HN2, which normally does not display any calcium current. In parallel, induced expression of the channel-forming subunit, (1B, of the N-type channels was also observed. We will prepare and test an inducible expression system for ATPase II in the HN2 cells in order to verify if this induced expression of calcium channels was due to transactivated gene expression or a protein-protein interaction between ATPase II and the calcium channel proteins. Finally, since antisense ATPase II transfection causes externalization of PS molecules, we will use this concept to design and test a novel strategy of removing cancer cells through phagocytosis without attempting to kill them with antimetabolites. In this strategy we will selectively ablate ATPase II expression in the cancer cells by using ATPase II-specific small inhibitory RNA (siRNA). Selective expression of the siRNA in cancer cells will be achieved through the use of a promoter for a highly cancer cell-selective protein, e.g. the (1-6 N acetyl glucosaminyl transferase V (GnT-V). Abrogation of ATPase II in the cancer cells would cause PS externalization and phagocytic removal of these cells. Studying the mechanism of ATPase II expression, analyzing its role in the induction of calcium channels, and evaluating its use in designing a new strategy for the removal of cancer cells will be the overall goal of our project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF SLO SPLICING IN THE UROGENITAL SYSTEM Principal Investigator & Institution: Davies, Kevin P.; Urology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2004; Project Start 10-APR-2004; Project End 31-MAR-2007

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Mifepristone

Summary: (provided by applicant): Dr. Kevin Davies has several years of experience as a molecular biologist. He has recently entered a new field of study, Urology. This K01 application will allow him to gain experience in the basic concepts of urogenital physiology. He will then be in an ideal position to apply the techniques of molecular biology to fundamental problems in the filed of Urology as an independent researcher. The Dept. of Urology at Albert Einstein College of Medicine is an excellent environment to gain experience in urogenital physiology. It has an active multi-disciplinary research group, which includes leaders in the filed of Urology, such as Dr, Arnold Melman and Dr. George Christ. The Dept conducts both clinical and basic research, and is active in translating this work from the laboratory to clinical therapies. In order to gain experience in urogenital physiology this research project will investigate the effect of hormones on splicing of the Slo gene in urogenital smooth muscle tissue in vivo and in vitro. Our working hypothesis is that SIo isoform expression in smooth muscle myocytes is modulated by hormones, and moreover, that these changes in isoform expression are relevant to urogenital physiology/dysfunction. Specifically we will look at the effects of hormones (stress axis hormones and sex hormones on the splicing of the Slo gene in female rats in vivo. Changes in the splicing of the Slo gene will be monitored in the smooth muscle tissue of these animals (aorta, colon, bladder and vagina). The different splice forms of the Slo gene will be characterized for their cellular and physiological function. In addition, a reporter construct will be developed which will allow real time analysis of splicing in cultured rat smooth muscle cells (aorta, colon, bladder and vagina). The ability of hormones to effect splicing in this in vitro system will be analyzed, as well as investigations into the signaling pathways that determine Slo splicing. This research project will allow Dr. Davies to develop a thorough understanding of urogenital physiology, while at the same time allowing him to utilize his experience in molecular biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RU 486 AND GLUCOSE METABOLISM Principal Investigator & Institution: Tayek, John A.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STEROID ANTAGONISTS AND RESISTANCE IN BREAST CANCER Principal Investigator & Institution: Edwards, Dean P.; Professor; Pathology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 28-FEB-2003 Summary: Steroid receptors antagonists are used for a variety of clinical purposes including treatment of breast cancer and other hormone- dependent tumors. It has become increasingly apparent that the cellular level of the steroid receptor and the antagonist are not the only factors that determine biological response. Steroid receptor interaction with co-regulatory proteins such as co-activators, co-repressors and other transcription factors are important determinants of the final receptor activity. Because steroid receptor antagonists exhibit varying degrees of hormone agonist activity dependent on cell/tissue type and physiological state of the cell, we hypothesize that the relative agonist/antagonist activity exhibited by these compounds is controlled by

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the cellular level of expression, or availability, of these other receptors interacting proteins. The overall goal of this research is to identify functionally important receptorinteracting proteins and protein complexes that contribute to steroid antagonists behaving as effective antagonists in some cell/tissue types and physiological states, and as hormone agonists in others. Our research will focus on progesterone receptor (PR) and progesterone antagonists. We expect that many of the fundamental mechanisms discovered with PR will apply to other receptors such as estrogen (ER), androgen (AR) and glucocorticoid receptors (GR). AIM #1 of the proposal will biochemically isolate and identify functionally important receptor interacting co-activator and co-repressor interacting co-activator and co-repressor complex that correlate with antagonists exhibiting partial agonist activity in different cell types and under different physiological states. AIM #2 will use a genetic screening strategy to identify other receptor interacting co-regulatory proteins involve din mediating hormone agonist activities of antagonists. AIM #3 will investigate how steroid antagonists alter receptor interaction with specific co-regulatory proteins to either successfully inactive the receptor or leave it in an active state. AIM #4 will determine how steroid antagonists influence receptor interaction with other physiologically important gene regulatory proteins. As an example of this mode of regulation, PR co- expression of STAT5 (signal transducers and activators of transcription) mediated activation of milk protein gene expression will be investigated. An understanding of steroid receptor antagonist action at this mechanistic level is anticipated to help in the design of new receptor antagonists (or hormone mimics) that will elicit the desired cell/tissue specific therapeutic response without adverse responses in other tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOXICITY

STEROID

AS

CYTOPROTECTANTS

AGAINST

OXIDATIVE

Principal Investigator & Institution: Chen, Qin M.; Associate Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Stress is known to cause an increase in the synthesis of corticosteroids by the adrenal glands. Although corticosteroids have been shown to contribute to the pathophysiology of suppressed Immune response and a number of psychiatric disorders, the effect of CT on the heart remains unclear. Doxorubicin (Dox) is an anti-neoplastic drug that can produce chronic cardiac toxicity which is manifested as dilated cardiomyopathy. An important feature of this form of cardiomyopathy is the apoptosis of cardiomyocytes. Our preliminary studies found that corticosterone (CT) pretreatment prevented Dox from inducing apoptosis of cardiomyocytes. The glucocorticoid receptor antagonist mifepristone prevented CT from inducing a cell survival response. Several forms of g!ucocorticoids, aldosterone, progesterone and retinoic acid but not estrogen, testosterone or L-thyroxin can inhibit apoptosis of cardiomyocytes. Analyses of ERK, Akt and SGK-1 activities or bcl-2 expression indicated that CT neither activated the known survival kinases nor elevated the expression of the anti-apoptotic gene bcl- 2. The conditioned medium of CT-treated cardiomyocytes shows partially cytoprotective effective. The TranSignal array approach found that CT treatment could potentially activate 21 transcription factors. We hypothesize that activation of the glucocorticoid receptor initiates transcriptional activation of survival genes in cardiomyocytes in vitro and in vivo. Specific aims of this grant include: 1) To test if CT binding causes its receptor to interact with and to activate multiple transcription factors in cardiomyocytes; 2) To test that the activation of cell

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survival genes contributes to CT-induced cytoprotection; and 3) To demonstrate that CT protects the heart from cardiomyopathy induced by Dox in vivo via inducing the transcription of cell survival genes. This project will combine our expertise in genomics, transcriptomics and proteomics to systematically study the linkage between the glucocorticoid receptor and cell survival mechanisms. Given the fact that stress is unavoidable in our daily life, this project will provide novel information to advance our understanding in the biological effect of corticosteroids on the heart. More importantly, since apoptosis has been shown to contribute to heart failure induced by the chemotherapy agent Dox as well as by many forms of cardiovascular disease, our finding and proposed mechanistic study will provide a hope for novel therapy against heart failure in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE AND FUNCTION OF THE HUMAN PREGNANE X RECEPTOR Principal Investigator & Institution: Redinbo, Matthew R.; Biochemistry and Biophysics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: The orphan nuclear pregnane X receptor (PXR) regulates the expression of numerous genes vital to xenobiotic and bile acid metabolism. Such genes include cytochrome P450-3A4, which metabolizes greater than 50 percent of human drugs, and the drug efflux pump MDR1. In contrast to most nuclear receptors, PXR is promiscuous and responds to a wide variety of structurally- diverse drugs and endogenous compounds. To unravel the structural basis of PXR's promiscuity and function, we determined crystal structures of the ligand binding domain of human PXR (hPXR) by itself and in complex with the cholesterol-lowering drug SR12813. hPXR has a novel nuclear receptor fold and contains a large, elliptical ligand binding pocket. Surprisingly, this pocket allows SR12813 to bind in three orientations at once -- a direct observation of binding promiscuity. These results provide a structural framework for further examination of this receptor. We are now poised to address two fundamental questions regarding PXR. First, how does this single protein respond to such a wide variety of distinct compounds? Second, how does PXR mediate the signal to activate transcription? The goals of these investigations are to elucidate PXR's role in molecular endocrinology and drug metabolism, and to facilitate the development of novel methods for drug screening involving PXR. Four hypotheses will be tested: - The positioning of PXR surface residues and the binding of the co-activator SRC-1 to PXR mediate transcriptional activation by stabilizing a particular conformation of the receptor. - PXR uses shuffled polar interactions to allow small ligands to bind in multiple orientations. PXR changes in structure to accommodate large ligands. - Polar residues in the ligand binding pocket of PXR dictate the "directed promiscuity" exhibited by PXRs across species. Six specific aims will be pursued using the tools of x-ray crystallography, molecular biology and biochemistry: 1. Determine crystal structures of hPXR in complex with fragments of the transcriptional co-activator SRC-1. 2. Examine structures of hPXR variants containing surface changes known to affect its ability to activate transcription. 3. Unravel PXR's promiscuity by examining mutations designed to impact the binding of SR12813. 4. Determine structures of hPXR in complexes with small drugs and endogenous compounds. 5. Elucidate structures of hPXR in complexes with large drugs like rifampicin and taxol. 6. Examine structures of mouse and rabbit PXR to determine why different species respond to distinct xenobiotics.

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

Project Title: SUPPRESSION OF BREAKTHROUGH BLEEDING IN LNG-IUS USERS Principal Investigator & Institution: Brenner, Robert M.; Senior Scientist; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The Mirena(c) (Leiras, OY, Finland) is an intrauterine system (IUS) that releases levonorgestrel (LNG) and provides women with highly effective contraception for 5 years. However, serious breakthrough bleeding (BTB) can occur that leads many patients to discontinue treatment. In women using subcutaneous Norplant contraception, BTB can be suppressed by intermittent antiprogestin therapy with mifepristone. NICHD has a new antiprogestin, CDB-2914, that is more potent than mifepristone. The goal of this proposal is to determine whether CDB-2914 can suppress the BTB associated with the LNG-IUS. Preclinical studies will be done first in rhesus macaques fitted with an LNG-IUS and the information gained will be transmitted to Professor Hilary Critchley, University of Edinburgh, who will select a test population of 150 women from a pool of over 400 who are being fitted annually with an LNG-IUS for contraception. The bleeding-suppressive dose and schedule of CDB-2914 that works well in macaques will be adapted for use in women. The work consists of two major aims: Aim 1: to establish an effective, bleeding-suppressive dose schedule of CDB 2914 in macaques, and to assess spatio-temporal expression of bleeding-associated factors in the endometrium. Aim 2: to conduct a randomized, placebo controlled trial to evaluate CDB-2914 suppression of BTB in women being fitted with the LNG-IUS; and for added value, to develop a questionnaire to assess acceptability of the proposed treatment to women. This proposal involves translation of the information gained from basic research with macaques into clinical practice in women within the time frame of the grant. It is essential to conduct the clinical work at the University of Edinburgh, Scotland, UK, because no clinic in the USA has such a large patient population of women being fitted with the LNG-IUS for contraception. The macaque model provides excellent predictability for human studies, and Drs. Brenner and Critchley have published collaboratively on data from macaques and women in several recent papers. The proposal brings basic scientists and clinicians together for a "bench to bedside" approach that will advance women's health and improve contraceptive technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURVIVAL SIGNALING IN BREAST CANCER Principal Investigator & Institution: Conzen, Suzanne D.; Assistant Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 11-MAY-2001; Project End 30-APR-2006 Summary: Suzanne Conzen, M.D., recieved a balaurate degree, magna cum laude from Brown University, Her first exposure to bench science was in Dr. Charles Janeway, Jr's labortory at Yale Medical School. Following her second year of medical school she obtained an M.Sc. At the University of Tropical Medicine and Science before graduating from Yale in 1987. Following an internal medince residency at Cornell Medical Center she did her hematology and oncology fellowships at Dartmounth. Dr. Conzen wa awarded a Howard Hughes Physician Fellowship to study mechanism OS Sv40 mediated transformation in the Dartmouth Biochemistry under the mentorship of Dr.

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Chuck Cole. Dr. Conzen then moved to the University of Chicago's Ben May Institute to do a postdoctoral fellowship in the labortory of Dr. Nauseam Hay where she studied tumor-associated mutant c-Myc-medication apoptosis andd cell cycle progression. In 1998 Dr. Conzen was appointed Assistant Prefacer at the University of Chicago and established a research program studying mammary epithelial cell survival under the mentioship of Dr. Geoffrey Greene, director of the Breast Cancer Program at the Inversed of Chicago Cancer Cent. Dr. Conzen's work has shown that the glucocorticoid receptor (GR) has potent signaling effects in mammary epithelium and can transcriptionaly activate cell cycle-related kinases hypothesized to be important for cell survival and division. Because Dr. Conzen has little previous experience in steriod receptor biology or the analysis of intracelluar kinnase-mediated signaling pathways, the proposed research career development plan requests support to provide a comprehensive training period to work closely with Drs. Greene andd Marsha Rosner to determine the mechanism of GR- medicated survival signaling in breast cancer. Dr. Conzen proposes to characterize the gluocorticoid repersiveness and GR alpha and beta expression in breast tumor cell lines and to conurrently investigate the signaling pathways of GR-induced or repressed cellular kinase including SGK( serum and glucocorticoid induible kinases). Under the mentorship of Dr. Greene and with the assistance of Dr. Shutsung Liao and Dr. Mark Ratain, Dr. Conzen also proposes to eastablish anddan in vivo system to evaluate the GR in human breast cancer using an ER/PR negative human mammary carsinoma xenograft nude mouse model. The proposed career development plan will formulize Dr. Conzen's mentoring program with a defined research plan and ensure the protected research time needed for training in the methods and anyalytical skills required to develop an independent research program in survival signaling in malignant and normal breast epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WESTERN REGIONAL COMMUNITY CLINICAL ONCOLOGY PROGRAM Principal Investigator & Institution: King, David K.; Banner Good Samaritan Medical Center Phoenix, Az 85006 Timing: Fiscal Year 2002; Project Start 01-SEP-1983; Project End 31-MAY-2003 Summary: The Greater Phoenix Community Clinical Oncology Program (GPCCOP)is a consortium of five hospitals with 67 investigations led by principal investigator David K. King, M.D. Dr. King and many of the investigators have been associated with the CCOP since its initial planning stage in 1982. The continuing long-term goals and specific aims of the GPCCOP include: 1) increased clinical research activities; 2) access to additional clinical trials; 3) further development of cancer control research initiatives and patient accrual; 4) maintenance of quality data management; 5) pharmacy resources to coordinate and manage drug distribution; 6) involvement of primary care physicians in state-of-the- art cancer management and education; and 7) continued development of data management systems to support NCI evaluations. GPCCOP's organizational structure requires the involvement of the Co- Principal Investigators and hospital administrators from each of the participating institutions in the planning and policymaking decisions of the CCOP. The physicians, nurses and administrative staff have active roles in guiding the GPCCOP toward attainment of its goals. This experienced team has demonstrated their commitment and ability to accrue patients to both therapeutic and cancer control protocols while maintaining high levels of quality control and timely submissions. GPCCOP's data management systems were recognized by SWOG in 1991 with the Outstanding Achievement Award. Additional investigators,

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specializing in medical and radiation oncology, have been recruited to the GPCCOP to ensure the availability of total patient care for the 3000 average new patients seen each year. By adding investigators from the Tucson area and adding the GOG as a research base, a higher level of participation is expected. The above resources, the placement of 347 patients on treatment protocols and 1097 patients on cancer control trials during the period 1989 to present demonstrate GPCCOP's preparedness to continue its active participation in NCI's Community Oncology Program. 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 “mifepristone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for mifepristone in the PubMed Central database: •

Embryonic abnormalities at medical termination of pregnancy with mifepristone and misoprostol during first trimester: observational study. by Blanch G, Quenby S, Ballantyne ES, Gosden CM, Neilson JP, Holland K.; 1998 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28572

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 mifepristone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “mifepristone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for mifepristone (hyperlinks lead to article summaries): 3 4

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. 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 comparative analysis of fall in haemoglobin following abortions conducted by mifepristone (600 mg) and vacuum aspiration. Author(s): Thonneau P, Poirel H, Fougeyrollas B, Maria B, Meyer L, Goepp A, Hercberg S, Spira A. Source: Human Reproduction (Oxford, England). 1995 June; 10(6): 1512-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7593526

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A comparison of 600 and 200 mg mifepristone prior to second trimester abortion with the prostaglandin misoprostol. Author(s): Webster D, Penney GC, Templeton A. Source: British Journal of Obstetrics and Gynaecology. 1996 July; 103(7): 706-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8688400

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A comparison of medical abortion (using mifepristone and gemeprost) with surgical vacuum aspiration: efficacy and early medical sequelae. Author(s): Henshaw RC, Naji SA, Russell IT, Templeton AA. Source: Human Reproduction (Oxford, England). 1994 November; 9(11): 2167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7868693

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A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone. Author(s): Berthois Y, Salat-Baroux J, Cornet D, De Brux J, Kopp F, Martin PM. Source: Fertility and Sterility. 1991 March; 55(3): 547-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1900480

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A pilot study of mifepristone in combination with sublingual or vaginal misoprostol for medical termination of pregnancy up to 63 days gestation. Author(s): Hamoda H, Ashok PW, Dow J, Flett GM, Templeton A. Source: Contraception. 2003 November; 68(5): 335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636936

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A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary. Author(s): Martin CW, Brown AH, Baird DT. Source: Contraception. 1998 August; 58(2): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773264

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A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone. Author(s): Tang OS, Lee SW, Ho PC. Source: Human Reproduction (Oxford, England). 2002 November; 17(11): 2865-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407040

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A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Author(s): Jain JK, Dutton C, Harwood B, Meckstroth KR, Mishell DR Jr. Source: Human Reproduction (Oxford, England). 2002 June; 17(6): 1477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042265

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A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation. Author(s): Tang OS, Chan CC, Ng EH, Lee SW, Ho PC. Source: Human Reproduction (Oxford, England). 2003 November; 18(11): 2315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585880

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A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception. Author(s): Ashok PW, Stalder C, Wagaarachchi PT, Flett GM, Melvin L, Templeton A. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 May; 109(5): 553-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12066946

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A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. Author(s): Bartley J, Baird DT. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 November; 109(11): 1290-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452468

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A randomised study of two doses of gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. Author(s): Thong KJ, Lynch P, Baird DT. Source: Contraception. 1996 August; 54(2): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8842586

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A randomized clinical trial of mifepristone (RU486) for induction of delayed menses: efficacy and acceptability. Author(s): Grimes DA, Mishell DR Jr, David HP. Source: Contraception. 1992 July; 46(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1424618

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A randomized comparative study on mifepristone alone and in combination with tamoxifen for emergency contraception. Author(s): Changhai H, Youlun G, Jie Y, Bingshun W, Exiang Z, Ersheng G, Mauck C. Source: Contraception. 2002 October; 66(4): 221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413615

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A randomized comparison of mifepristone and self-administered oral or vaginal misoprostol for early abortion. Author(s): Aubeny E, Chatellier G. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2000 September; 5(3): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11131781

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A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Author(s): Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA; MOD Study Trial Group. Source: Obstetrics and Gynecology. 2004 May; 103(5 Pt 1): 851-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15121556

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A randomized double-blind comparison of two single doses of mifepristone for emergency contraception. Author(s): Xiao BL, Von Hertzen H, Zhao H, Piaggio G. Source: Human Reproduction (Oxford, England). 2002 December; 17(12): 3084-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456607

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A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Author(s): Tang OS, Gao PP, Cheng L, Lee SW, Ho PC. Source: Human Reproduction (Oxford, England). 1999 March; 14(3): 722-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221703

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A single dose of mifepristone (200 mg) in the immediate preovulatory phase offers contraceptive potential without cycle disruption. Author(s): Brown A, Williams A, Cameron S, Morrow S, Baird DT. Source: Contraception. 2003 September; 68(3): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561541

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A study of the effect of mifepristone (antiprogesterone) followed by prostaglandin on uterine activity and fetal heart rate in patients having a termination of pregnancy. Author(s): Pulkkinen MO, Piiroinen O, Vainikka J. Source: Archives of Gynecology and Obstetrics. 1989; 244(2): 75-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2712600

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A two-stage increase in the dose of misoprostol improves the efficacy of medical abortion with mifepristone and prostaglandins. Author(s): Aubeny E. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2001 March; 6(1): 54-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11334477

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Abortion with mifepristone and misoprostol: regimens, efficacy, acceptability and future directions. Author(s): Newhall EP, Winikoff B. Source: American Journal of Obstetrics and Gynecology. 2000 August; 183(2 Suppl): S4453. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10944369

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Abortion, revised: participants in the U.S. clinical trials evaluate mifepristone. Author(s): Simonds W, Ellertson C, Springer K, Winikoff B. Source: Social Science & Medicine (1982). 1998 May; 46(10): 1313-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9665563

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Acceptability and feasibility of early pregnancy termination by mifepristonemisoprostol. Results of a large multicenter trial in the United States. Mifepristone Clinical Trials Group. Author(s): Winikoff B, Ellertson C, Elul B, Sivin I. Source: Archives of Family Medicine. 1998 July-August; 7(4): 360-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9682690

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Acceptability of mifepristone for early pregnancy interruption. Author(s): David HP. Source: Law Med Health Care. 1992 Fall; 20(3): 188-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11643042

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Acceptability of suction curettage and mifepristone abortion in the United States: a prospective comparison study. Author(s): Jensen JT, Harvey SM, Beckman LJ. Source: American Journal of Obstetrics and Gynecology. 2000 June; 182(6): 1292-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10871441

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Acetaminophen as a pain enhancer during voluntary interruption of pregnancy with mifepristone and sulprostone. Author(s): Weber B, Fontan JE. Source: European Journal of Clinical Pharmacology. 1990; 39(6): 609. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2095349

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Action of mifepristone on the expression of insulin-like growth factor binding protein-1 mRNA and protein during the early luteal phase in the human oviduct. Author(s): Qiu X, Sun X, Christow A, Stabi B, Gemzell-Danielsson K. Source: Fertility and Sterility. 2003 September; 80 Suppl 2: 776-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505753

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Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells. Author(s): El Etreby MF, Liang Y, Wrenn RW, Schoenlein PV. Source: Breast Cancer Research and Treatment. 1998 September; 51(2): 149-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9879777

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Advanced cervical pregnancy: uterus-sparing therapy initiated with a combination of methotrexate and mifepristone followed by evacuation and local hemostatic measures. Author(s): Heikinheimo O, Leminen A, Cacciatore B, Rutanen EM, Kajanoja P. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2004 February; 83(2): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14756743

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Alterations in sex steroids and gonadotropins in post-menopausal women subsequent to long-term mifepristone administration. Author(s): Heikinheimo O, Ranta S, Grunberg S, Spitz IM. Source: Steroids. 2000 October-November; 65(10-11): 831-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108895

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Alterations in the pituitary-thyroid and pituitary-adrenal axes--consequences of longterm mifepristone treatment. Author(s): Heikinheimo O, Ranta S, Grunberg S, Lahteenmaki P, Spitz IM. Source: Metabolism: Clinical and Experimental. 1997 March; 46(3): 292-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9054472

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Alternatives to mifepristone regimens for medical abortion. Author(s): Pymar HC, Creinin MD. Source: American Journal of Obstetrics and Gynecology. 2000 August; 183(2 Suppl): S5464. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10944370

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An open label trial of C-1073 (mifepristone) for psychotic major depression. Author(s): Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF. Source: Biological Psychiatry. 2002 September 1; 52(5): 386-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242054

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Analysis of 369 abortions conducted by mifepristone (RU486) associated with sulprostone in a French family planning center. Author(s): Thonneau P, Fougeyrollas B, Spira A. Source: Fertility and Sterility. 1994 April; 61(4): 627-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7512053

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Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice. Author(s): El Etreby MF, Liang Y, Johnson MH, Lewis RW. Source: The Prostate. 2000 February 1; 42(2): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617866

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Approval of mifepristone (RU 486) in Europe. Author(s): Sitruk-Ware R. Source: Zentralblatt Fur Gynakologie. 2000; 122(5): 241-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10857210

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Are prostaglandins mediators of mifepristone (RU 486)-induced cervical softening in early pregnancy? Author(s): Radestad A, Bygdeman M. Source: J Lipid Mediat. 1993 March-April; 6(1-3): 503-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8358009

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Are US health professionals likely to prescribe mifepristone or methotrexate? Author(s): Koenig JD, Tapias MP, Hoff T, Stewart FH. Source: J Am Med Womens Assoc. 2000; 55(3 Suppl): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10846327

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Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometrium. Author(s): Papp C, Schatz F, Krikun G, Hausknecht V, Lockwood CJ. Source: Early Pregnancy. 2000 October; 4(4): 230-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11742418

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Bleeding patterns after early abortion with mifepristone and misoprostol or manual vacuum aspiration. Author(s): Davis A, Westhoff C, De Nonno L. Source: J Am Med Womens Assoc. 2000; 55(3 Suppl): 141-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10846324

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Blood loss following induction of early abortion using mifepristone (RU 486) and a prostaglandin analogue (gemeprost). Author(s): Rodger MW, Baird DT. Source: Contraception. 1989 October; 40(4): 439-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2582769

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Blood loss in termination of early pregnancy by vacuum aspiration and by combination of mifepristone and gemeprost. Author(s): Chan YF, Ho PC, Ma HK. Source: Contraception. 1993 January; 47(1): 85-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8436004

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Blood loss in termination of early pregnancy with mifepristone and gemeprost. Author(s): Prasad RN, Choolani M, Roy A, Ratnam SS. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1995 August; 35(3): 329-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8546658

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Blood loss with mifepristone--misoprostol abortion: measures from a trial in China, Cuba and India. Author(s): Harper C, Winikoff B, Ellertson C, Coyaji K. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1998 October; 63(1): 39-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9849710

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Can vaginal misoprostol be administered 1 to 3 days after mifepristone without loss of efficacy or an increase in adverse events? Author(s): Richardson CR. Source: The Journal of Family Practice. 2001 January; 50(1): 9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195490

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Cervical mucus concentration of prostaglandins E2 and F2 alpha after pretreatment with mifepristone in the first trimester of pregnancy. Author(s): Bokstrom H, Norstrom A, Wiqvist N. Source: Prostaglandins. 1995 January; 49(1): 41-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792390

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Cervical pregnancy successfully treated with a sequential combination of methotrexate and mifepristone. Author(s): Sexton C, Sharp N. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 May; 42(2): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12069153

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Cervical ripening with mifepristone (RU 486) in first trimester abortion. An electron microscope study. Author(s): Radestad A, Thyberg J, Christensen NJ. Source: Human Reproduction (Oxford, England). 1993 July; 8(7): 1136-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8408500

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Cervical ripening with mifepristone before labor induction: a randomized study. Author(s): Giacalone PL, Targosz V, Laffargue F, Boog G, Faure JM. Source: Obstetrics and Gynecology. 1998 October; 92(4 Pt 1): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9764616

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Cervical smooth muscle contractile activity after treatment with mifepristone and progesterone. Author(s): Bokstrom H, Norstrom A, Rdestad A. Source: Contraception. 1994 February; 49(2): 115-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8143451

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Challenges to the FDA approval of mifepristone. Author(s): Calhoun BC, Harrison DJ. Source: The Annals of Pharmacotherapy. 2004 January; 38(1): 163-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742814

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Changes in adrenergic receptors in the pregnant human uterine cervix following mifepristone or placebo treatment in the first trimester. Author(s): Kovacs L, Falkay G. Source: Human Reproduction (Oxford, England). 1993 January; 8(1): 119-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8458913

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Changes in circulating alphafetoprotein following administration of mifepristone in first trimester pregnancy. Author(s): Chard T, Olajide F, Kitau M. Source: British Journal of Obstetrics and Gynaecology. 1990 November; 97(11): 1030-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1701323

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Mifepristone

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Circulating concentrations of the antiprogestins CDB-2914 and mifepristone in the female rhesus monkey following various routes of administration. Author(s): Larner JM, Reel JR, Blye RP. Source: Human Reproduction (Oxford, England). 2000 May; 15(5): 1100-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10783360

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Circulating levels of placental protein 14 and progesterone following Mifepristone (RU38486) and Gemeprost for termination of first trimester pregnancy. Author(s): Howell RJ, Olajide F, Teisner B, Grudzinskas G, Chard T. Source: Fertility and Sterility. 1989 July; 52(1): 66-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2744189

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Clinical pharmacokinetics of mifepristone. Author(s): Heikinheimo O. Source: Clinical Pharmacokinetics. 1997 July; 33(1): 7-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9250420

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Clinical trials with RU 486 (mifepristone): an update. Author(s): Ulmann A, Dubois C. Source: Acta Obstetricia Et Gynecologica Scandinavica. Supplement. 1989; 149: 9-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2694739

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Clinical use of mifepristone (RU 486). Author(s): Baird DT. Source: Annals of Medicine. 1993 February; 25(1): 65-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8435192

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Clinical uses of mifepristone (MFP). Author(s): Ulmann A, Peyron R, Silvestre L. Source: Annals of the New York Academy of Sciences. 1995 June 12; 761: 248-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7625724

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Clinical uses of mifepristone: an update for women's health practitioners. Author(s): Beal MW, Simmonds K. Source: Journal of Midwifery & Women's Health. 2002 November-December; 47(6): 45160. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484667

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Clinicians' perception of sonogram indication for mifepristone abortion up to 63 days. Author(s): Fielding SL, Schaff EA, Nam NY. Source: Contraception. 2002 July; 66(1): 27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169378

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Collaborative research and development on mifepristone in China to reduce unwanted pregnancies and recourse to abortion. Author(s): Duncan GW. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 December; 67 Suppl 2: S69-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10661743

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Combined estimates of effectiveness of mifepristone 10 mg in emergency contraception. Author(s): Piaggio G, Heng Z, von Hertzen H, Bilian X, Linan C. Source: Contraception. 2003 December; 68(6): 439-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698074

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Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol. Author(s): Wiebe E, Dunn S, Guilbert E, Jacot F, Lugtig L. Source: Obstetrics and Gynecology. 2002 May; 99(5 Pt 1): 813-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978292

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Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. Author(s): Webb AM, Russell J, Elstein M. Source: Bmj (Clinical Research Ed.). 1992 October 17; 305(6859): 927-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1458074

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Contraception with mifepristone. Author(s): Swahn ML, Gemzell K, Bygdeman M. Source: Lancet. 1991 October 12; 338(8772): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1681282

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Contraception--a look forward, Part II: Mifepristone and gossypol. Author(s): Woolley RJ. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1991 March-April; 4(2): 103-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1823560

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Mifepristone

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Contraceptive efficacy of daily administration of 0.5 mg mifepristone. Author(s): Marions L, Viski S, Danielsson KG, Resch BA, Swahn ML, Bygdeman M, Kovacs L. Source: Human Reproduction (Oxford, England). 1999 November; 14(11): 2788-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10548623

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Contraceptive efficacy of low doses of mifepristone. Author(s): Marions L, Danielsson KG, Swahn ML, Bygdeman M. Source: Fertility and Sterility. 1998 November; 70(5): 813-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9806558

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Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women. Author(s): Croxatto HB, Salvatierra AM, Fuentealba B, Massai R. Source: Human Reproduction (Oxford, England). 1998 December; 13(12): 3297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886502

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Contragestion with late luteal administration of RU 486 (Mifepristone). Author(s): Dubois C, Ulmann A, Baulieu EE. Source: Fertility and Sterility. 1988 October; 50(4): 593-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3049166

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Corticotrophin-releasing factor immunostaining is present in placenta and fetal membranes from the first trimester onwards and is not affected by labour or administration of mifepristone. Author(s): Cooper ES, Brooks AN, Miller MR, Greer IA. Source: Clinical Endocrinology. 1994 November; 41(5): 677-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7828359

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Could American women use mifepristone-misoprostol pills safely with less medical supervision? Author(s): Harper C, Ellertson C, Winikoff B. Source: Contraception. 2002 February; 65(2): 133-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927116

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Curettage after mifepristone-induced abortion: frequency, timing, and indications. Author(s): Child TJ, Rees M, MacKenzie IZ. Source: Obstetrics and Gynecology. 2001 December; 98(6): 1149-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755574

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Curettage after mifepristone-induced abortion: frequency, timing, and indications. Author(s): Allen RH, Westhoff C, De Nonno L, Fielding SL, Schaff EA. Source: Obstetrics and Gynecology. 2001 July; 98(1): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430965

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Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days. Author(s): Brown A, Cheng L, Lin S, Baird DT. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 January; 87(1): 6370. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788624

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Determination of RU486 (mifepristone) in blood by radioreceptorassay; a pharmacokinetic study. Author(s): Foldesi I, Falkay G, Kovacs L. Source: Contraception. 1996 July; 54(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8804805

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Development after exposure to mifepristone in early pregnancy. Author(s): Pons JC, Imbert MC, Elefant E, Roux C, Herschkorn P, Papiernik E. Source: Lancet. 1991 September 21; 338(8769): 763. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1679900

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Development after in-utero exposure to mifepristone. Author(s): Ulmann A, Rubin I, Barnard J. Source: Lancet. 1991 November 16; 338(8777): 1270. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682662

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Dose and time dependent rise of plasma cortisol following administration of mifepristone in early pregnancy. Author(s): Thong KJ, Brooks AN, Baird DT. Source: British Journal of Obstetrics and Gynaecology. 1993 September; 100(9): 880-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8218022

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Double-blind randomized trial of mifepristone in combination with vaginal gemeprost or misoprostol for induction of abortion up to 63 days gestation. Author(s): Bartley J, Brown A, Elton R, Baird DT. Source: Human Reproduction (Oxford, England). 2001 October; 16(10): 2098-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574498

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Early abortion by mifepristone (RU 486) followed by vaginal gel (meteneprost) versus oral (misoprostol) prostaglandin. Author(s): Takkar D, Agarwal N, Sehgal R, Buckshee K. Source: Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception. 1999; 15(2): 163-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997897

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Early abortion induction by a combination of mifepristone and oral misoprostol. Author(s): Sanchez-Ramos L. Source: British Journal of Obstetrics and Gynaecology. 1995 June; 102(6): 506-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7632651

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Early pregnancy termination with intravaginally administered sodium chloride solution-moistened misoprostol tablets: historical comparison with mifepristone and oral misoprostol. Author(s): Jain JK, Meckstroth KR, Mishell DR Jr. Source: American Journal of Obstetrics and Gynecology. 1999 December; 181(6): 1386-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10601917

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Early pregnancy termination with mifepristone and misoprostol in the United States. Author(s): Spitz IM, Bardin CW, Benton L, Robbins A. Source: The New England Journal of Medicine. 1998 April 30; 338(18): 1241-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9562577

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Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth. Author(s): Cameron ST, Thong KJ, Baird DT. Source: Clinical Endocrinology. 1995 October; 43(4): 407-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7586613

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Effect of emergency contraception with levonorgestrel or mifepristone on ovarian function. Author(s): Marions L, Cekan SZ, Bygdeman M, Gemzell-Danielsson K. Source: Contraception. 2004 May; 69(5): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105059

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Effect of long-term treatment with low-dose mifepristone on the endometrium. Author(s): Baird DT, Brown A, Critchley HO, Williams AR, Lin S, Cheng L. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525442

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Effect of low daily doses of mifepristone on ovarian function and endometrial development. Author(s): Danielsson KG, Swahn ML, Westlund P, Johannisson E, Seppala M, Bygdeman M. Source: Human Reproduction (Oxford, England). 1997 January; 12(1): 124-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043916

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Effect of low weekly doses of mifepristone on ovarian function and endometrial development. Author(s): Gemzell-Danielsson K, Westlund P, Johannisson E, Swahn ML, Bygdeman M, Seppala M. Source: Human Reproduction (Oxford, England). 1996 February; 11(2): 256-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8671205

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Effect of mifepristone (RU486) on the pituitary response to gonadotrophin releasing hormone in women. Author(s): Kazem R, Messinis LE, Fowler P, Groome NP, Knight PG, Templeton AA. Source: Human Reproduction (Oxford, England). 1996 December; 11(12): 2585-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9021355

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Effect of mifepristone and levonorgestrel on expression of steroid receptors in the human Fallopian tube. Author(s): Christow A, Sun X, Gemzell-Danielsson K. Source: Molecular Human Reproduction. 2002 April; 8(4): 333-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11912281

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Effect of mifepristone approval on research remains to be seen. Author(s): Vastag B. Source: Journal of the National Cancer Institute. 2000 December 20; 92(24): 1970-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121453

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Effect of mifepristone on estrogen and progesterone receptors in human endometrial and endometriotic cells in vitro. Author(s): Jiang J, Wu RF, Wang ZH, Sun HC, Xu Z, Xiu HM. Source: Fertility and Sterility. 2002 May; 77(5): 995-1000. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009357

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Effect of mifepristone on folliculogenesis in women treated with recombinant FSH. Author(s): Messinis IE, Krishnan M, Kazem R, Khadilkar S, Templeton AA. Source: Clinical Endocrinology. 1997 March; 46(3): 309-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9156040

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Effect of once weekly administration of mifepristone on ovarian function in normal women. Author(s): Chen X, Xiao B. Source: Contraception. 1997 September; 56(3): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9347209

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Effect of two antiprogestins (mifepristone and onapristone) on endometrial factors of potential importance for implantation. Author(s): Cameron ST, Critchley HO, Buckley CH, Kelly RW, Baird DT. Source: Fertility and Sterility. 1997 June; 67(6): 1046-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9176442

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Effects of a sequential regimen of mifepristone-medroxyprogesterone acetate on ovarian function, endometrial development and hormonal parameters. Author(s): Croxatto HB, Massai MR, Salvatierra AM, Fuentealba B, Croxatto HD, Lahteenmaki P. Source: Contraception. 1996 August; 54(2): 79-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8842583

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Effects of daily low dose mifepristone on endometrial maturation and proliferation. Author(s): Cameron ST, Critchley HO, Thong KJ, Buckley CH, Williams AR, Baird DT. Source: Human Reproduction (Oxford, England). 1996 November; 11(11): 2518-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8981147

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Effects of gemeprost and mifepristone on the mechanical properties of the cervix prior to first trimester termination of pregnancy. Author(s): Carbonne B, Brennand JE, Maria B, Cabrol D, Calder AA. Source: British Journal of Obstetrics and Gynaecology. 1995 July; 102(7): 553-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7647058

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Effects of long-term low-dose mifepristone on reproductive function in women. Author(s): Croxatto HB, Kovacs L, Massai R, Resch BA, Fuentealba B, Salvatierra AM, Croxatto HD, Zalanyi S, Viski S, Krenacs L. Source: Human Reproduction (Oxford, England). 1998 April; 13(4): 793-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619526

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Effects of mifepristone on endometrial receptivity. Author(s): Danielsson KG, Marions L, Bygdeman M. Source: Steroids. 2003 November; 68(10-13): 1069-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668000

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Effects of mifepristone on expression of endothelial nitric oxide synthase in human endometrium during the implantation phase. Author(s): Sun X, Qiu X, Gemzell-Danielsson K. Source: Fertility and Sterility. 2003 December; 80(6): 1454-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667883

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Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo. Author(s): Li DQ, Wang ZB, Bai J, Zhao J, Wang Y, Hu K, Du YH. Source: World Journal of Gastroenterology : Wjg. 2004 June 15; 10(12): 1726-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188494

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Embryonic abnormalities at medical termination of pregnancy with mifepristone and misoprostol during first trimester: observational study. Author(s): Blanch G, Quenby S, Ballantyne ES, Gosden CM, Neilson JP, Holland K. Source: Bmj (Clinical Research Ed.). 1998 June 6; 316(7146): 1712-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614021

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Emergency contraception by low-dose mifepristone: observation of 150 cases. Author(s): Li FF, Chen YX, Tang JH. Source: Di Yi June Yi Da Xue Xue Bao. 2002 May; 22(5): 466-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390720

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Emergency contraception with mifepristone and levonorgestrel: mechanism of action. Author(s): Marions L, Hultenby K, Lindell I, Sun X, Stabi B, Gemzell Danielsson K. Source: Obstetrics and Gynecology. 2002 July; 100(1): 65-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100805

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Enhanced sensitivity of ovarian cell line to cisplatin induced by mifepristone and its mechanism. Author(s): Qin TN, Wang LL. Source: Di Yi June Yi Da Xue Xue Bao. 2002 April; 22(4): 344-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390742

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Enhancement of antitumor effect of cisplatin against human ovarian carcinoma cells by mifepristone in vivo. Author(s): Liu Y, Wang LL, Deng Y. Source: Di Yi June Yi Da Xue Xue Bao. 2003 March; 23(3): 242-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651241

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Expanded clinical trial of emergency contraception with 10 mg mifepristone. Author(s): Xiao B, Zhao H, Piaggio G, von Hertzen H. Source: Contraception. 2003 December; 68(6): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698073

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Experience and acceptability of medical abortion with mifepristone and misoprostol among U.S. women. Author(s): Beckman LJ, Harvey SM. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1997 July-August; 7(4): 253-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9283280

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Failure of oestrogen induced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days. Author(s): Baird DT, Thong KJ, Hall C, Cameron ST. Source: Human Reproduction (Oxford, England). 1995 September; 10(9): 2270-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8530650

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Feasibility of administering mifepristone as a once a month contraceptive pill. Author(s): Hapangama DK, Brown A, Glasier AF, Baird DT. Source: Human Reproduction (Oxford, England). 2001 June; 16(6): 1145-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11387284

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First trimester abortion with mifepristone and vaginal misoprostol. Author(s): Knudsen UB. Source: Contraception. 2001 May; 63(5): 247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448463

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Follicle stimulating hormone-granulosa cell axis involvement in the antifolliculotrophic effect of low dose mifepristone (RU486). Author(s): Croxatto HB, Salvatierra AM, Fuentealba B, Leiva L. Source: Human Reproduction (Oxford, England). 1995 August; 10(8): 1987-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8567827

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German drug agency approves mifepristone. Author(s): Tuffs A. Source: Bmj (Clinical Research Ed.). 1999 July 17; 319(7203): 141. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10406735

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Growth inhibition of androgen-insensitive human prostate carcinoma cells by a 19norsteroid derivative agent, mifepristone. Author(s): Lin MF, Kawachi MH, Stallcup MR, Grunberg SM, Lin FF. Source: The Prostate. 1995 April; 26(4): 194-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7716084

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Having an abortion using mifepristone and home misoprostol: a qualitative analysis of women's experiences. Author(s): Fielding SL, Edmunds E, Schaff EA. Source: Perspectives on Sexual and Reproductive Health. 2002 January-February; 34(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990637

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Hepatic metabolism and distribution of mifepristone and its metabolites in rats. Author(s): Heikinheimo O, Pesonen U, Huupponen R, Koulu M, Lahteenmaki P. Source: Human Reproduction (Oxford, England). 1994 June; 9 Suppl 1: 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7962468

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Hormone analytical and carrier protein alternations following administration of mifepristone (RU 486) for termination of early pregnancy. Author(s): Klinger G, Carol W, Borner A, Michels W, Romero KR. Source: Exp Clin Endocrinol. 1991 March; 97(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1864315

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Identification of CYP3A4 as the principal enzyme catalyzing mifepristone (RU 486) oxidation in human liver microsomes. Author(s): Jang GR, Wrighton SA, Benet LZ. Source: Biochemical Pharmacology. 1996 September 13; 52(5): 753-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8765473

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In vitro metabolism of mifepristone (RU-486) in rat, monkey and human hepatic S9 fractions: identification of three new mifepristone metabolites. Author(s): Wu WN, McKown LA, Moyer MD, Johannsen TB, Takacs AR. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1999 November; 29(11): 1089-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598744

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Induced cervical ripening with mifepristone (RU 486) and bioconversion of arachidonic acid in human pregnant uterine cervix in the first trimester. A doubleblind, randomized, biomechanical and biochemical study. Author(s): Radestad A, Bygdeman M, Green K. Source: Contraception. 1990 March; 41(3): 283-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2182288

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Induced cervical ripening with Mifepristone in first trimester abortion. A doubleblind randomized biomechanical study. Author(s): Radestad A, Christensen NJ, Stromberg L. Source: Contraception. 1988 September; 38(3): 301-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3168450

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Induction of abortion in early pregnancy with mifepristone in conjunction with gemeprost. Author(s): Somell C, Olund A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1993 January; 72(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8382430

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Induction of abortion in early pregnancy with mifepristone. Author(s): Somell C, Olund A. Source: Gynecologic and Obstetric Investigation. 1990; 29(1): 13-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2351330

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Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. Author(s): el-Refaey H, Templeton A. Source: Human Reproduction (Oxford, England). 1995 February; 10(2): 475-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7769082

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Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. Author(s): el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Source: The New England Journal of Medicine. 1995 April 13; 332(15): 983-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7885426

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Induction of abortion with mifepristone and misoprostol in early pregnancy. Author(s): Thong KJ, Baird DT. Source: British Journal of Obstetrics and Gynaecology. 1992 December; 99(12): 1004-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1477003

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Induction of antiproliferation and apoptosis in estrogen receptor negative MDA-231 human breast cancer cells by mifepristone and 4-hydroxytamoxifen combination therapy: a role for TGFbeta1. Author(s): Liang Y, Hou M, Kallab AM, Barrett JT, El Etreby F, Schoenlein PV. Source: International Journal of Oncology. 2003 August; 23(2): 369-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851686

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Induction of apoptosis by mifepristone and tamoxifen in human LNCaP prostate cancer cells in culture. Author(s): El Etreby MF, Liang Y, Lewis RW. Source: The Prostate. 2000 April 1; 43(1): 31-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725863

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Induction of early abortion with mifepristone (RU486) and two different doses of prostaglandin pessary (gemeprost). Author(s): Rodger MW, Logan AF, Baird DT. Source: Contraception. 1989 May; 39(5): 497-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2656087

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Induction of labor with mifepristone (RU 486) in intrauterine fetal death. Author(s): Cabrol D, Dubois C, Cronje H, Gonnet JM, Guillot M, Maria B, Moodley J, Oury JF, Thoulon JM, Treisser A, et al. Source: American Journal of Obstetrics and Gynecology. 1990 August; 163(2): 540-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2201190

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Induction of labor with mifepristone--a randomized, double-blind study versus placebo. Author(s): Stenlund PM, Ekman G, Aedo AR, Bygdeman M. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 October; 78(9): 793-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10535343

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Induction of labour with mifepristone after intrauterine fetal death. Author(s): Cabrol D, Bouvier D'Yvoire M, Mermet E, Cedard L, Sureau C, Baulieu EE. Source: Lancet. 1985 November 2; 2(8462): 1019. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2865498

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Induction of second trimester abortion with mifepristone and gemeprost. Author(s): Thong KJ, Baird DT. Source: British Journal of Obstetrics and Gynaecology. 1993 August; 100(8): 758-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8399016

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Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. Author(s): Rodger MW, Baird DT. Source: Lancet. 1987 December 19; 2(8573): 1415-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2891991

52

Mifepristone

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Inhibition of endometrial cancer cell lines by mifepristone (RU 486). Author(s): Schneider CC, Gibb RK, Taylor DD, Wan T, Gercel-Taylor C. Source: Journal of the Society for Gynecologic Investigation. 1998 November-December; 5(6): 334-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9824816

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Inhibition of ovulation by low-dose mifepristone (RU 486). Author(s): Ledger WL, Sweeting VM, Hillier H, Baird DT. Source: Human Reproduction (Oxford, England). 1992 August; 7(7): 945-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1331167

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Inhibition of P-glycoprotein activity in human leukemic cells by mifepristone. Author(s): Fardel O, Courtois A, Drenou B, Lamy T, Lecureur V, le Prise PY, Fauchet R. Source: Anti-Cancer Drugs. 1996 August; 7(6): 671-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8913436

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Interception. III: Postcoital luteal contragestion by an antiprogestin (mifepristone, RU 486) in 62 women. Author(s): van Santen MR, Haspels AA. Source: Contraception. 1987 May; 35(5): 423-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3040334

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Interception. IV: Failure of mifepristone (RU 486) as a monthly contragestive, "Lunarette". Author(s): van Santen MR, Haspels AA. Source: Contraception. 1987 May; 35(5): 433-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3040335

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Interruption of early pregnancy with mifepristone in combination with gemeprost. Author(s): Sandstrom O, Brooks L, Schantz A, Grinsted J, Grinsted L, Jacobsen JD, Nielsen SP. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 October; 78(9): 806-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10535346

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Is medical abortion acceptable to all American women: the impact of sociodemographic characteristics on the acceptability of mifepristone-misoprostol abortion. Author(s): Clark S, Ellertson C, Winikoff B. Source: J Am Med Womens Assoc. 2000; 55(3 Suppl): 177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10846333

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It is likely that CNM's prescriptive privileges will, in the near future, cover mifepristone and misoprostol. Author(s): Summers L. Source: Journal of Nurse-Midwifery. 1997 September-October; 42(5): 436-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9358712

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Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study. Author(s): Frydman R, Lelaidier C, Baton-Saint-Mleux C, Fernandez H, Vial M, Bourget P. Source: Obstetrics and Gynecology. 1992 December; 80(6): 972-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1448266

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Large endometrial polyp in a patient on long-term mifepristone therapy. Author(s): Martineau PA, Levental M. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2000 July; 19(7): 487-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898303

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Levonorgestrel and mifepristone in emergency contraception. Author(s): von Hertzen H, Piaggio G. Source: Steroids. 2003 November; 68(10-13): 1107-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668005

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Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia. Author(s): Newfield RS, Spitz IM, Isacson C, New MI. Source: Clinical Endocrinology. 2001 March; 54(3): 399-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298094

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Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Author(s): von Hertzen H, Piaggio G, Ding J, Chen J, Song S, Bartfai G, Ng E, GemzellDanielsson K, Oyunbileg A, Wu S, Cheng W, Ludicke F, Pretnar-Darovec A, Kirkman R, Mittal S, Khomassuridze A, Apter D, Peregoudov A; WHO Research Group on Postovulatory Methods of Fertility Regulation. Source: Lancet. 2002 December 7; 360(9348): 1803-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480356

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Low-dose mifepristone 200 mg and vaginal misoprostol for abortion. Author(s): Schaff EA, Eisinger SH, Stadalius LS, Franks P, Gore BZ, Poppema S. Source: Contraception. 1999 January; 59(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10342079

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Mifepristone

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Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Author(s): Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Source: Contraception. 2000 January; 61(1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10745068

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Low-dose mifepristone for uterine leiomyomata. Author(s): Eisinger SH, Meldrum S, Fiscella K, le Roux HD, Guzick DS. Source: Obstetrics and Gynecology. 2003 February; 101(2): 243-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576246

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Low-dose mifepristone inhibits endometrial proliferation and up-regulates androgen receptor. Author(s): Narvekar N, Cameron S, Critchley HO, Lin S, Cheng L, Baird DT. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 May; 89(5): 2491-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15126582

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Luteal phase treatment with mifepristone and misoprostol for fertility regulation. Author(s): Xiao B, von Hertzen H, Zhao H, Piaggio G. Source: Contraception. 2003 December; 68(6): 477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698078

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Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486). Author(s): He K, Woolf TF, Hollenberg PF. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 February; 288(2): 791-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9918590

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Mechanism-based inhibition of rat liver microsomal diazepam C3-hydroxylase by mifepristone associated with loss of spectrally detectable cytochrome P450. Author(s): Reilly PE, Gomi RJ, Mason SR. Source: Chemico-Biological Interactions. 1999 March 1; 118(1): 39-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227577

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Mechanisms of action of mifepristone when used for emergency contraception. Author(s): Gemzell-Danielsson K, Mandl I, Marions L. Source: Contraception. 2003 December; 68(6): 471-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698077

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Medical abortion alternatives to mifepristone. Author(s): Creinin MD, Pymar HC. Source: J Am Med Womens Assoc. 2000; 55(3 Suppl): 127-32, 150. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10846321

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Medical abortion at 57 to 63 days' gestation with a lower dose of mifepristone and gemeprost. A randomized controlled trial. Author(s): World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 May; 80(5): 447-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328223

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Medical abortion with mifepristone: an update. Author(s): Vason ES. Source: Jaapa. 2003 March; 16(3): 49-52, 54. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968525

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Medical treatment of ectopic pregnancies: a randomized clinical trial comparing methotrexate-mifepristone and methotrexate-placebo. Author(s): Rozenberg P, Chevret S, Camus E, de Tayrac R, Garbin O, de Poncheville L, Coiffic J, Lucot JP, Le Goueff F, Tardif D, Allouche C, Fernandez H; GROG. Source: Human Reproduction (Oxford, England). 2003 September; 18(9): 1802-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923131

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Menstrual induction with mifepristone and misoprostol. Author(s): Xiao B, von Hertzen H, Zhao H, Piaggio G. Source: Contraception. 2003 December; 68(6): 489-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698080

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Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Author(s): Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L. Source: Contraception. 2003 December; 68(6): 447-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698075

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Mifepristone abortion outside the urban research hospital setting in India. Author(s): Coyaji K, Elul B, Krishna U, Otiv S, Ambardekar S, Bopardikar A, Raote V, Ellertson C, Winikoff B. Source: Lancet. 2001 January 13; 357(9250): 120-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11197403

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Mifepristone

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Mifepristone and methotrexate: the combination for medical treatment of ectopic pregnancy. Author(s): Gazvani MR, Emery SJ. Source: American Journal of Obstetrics and Gynecology. 1999 June; 180(6 Pt 1): 1599-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10368554

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Mifepristone and misoprostol and methotrexate/misoprostol in clinical practice for abortion. Author(s): Creinin MD, Potter C, Holovanisin M, Janczukiewicz L, Pymar HC, Schwartz JL, Meyn L. Source: American Journal of Obstetrics and Gynecology. 2003 March; 188(3): 664-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634638

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Mifepristone and misoprostol for early medical abortion: 18 months experience in the United States. Author(s): Hausknecht R. Source: Contraception. 2003 June; 67(6): 463-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814815

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Mifepristone and misoprostol for medical termination of pregnancy: the effectiveness of a flexible regimen. Author(s): Basu R, Gundlach T, Tasker M. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2003 July; 29(3): 139-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885307

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Mifepristone and misoprostol versus dilation and evacuation for midtrimester abortion: a pilot randomised controlled trial. Author(s): Grimes DA, Smith MS, Witham AD. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2004 February; 111(2): 148-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723752

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Mifepristone as a late post-coital contraceptive. Author(s): Ashok PW, Wagaarachchi PT, Flett GM, Templeton A. Source: Human Reproduction (Oxford, England). 2001 January; 16(1): 72-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139540

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Mifepristone for induction of labour. Author(s): Neilson JP. Source: Cochrane Database Syst Rev. 2000; (4): Cd002865. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11034779

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Mifepristone for luteal phase contraception. Author(s): Croxatto HB. Source: Contraception. 2003 December; 68(6): 483-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698079

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Mifepristone for medical abortion. Exploring a new option for nurse practitioners. Author(s): Taylor D, Hwang AC. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2003 December-2004 January; 7(6): 524-9. Review. Erratum In: Awhonn Lifelines. 2004 April-May; 8(2): 101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753095

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Mifepristone for preinduction cervical ripening beyond 41 weeks' gestation: a randomized controlled trial. Author(s): Wing DA, Fassett MJ, Mishell DR. Source: Obstetrics and Gynecology. 2000 October; 96(4): 543-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11004356

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Mifepristone for the prevention of breakthrough bleeding in new starters of depomedroxyprogesterone acetate. Author(s): Jain JK, Nicosia AF, Nucatola DL, Lu JJ, Kuo J, Felix JC. Source: Steroids. 2003 November; 68(10-13): 1115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668006

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Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study. Author(s): Ashok PW, Flett GM, Templeton A. Source: American Journal of Obstetrics and Gynecology. 2000 October; 183(4): 998-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035353

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Mifepristone. Author(s): Executive Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). Source: J Obstet Gynaecol Can. 2003 March; 25(3): 235, 236. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610677

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Mifepristone: a novel estrogen-free daily contraceptive pill. Author(s): Baird DT, Brown A, Cheng L, Critchley HO, Lin S, Narvekar N, Williams AR. Source: Steroids. 2003 November; 68(10-13): 1099-105. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668004

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Mifepristone: less obvious adverse effects. Author(s): Rudd G. Source: The Annals of Pharmacotherapy. 2001 March; 35(3): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261540

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Mifepristone--a boom or a bust? Author(s): Willke JC. Source: The Annals of Pharmacotherapy. 2001 March; 35(3): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261539

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Mifepristone--controversy, beliefs, and politics--issues for everyone. Author(s): Hussar DA. Source: The Annals of Pharmacotherapy. 2001 March; 35(3): 373-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261538

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Mifepristone-induced abortion and birth weight in the first subsequent pregnancy. Author(s): Yimin C, Wei Y, Weidong C, Xianmi W, Junqing W, Lin L. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2004 March; 84(3): 229-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001370

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Mifepristone-induced early abortion and outcome of subsequent wanted pregnancy. Author(s): Chen A, Yuan W, Meirik O, Wang X, Wu SZ, Zhou L, Luo L, Gao E, Cheng Y. Source: American Journal of Epidemiology. 2004 July 15; 160(2): 110-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15234931

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Mifepristone-misoprostol medical abortion: home administration of misoprostol in Guadeloupe. Author(s): Guengant JP, Bangou J, Elul B, Ellertson C. Source: Contraception. 1999 September; 60(3): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10640161

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New applications of mifepristone (RU 486). Foreword. Author(s): London S. Source: Clinical Obstetrics and Gynecology. 1996 June; 39(2): 423. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8734006

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Normal development after exposure to mifepristone in early pregnancy. Author(s): Lim BH, Lees DA, Bjornsson S, Lunan CB, Cohn MR, Stewart P, Davey A. Source: Lancet. 1990 July 28; 336(8709): 257-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1973813

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Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel. Author(s): Cheng L, Zhu H, Wang A, Ren F, Chen J, Glasier A. Source: Human Reproduction (Oxford, England). 2000 September; 15(9): 1969-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10966997

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Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol. Author(s): Swahn ML, Bygdeman M, Chen JK, Gemzell-Danielsson K, Song S, Yang QY, Yang PJ, Qian ML, Chang WF. Source: Human Reproduction (Oxford, England). 1999 February; 14(2): 485-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099999

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Oral misoprostol versus mifepristone for cervical dilatation before vacuum aspiration in first trimester nulliparous pregnancy: a double blind prospective randomised study. Author(s): Ngai SW, Yeung KC, Lao T, Ho PC. Source: British Journal of Obstetrics and Gynaecology. 1996 November; 103(11): 1120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8917000

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Outcomes of suction curettage and mifepristone abortion in the United States. A prospective comparison study. Author(s): Jensen JT, Astley SJ, Morgan E, Nichols MD. Source: Contraception. 1999 March; 59(3): 153-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10382077

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Outpatient therapeutic abortion with mifepristone. Author(s): Ylikorkala O, Alfthan H, Kaariainen M, Rapeli T, Lahteenmaki P. Source: Obstetrics and Gynecology. 1989 October; 74(4): 653-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2797643

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P29, an oestrogen receptor-associated protein, is down-regulated by mifepristone in first trimester human placenta and decidua. Author(s): Rivera J, Hill NC, Lopez Bernal A, Mackenzie IZ, Cano A. Source: Human Reproduction (Oxford, England). 1991 October; 6(9): 1338-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1752938

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p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex. Author(s): Ito K, Jazrawi E, Cosio B, Barnes PJ, Adcock IM. Source: The Journal of Biological Chemistry. 2001 August 10; 276(32): 30208-15. Epub 2001 June 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11395507

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Parity is a major determinant of success rate in medical abortion: a retrospective analysis of 3161 consecutive cases of early medical abortion treated with reduced doses of mifepristone and vaginal gemeprost. Author(s): Bartley J, Tong S, Everington D, Baird DT. Source: Contraception. 2000 December; 62(6): 297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239616

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Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone). Author(s): Fried G, Meister B, Radestad A. Source: Human Reproduction (Oxford, England). 1990 October; 5(7): 870-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1702449

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Persistent ascites after ovarian hyperstimulation syndrome and administration of mifepristone (RU 486) for the termination of pregnancy. Author(s): Gnoth C, Halbe E, Freundl G. Source: Archives of Gynecology and Obstetrics. 2003 April; 268(1): 65-8. Epub 2003 February 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673480

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Pharmacokinetics of 10 mg of mifepristone. Author(s): Leminen R, Ranta S, von Hertzen H, Oehler J, Heikinheimo O. Source: Contraception. 2003 December; 68(6): 427-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698072

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Pharmacokinetics of mifepristone after low oral doses. Author(s): Kekkonen R, Heikinheimo O, Mandelin E, Lahteenmaki P. Source: Contraception. 1996 October; 54(4): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8922876

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Pharmacological properties of mifepristone: toxicology and safety in animal and human studies. Author(s): Sitruk-Ware R, Spitz IM. Source: Contraception. 2003 December; 68(6): 409-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698070

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Phase II study of the progesterone antagonist mifepristone in patients with untreated metastatic breast carcinoma: a National Cancer Institute of Canada Clinical Trials Group study. Author(s): Perrault D, Eisenhauer EA, Pritchard KI, Panasci L, Norris B, Vandenberg T, Fisher B. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 October; 14(10): 2709-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8874331

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Pilot study on the use of a two-week course of oral misoprostol in patients after termination of pregnancy with mifepristone and misoprostol. Author(s): Tang OS, Gao PP, Cheng L, Lee S, Ho PC. Source: Contraception. 1998 February; 57(2): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9589834

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Pilot study on the use of sublingual misoprostol with mifepristone in termination of first trimester pregnancy up to 9 weeks gestation. Author(s): Tang OS, Xu J, Cheng L, Lee SW, Ho PC. Source: Human Reproduction (Oxford, England). 2002 July; 17(7): 1738-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093832

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Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey. Author(s): Lalitkumar PG, Sengupta J, Karande AA, Ghosh D. Source: Human Reproduction (Oxford, England). 1998 December; 13(12): 3478-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886536

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Postcoital contraception with mifepristone. Author(s): Glasier A, Thong KJ, Dewar M, Mackie M, Baird DT. Source: Lancet. 1991 June 8; 337(8754): 1414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1674786

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Predictors of analgesia use during supervised medical abortion. The Mifepristone Clinical Trials Group. Author(s): Westhoff C, Dasmahapatra R, Winikoff B, Clarke S. Source: Contraception. 2000 March; 61(3): 225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10827337

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Predictors of failed attempted abortion with the antiprogestin mifepristone (RU 486). Author(s): Grimes DA, Bernstein L, Lacarra M, Shoupe D, Mishell DR Jr. Source: American Journal of Obstetrics and Gynecology. 1990 April; 162(4): 910-5; Discussion 915-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2183618

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Pregnancy interruption using mifepristone (RU-486). A new choice for women in the USA. Author(s): Mackenzie SJ, Yeo S. Source: Journal of Nurse-Midwifery. 1997 March-April; 42(2): 86-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9107115

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Pregnancy interruption using mifepristone (RU-486): a new choice for women in the USA. Author(s): Narrigan D. Source: Journal of Nurse-Midwifery. 1998 March-April; 43(2): 122. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9581100

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Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU 486). Author(s): Kettel LM, Murphy AA, Morales AJ, Yen SS. Source: American Journal of Obstetrics and Gynecology. 1998 June; 178(6): 1151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9662295

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Preliminary results with the antiprogestational compound RU-486 (mifepristone) for interruption of early pregnancy. Author(s): Vervest HA, Haspels AA. Source: Fertility and Sterility. 1985 November; 44(5): 627-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2414136

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Pre-operative cervical preparation before first trimester vacuum aspiration: a randomized controlled comparison between gemeprost and mifepristone (RU 486). Author(s): Henshaw RC, Templeton AA. Source: British Journal of Obstetrics and Gynaecology. 1991 October; 98(10): 1025-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1751434

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Presenting health risks honestly: mifepristone, a case in point. Author(s): Stewart FH, Shields WC, Hwang AC. Source: Contraception. 2004 March; 69(3): 177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969663

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Pretreatment of the primigravid uterine cervix with mifepristone 30 h prior to termination of pregnancy: a double blind study. Author(s): Cohn M, Stewart P. Source: British Journal of Obstetrics and Gynaecology. 1991 August; 98(8): 778-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1911585

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Pretreatment with mifepristone (RU 486) reduces interval between prostaglandin administration and expulsion in second trimester abortion. Author(s): Rodger MW, Baird DT. Source: British Journal of Obstetrics and Gynaecology. 1990 January; 97(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2407284

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Procedures on handling mifepristone (RU 486) in France. Author(s): Sarrut B, Doreau C. Source: Hosp Pharm. 1990 July; 25(7): 655-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10105331

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Professional considerations for providing mifepristone-induced abortion. Author(s): Fielding SL, Lee SS, Schaff EA. Source: The Nurse Practitioner. 2001 November; 26(11): 44-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11759615

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Progesterone receptor isoform B in the human fallopian tube and endometrium following mifepristone. Author(s): Sun X, Christow A, Marions L, Gemzell-Danielsson K. Source: Contraception. 2003 April; 67(4): 319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684155

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Promegestone (R5020) and mifepristone (RU486) both function as progestational agonists of human glycodelin gene expression in isolated human epithelial cells. Author(s): Taylor RN, Savouret JF, Vaisse C, Vigne JL, Ryan I, Hornung D, Seppala M, Milgrom E. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 November; 83(11): 4006-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9814484

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Providing mifepristone-misoprostol medical abortion: the view from the clinic. Author(s): Ellertson C, Simonds W, Winikoff B, Springer K, Bagchi D. Source: J Am Med Womens Assoc. 1999 Spring; 54(2): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319598

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Psychological responses following medical abortion (using mifepristone and gemeprost) and surgical vacuum aspiration. A patient-centered, partially randomised prospective study. Author(s): Henshaw R, Naji S, Russell I, Templeton A. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1994 November; 73(10): 812-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7817735

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Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Author(s): Ngai SW, Tang OS, Ho PC. Source: Human Reproduction (Oxford, England). 2000 October; 15(10): 2205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006200

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Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion. Author(s): Baird DT, Sukcharoen N, Thong KJ. Source: Human Reproduction (Oxford, England). 1995 June; 10(6): 1521-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7593528

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Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy. Author(s): Schaff EA, Fielding SL, Westhoff C. Source: Contraception. 2002 October; 66(4): 247-50. Erratum In: Contraception. 2002 December; 66(6): 481. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413620

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Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Author(s): Schaff EA, Fielding SL, Westhoff C. Source: Contraception. 2001 August; 64(2): 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704083

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Rapid reversal of acute psychosis in the Cushing syndrome with the cortisol-receptor antagonist mifepristone (RU 486). Author(s): van der Lely AJ, Foeken K, van der Mast RC, Lamberts SW. Source: Annals of Internal Medicine. 1991 January 15; 114(2): 143-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1984391

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Rapid reversal of psychotic depression using mifepristone. Author(s): Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF. Source: Journal of Clinical Psychopharmacology. 2001 October; 21(5): 516-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593077

Studies

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Reducing the induction to abortion interval in termination of second trimester pregnancies: a comparison of mifepristone with laminaria tent. Author(s): Ho PC, Tsang SS, Ma HK. Source: British Journal of Obstetrics and Gynaecology. 1995 August; 102(8): 648-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7654644

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Regulating gene expression using self-inactivating lentiviral vectors containing the mifepristone-inducible system. Author(s): Sirin O, Park F. Source: Gene. 2003 December 24; 323: 67-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659880

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Reproductive hormones during termination of early pregnancy with mifepristone. Author(s): Somell C, Olund A, Carlstrom K, Kindahl H. Source: Gynecologic and Obstetric Investigation. 1990; 30(4): 224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2289703

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Research on mifepristone and levonorgestrel in comparison with the Yuzpe regimen. Author(s): von Hertzen H. Source: J Am Med Womens Assoc. 1998; 53(5 Suppl 2): 222-4, 232. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9859626

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Response to the antiprogestagen RU 486 (mifepristone) during early pregnancy and the menstrual cycle in women. Author(s): Spitz IM, Shoupe D, Sitruk-Ware R, Mishell DR Jr. Source: J Reprod Fertil Suppl. 1989; 37: 253-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2681741

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Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone. Author(s): Li DQ, Wang ZB, Bai J, Zhao J, Wang Y, Hu K, Du YH. Source: World Journal of Gastroenterology : Wjg. 2004 June 15; 10(12): 1722-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188493

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RU 486 (mifepristone). Author(s): Grimes DA. Source: The Western Journal of Medicine. 1992 June; 156(6): 648. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1615658

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RU 486 (mifepristone). A short overview of its mechanisms of action and clinical uses at the end of 1996. Author(s): Baulieu EE. Source: Annals of the New York Academy of Sciences. 1997 September 26; 828: 47-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9329823

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RU 486 (mifepristone): clinical trials in China. Author(s): Zheng SR. Source: Acta Obstetricia Et Gynecologica Scandinavica. Supplement. 1989; 149: 19-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2694737

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RU 486 (mifepristone): induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys. Author(s): Neulen J, Williams RF, Hodgen GD. Source: The Journal of Clinical Endocrinology and Metabolism. 1990 October; 71(4): 1074-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2401709

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RU 486, mifepristone: a review of a controversial drug. Author(s): DiPierri D. Source: The Nurse Practitioner. 1994 June; 19(6): 59-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8065661

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RU486 (mifepristone): mechanisms of action and clinical uses. Author(s): Cadepond F, Ulmann A, Baulieu EE. Source: Annual Review of Medicine. 1997; 48: 129-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9046951

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Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: a comparative trial of mifepristone-misoprostol versus surgical abortion. Author(s): Winikoff B, Sivin I, Coyaji KJ, Cabezas E, Xiao B, Gu S, Du MK, Krishna UR, Eschen A, Ellertson C. Source: American Journal of Obstetrics and Gynecology. 1997 February; 176(2): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9065194

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Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases. Author(s): Tang OS, Thong KJ, Baird DT. Source: Contraception. 2001 July; 64(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535210

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Second trimester termination of pregnancy for fetal anomaly or death: comparing mifepristone/misoprostol to gemeprost. Author(s): le Roux PA, Pahal GS, Hoffman L, Nooh R, El-Refaey H, Rodeck CH. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 March; 95(1): 52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11267720

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Second trimester therapeutic abortion using mifepristone and oral misoprostol in a woman with two previous caesarean sections and a cone biopsy. Author(s): Oteri O, Hopkins R. Source: The Journal of Maternal-Fetal Medicine. 1999 November-December; 8(6): 300-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10582866

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Side effects of mifepristone-misoprostol abortion versus surgical abortion. Data from a trial in China, Cuba, and India. Author(s): Elul B, Ellertson C, Winikoff B, Coyaji K. Source: Contraception. 1999 February; 59(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10361625

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Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men. Author(s): Wiedemann K, Lauer CJ, Hirschmann M, Knaudt K, Holsboer F. Source: The American Journal of Physiology. 1998 January; 274(1 Pt 1): E139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9458759

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Slowing the progression of cognitive decline in Alzheimer's disease using mifepristone. Author(s): Belanoff JK, Jurik J, Schatzberg LD, DeBattista C, Schatzberg AF. Source: Journal of Molecular Neuroscience : Mn. 2002 August-October; 19(1-2): 201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12212781

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Social context and the experience of a sample of U.S. women taking RU-486 (mifepristone) for early abortion. Author(s): Fielding SL, Schaff EA. Source: Qualitative Health Research. 2004 May; 14(5): 612-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15107166

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Spain brings forward mifepristone approval. Author(s): Bosch X. Source: Lancet. 1998 October 17; 352(9136): 1293. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11656952

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Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486). Author(s): Chu JW, Matthias DF, Belanoff J, Schatzberg A, Hoffman AR, Feldman D. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 August; 86(8): 3568-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11502780

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Successful mifepristone treatment of recurrent, inoperable meningioma. Author(s): Haak HR, de Keizer RJ, Hagenouw-Taal JC, van Seters AP, Vielvoye GJ, van Dulken H. Source: Lancet. 1990 July 14; 336(8707): 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1975312

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Synergistic effects of danazol and mifepristone on the cytotoxicity of UCN-01 in hormone-responsive breast cancer cells. Author(s): Yokoyama Y, Shinohara A, Takahashi Y, Wan X, Takahashi S, Niwa K, Tamaya T. Source: Anticancer Res. 2000 September-October; 20(5A): 3131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11062733

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Synergistic effects on pregnancy-termination activity of DL111-IT in combination with mifepristone. Author(s): Yang B, Fang RY. Source: Zhongguo Yao Li Xue Bao. 1996 July; 17(4): 361-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812725

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Systematic review of mifepristone for the treatment of uterine leiomyomata. Author(s): Steinauer J, Pritts EA, Jackson R, Jacoby AF. Source: Obstetrics and Gynecology. 2004 June; 103(6): 1331-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15172874

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Termination of 2nd and 3rd trimester pregnancies with mifepristone and misoprostol. Author(s): Jannet D, Aflak N, Abankwa A, Carbonne B, Marpeau L, Milliez J. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1996 December 27; 70(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9119097

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Termination of a molar pregnancy using mifepristone and gemeprost. Author(s): Bates A, Pinto A, Evans J. Source: British Journal of Obstetrics and Gynaecology. 1994 July; 101(7): 637-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8043548

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Termination of early human pregnancy with either 50 mg or 200 mg single oral dose of mifepristone (RU486) in combination with either 0.5 mg or 1.0 mg vaginal gemeprost. Author(s): Prasad RN, Choolani M. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1996 February; 36(1): 20-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8775244

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Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05--a multicentre randomized clinical trial in China. Author(s): Sang GW, Weng LJ, Shao QX, Du MK, Wu XZ, Lu YL, Cheng LN. Source: Contraception. 1994 December; 50(6): 501-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7705093

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Termination of early pregnancy in the scarred uterus with mifepristone and misoprostol. Author(s): Xu J, Chen H, Ma T, Wu X. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 March; 72(3): 245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11226445

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Termination of early pregnancy with a reduced oral dose of mifepristone and vaginal misoprostol. Author(s): Anjum ZK. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2000 September; 90(9): 889-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081141

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Termination of pregnancy at 9-13 weeks' amenorrhoea with mifepristone and misoprostol. Author(s): Ashok PW, Flett GM, Templeton A. Source: Lancet. 1998 August 15; 352(9127): 542-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9716062

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Termination of pregnancy with mifepristone and prostaglandin suppresses transiently circulating glucocorticoid bioactivity. Author(s): Heikinheimo O, Raivio T, Honkanen H, Ranta S, Janne OA. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 January; 88(1): 3236. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519872

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Termination of second trimester pregnancy with mifepristone and gemeprost. The clinical experience of 197 consecutive cases. Author(s): Gemzell-Danielsson K, Ostlund E. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 August; 79(8): 702-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10949238

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Termination of second trimester pregnancy with sulprostone and mifepristone: a randomized double-blind placebo-controlled trial. Author(s): Ho PC, Ma HK. Source: Contraception. 1993 February; 47(2): 123-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8449013

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The approval of mifepristone (RU486) in the United States: What's wrong with this picture? Author(s): Blumenthal P, Johnson J, Stewart F. Source: Medscape Women's Health [electronic Resource]. 2000 July-August; 5(4): E7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109052

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The effect of a single dose of mifepristone (RU486) on the fine structure of the human endometrium during the early luteal phase. Author(s): Dockery P, Ismail RM, Li TC, Warren MA, Cooke ID. Source: Human Reproduction (Oxford, England). 1997 August; 12(8): 1778-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9308811

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The effect of mifepristone administration on leukocyte populations, matrix metalloproteinases and inflammatory mediators in the first trimester cervix. Author(s): Denison FC, Riley SC, Elliott CL, Kelly RW, Calder AA, Critchley HO. Source: Molecular Human Reproduction. 2000 June; 6(6): 541-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825372

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The effect of mifepristone on the expression of insulin-like growth factor binding protein-1, prolactin and progesterone receptor mRNA and protein during the implantation phase in human endometrium. Author(s): Qiu X, Sun X, Christow A, Stabi B, Gemzell-Danielsson K. Source: Molecular Human Reproduction. 2002 November; 8(11): 998-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397212

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The effect of mifepristone on the expression of steroid hormone receptors in human decidua and placenta: a randomized placebo-controlled double-blind study. Author(s): Chan CC, Lao TT, Ho PC, Sung EO, Cheung AN. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 December; 88(12): 5846-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671179

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The effect of various doses of mifepristone on endometrial leukaemia inhibitory factor expression in the midluteal phase--an immunohistochemical study. Author(s): Danielsson KG, Swahn ML, Bygdeman M. Source: Human Reproduction (Oxford, England). 1997 June; 12(6): 1293-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9222019

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The effects of the antiprogesterone RU486 (Mifepristone) on an endometrial secretory glycan: an immunocytochemical study. Author(s): Graham RA, Li TC, Seif MW, Aplin JD, Cooke ID. Source: Fertility and Sterility. 1991 June; 55(6): 1132-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1709886

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The endocrine effects of long-term treatment with mifepristone (RU 486). Author(s): Lamberts SW, Koper JW, de Jong FH. Source: The Journal of Clinical Endocrinology and Metabolism. 1991 July; 73(1): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1646217

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The mifepristone-misoprostol regimen for early medical abortion. Author(s): Ellertson C, Waldman SN. Source: Curr Womens Health Rep. 2001 December; 1(3): 184-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112968

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The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Author(s): Heikinheimo O, Kekkonen R, Lahteenmaki P. Source: Contraception. 2003 December; 68(6): 421-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698071

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The possibility of using mifepristone for menstrual induction. Author(s): Bygdeman M. Source: Contraception. 2003 December; 68(6): 495-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698081

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The potential of mifepristone (RU486) as a female contraceptive drug. Author(s): Sarkar NN. Source: Int J Clin Pract. 2002 March; 56(2): 140-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926701

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Time to relax the rules about administration of mifepristone. Author(s): Omokanye S. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2001 April; 27(2): 102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457525

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Timing of pain and bleeding after mifepristone-induced abortion. Author(s): De Nonno LJ, Westhoff C, Fielding S, Schaff E. Source: Contraception. 2000 December; 62(6): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239617

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Tissue and serum levels of steroid hormones and RU 486 after administration of mifepristone. Author(s): Wang JD, Shi WL, Zhang GQ, Bai XM. Source: Contraception. 1994 March; 49(3): 245-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8200218

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Toxic epidermal necrolysis after mifepristone/gemeprost-induced abortion. Author(s): Lecorvaisier-Pieto C, Joly P, Thomine E, Tanasescu S, Noblet C, Lauret P. Source: Journal of the American Academy of Dermatology. 1996 July; 35(1): 112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8682946

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Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy. Author(s): Hill NC, Selinger M, Ferguson J, MacKenzie IZ. Source: Human Reproduction (Oxford, England). 1991 March; 6(3): 458-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1955558

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Treatment of endometriosis with the antiprogesterone mifepristone (RU486) Author(s): Kettel LM, Murphy AA, Morales AJ, Ulmann A, Baulieu EE, Yen SS. Source: Fertility and Sterility. 1996 January; 65(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8557150

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Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. Author(s): Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russell CA, Lucci L, Stevenson LL. Source: Journal of Neurosurgery. 1991 June; 74(6): 861-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2033444

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Use of mifepristone as an example of conflicting and misleading medical information on the internet. Author(s): Mashiach R, Seidman GI, Seidman DS. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 April; 109(4): 437-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013165

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Use of various ultrasonographic criteria to evaluate the efficacy of mifepristone and misoprostol for medical abortion. Author(s): Creinin MD, Spitz IM. Source: American Journal of Obstetrics and Gynecology. 1999 December; 181(6): 1419-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10601923

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Uterine activity and decidual prostaglandin production in women in early pregnancy in response to mifepristone with or without indomethacin in vivo. Author(s): Norman JE, Kelly RW, Baird DT. Source: Human Reproduction (Oxford, England). 1991 May; 6(5): 740-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1939561

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Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone. Author(s): Norman JE, Thong KJ, Baird DT. Source: Lancet. 1991 November 16; 338(8777): 1233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682644

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Uterine rupture during second trimester termination of pregnancy using mifepristone and a prostaglandin. Author(s): Phillips K, Berry C, Mathers AM. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1996 April; 65(2): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8730620

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Uterine rupture during therapeutic abortion in the second trimester using mifepristone and prostaglandin. Author(s): Thong KJ, Lynch P, Baird DT. Source: British Journal of Obstetrics and Gynaecology. 1995 October; 102(10): 844-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547753

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Uterine rupture during therapeutic abortion in the second trimester using mifepristone and prostaglandin. Author(s): Norman JE. Source: British Journal of Obstetrics and Gynaecology. 1995 April; 102(4): 332-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7612519

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Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial. Author(s): Schaff EA, Fielding SL, Westhoff C, Ellertson C, Eisinger SH, Stadalius LS, Fuller L. Source: Jama : the Journal of the American Medical Association. 2000 October 18; 284(15): 1948-53. Erratum In: Jama 2000 November 22-29; 284(20): 2597. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035891

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Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. Author(s): Schaff EA, Stadalius LS, Eisinger SH, Franks P. Source: The Journal of Family Practice. 1997 April; 44(4): 353-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9108832

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Vascular endothelial growth factor mRNA and its protein expression in decidua after terminating early pregnancy by mifepristone plus misoprostol. Author(s): Huang L, Shi Y. Source: Chinese Medical Journal. 2001 May; 114(5): 517-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11780417

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Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience. Author(s): Silvestre L, Dubois C, Renault M, Rezvani Y, Baulieu EE, Ulmann A. Source: The New England Journal of Medicine. 1990 March 8; 322(10): 645-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2304490

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Warning on low dose mifepristone use. Author(s): Ulmann A. Source: Pharmacoeconomics. 1994 July; 6(1): 90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10147355

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WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. Author(s): Honkanen H, Piaggio G, Hertzen H, Bartfai G, Erdenetungalag R, GemzellDanielsson K, Gopalan S, Horga M, Jerve F, Mittal S, Thi Nhu Ngoc N, Peregoudov A, Prasad RN, Pretnar-Darovec A, Shah RS, Song S, Tang OS, Wu SC; WHO Research Group on Post-Ovulatory Methods for Fertility Regulation. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2004 July; 111(7): 715-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198763

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WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: Efficacy. Author(s): von Hertzen H, Honkanen H, Piaggio G, Bartfai G, Erdenetungalag R, Gemzell-Danielsson K, Gopalan S, Horga M, Jerve F, Mittal S, Ngoc NT, Peregoudov A, Prasad RN, Pretnar-Darovec A, Shah RS, Song S, Tang OS, Wu SC; WHO Research Group on Post-Ovulatory Methods for Fertility Regulation. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 September; 110(9): 808-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511962

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CHAPTER 2. NUTRITION AND MIFEPRISTONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and mifepristone.

Finding Nutrition Studies on Mifepristone 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 “mifepristone” (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 “mifepristone” (or a synonym): •

A slow start to the new millennium. Zyvox, Concerta and Mifeprex headline the year. Source: Cornell, S Adv-Nurse-Pract. 2000 December; 8(12): 62-4 1096-6293

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Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial. World Health Organisation Task Force on Postovulatory Methods of Fertility Regulation. Author(s): Special Programme of Research, Development and Research Training, World Health Organization, Geneva, Switzerland. Source: Anonymous BJOG. 2000 April; 107(4): 524-30

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Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. Author(s): Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pennsylvania 15213-3180, USA. Source: Creinin, M D Schwartz, J L PyMarch, H C Fink, W BJOG. 2001 May; 108(5): 46973 1470-0328

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In vivo antiestrogenic activity of mifepristone in the rat. Author(s): Institute of Endocrinology, Prague, Czech Republic. Source: Nedvidkova, J Schreiber, V Starka, L J-Endocrinol-Invest. 1997 April; 20(4): 225-9 0391-4097

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Lowering the doses of mifepristone and gameprost for early abortion: a randomised controlled trial. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation. Source: Anonymous BJOG. 2001 July; 108(7): 738-42 1470-0328

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Medical management of late intrauterine death using a combination of mifepristone and misoprostol. Author(s): Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, UK. Source: Wagaarachchi, Prabhath T Ashok, Premila W Narvekar, Nitish N Smith, Norman C Templeton, Allan BJOG. 2002 April; 109(4): 443-7 1470-0328

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Termination of early pregnancy using mifepristone in combination with prostaglandin analogs. Author(s): Department de Gynecologie-Obstetrique, Universite de Paris, Val de Marne, Centre Hospitalier, Villeneuve-Saint-Georges, France. Source: Maria, B Stampf, F Acta-Obstet-Gynecol-Scand-Suppl. 1989; 14931-2 0300-8835

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The effect of a single neonatal treatment (hormonal imprinting) with the antihormones, tamoxifen and mifepristone on the sexual behavior of adult rats. Author(s): Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1445 Budapest, P.O. Box 370, Hungary. [email protected] Source: Csaba, G Karabelyos, C Pharmacol-Res. 2001 June; 43(6): 531-4 1043-6618

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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/

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 MIFEPRISTONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to mifepristone. 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 mifepristone 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 “mifepristone” (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 mifepristone: •

A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Author(s): Ogg MS, Williams JM, Tarbit M, Goldfarb PS, Gray TJ, Gibson GG. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1999 March; 29(3): 269-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10219967

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A slow start to the new millennium. Zyvox, Concerta and Mifeprex headline the year. Author(s): Cornell S. Source: Adv Nurse Pract. 2000 December; 8(12): 62-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397912

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Alternative medical treatment for endometriosis. Author(s): Taylor H, Guarnaccia M, Olive D.

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Source: Semin Reprod Endocrinol. 1997; 15(3): 285-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9383837 •

Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. Author(s): Webster JI, Tonelli LH, Moayeri M, Simons SS Jr, Leppla SH, Sternberg EM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 May 13; 100(10): 5706-11. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724519

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Anti-inflammatory activity of two cucurbitacins isolated from Cayaponia tayuya roots. Author(s): Recio MC, Prieto M, Bonucelli M, Orsi C, Manez S, Giner RM, Cerda-Nicolas M, Rios JL. Source: Planta Medica. 2004 May; 70(5): 414-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15124085

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Complication of cesarean section: pregnancy on the cicatrix of a previous cesarean section. Author(s): Wang W, Long W, Yu Q. Source: Chinese Medical Journal. 2002 February; 115(2): 242-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940341

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Controlling mammalian gene expression with small molecules. Author(s): Clackson T. Source: Current Opinion in Chemical Biology. 1997 August; 1(2): 210-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9667854

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Corticosterone-induced rapid phosphorylation of p38 and JNK mitogen-activated protein kinases in PC12 cells. Author(s): Li X, Qiu J, Wang J, Zhong Y, Zhu J, Chen Y. Source: Febs Letters. 2001 March 16; 492(3): 210-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257496

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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy. Author(s): Courdier-Fruh I, Barman L, Wettstein P, Meier T. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 699-704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561491

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Dexamethasone induces resistance to the lethal consequences of electron transport inhibition in cultured hepatocytes. Author(s): Pastorino JG, Wilhelm TJ, Glascott PA Jr, Kocsis JJ, Farber JL.

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Source: Archives of Biochemistry and Biophysics. 1995 April 1; 318(1): 175-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7726559 •

Divergent regulation of the class II P-glycoprotein gene in primary cultures of hepatocytes versus H35 hepatoma by glucocorticoids. Author(s): Schuetz JD, Silverman JA, Thottassery JV, Furuya KN, Schuetz EG. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 1995 October; 6(10): 1321-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8845310

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Effect of early pregnancy on a previous lower segment cesarean section scar. Author(s): Weimin W, Wenqing L. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 June; 77(3): 201-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065130

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Effects of RU486 on the interstitial collagenase in the process of cervical ripening in the pregnant rat. Author(s): Ikuta Y, Matsuura K, Okamura H, Oyamada I, Usuku G. Source: Endocrinol Jpn. 1991 October; 38(5): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1843268

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Emergency contraception: a review. Author(s): Haspels AA. Source: Contraception. 1994 August; 50(2): 101-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7956209

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Evaluation of a Tier I screening battery for detecting endocrine-active compounds (EACs) using the positive controls testosterone, coumestrol, progesterone, and RU486. Author(s): O'Connor JC, Davis LG, Frame SR, Cook JC. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2000 April; 54(2): 338-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10774816

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Expression of xanthine oxidoreductase in mouse mammary epithelium during pregnancy and lactation: regulation of gene expression by glucocorticoids and prolactin. Author(s): Kurosaki M, Zanotta S, Li Calzi M, Garattini E, Terao M. Source: The Biochemical Journal. 1996 November 1; 319 ( Pt 3): 801-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8920983

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From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example. Author(s): Woodland C, Koren G, Ito S. Source: Journal of Clinical Pharmacology. 2003 July; 43(7): 743-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856388

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Ginsenoside-Rg1 regulates the induction of tyrosine aminotransferase gene transcription in rat hepatocyte cultures. Author(s): Kang SY, Lee KY, Lee SK. Source: Biochemical and Biophysical Research Communications. 1994 December 30; 205(3): 1696-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7811253

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Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Author(s): Lee YJ, Chung E, Lee KY, Lee YH, Huh B, Lee SK. Source: Molecular and Cellular Endocrinology. 1997 October 20; 133(2): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9406859

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Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs. Author(s): Flynn NE, Wu G. Source: The Journal of Nutrition. 1997 May; 127(5): 732-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9164994

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Heregulin induces transcriptional activation of the progesterone receptor by a mechanism that requires functional ErbB-2 and mitogen-activated protein kinase activation in breast cancer cells. Author(s): Labriola L, Salatino M, Proietti CJ, Pecci A, Coso OA, Kornblihtt AR, Charreau EH, Elizalde PV. Source: Molecular and Cellular Biology. 2003 February; 23(3): 1095-111. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529413

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Immortalized chromaffin cells disimmortalized with Cre/lox site-directed recombination for use in cell therapy for pain after partial nerve injury. Author(s): Eaton MJ, Herman JP, Jullien N, Lopez TL, Martinez M, Huang J. Source: Experimental Neurology. 2002 May; 175(1): 49-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009759

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In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells. Author(s): Lee YN, Lee HY, Chung HY, Kim SI, Lee SK, Park BC, Kim KW.

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Source: European Journal of Cancer (Oxford, England : 1990). 1996 July; 32A(8): 1420-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8869109 •

Induction of lipocortin 1 by topical steroid in rat skin. Author(s): Ahluwalia A, Mohamed RW, Flower RJ. Source: Biochemical Pharmacology. 1994 October 18; 48(8): 1647-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7980630

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Inductive effect of ginsenoside-Rg1 on tyrosine aminotransferase gene expression in rat primary hepatocyte cultures. Author(s): Kim MY, Lee KY, Lee SK. Source: Biochem Mol Biol Int. 1994 October; 34(4): 845-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7866312

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Inhibition of macrophage activation and lipopolysaccaride-induced death by secosteroids purified from Physalis angulata L. Author(s): Soares MB, Bellintani MC, Ribeiro IM, Tomassini TC, Ribeiro dos Santos R. Source: European Journal of Pharmacology. 2003 January 10; 459(1): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505539

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Inhibition of Vpr-induced cell cycle abnormality by quercetin: a novel strategy for searching compounds targeting Vpr. Author(s): Shimura M, Zhou Y, Asada Y, Yoshikawa T, Hatake K, Takaku F, Ishizaka Y. Source: Biochemical and Biophysical Research Communications. 1999 August 2; 261(2): 308-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425183

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Interaction of unsaturated fatty acids with rat liver glucocorticoid receptors: studies to localize the site of interaction. Author(s): Sumida C, Vallette G, Nunez EA. Source: Acta Endocrinol (Copenh). 1993 October; 129(4): 348-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8237254

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Intimidation and restraint of trade. Author(s): Martz EW. Source: Del Med J. 1990 October; 62(10): 1311. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2286288

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Legal trends in bioethics. Author(s): Davis DS.

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Source: J Clin Ethics. 1996 Fall; 7(3): 284-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11644881 •

Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Author(s): Whorwood CB, Sheppard MC, Stewart PM. Source: Endocrinology. 1993 June; 132(6): 2287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8504732

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Listening and learning from women about mifepristone: implications for counseling and health education. Author(s): Castle MA, Harvey SM, Beckman L, Coeytaux F, Garrity JM. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 1995 Fall; 5(3): 130-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7549491

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Methods for cervical ripening and induction of labor. Author(s): Tenore JL. Source: American Family Physician. 2003 May 15; 67(10): 2123-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776961

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Methods of cervical ripening and labor induction. Author(s): Summers L. Source: Journal of Nurse-Midwifery. 1997 March-April; 42(2): 71-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9107114

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Mineralocorticoid and glucocorticoid receptor antagonists in animal models of anxiety. Author(s): Korte SM, Korte-Bouws GA, Koob GF, De Kloet ER, Bohus B. Source: Pharmacology, Biochemistry, and Behavior. 1996 May; 54(1): 261-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8728567

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Modulation of androgen and progesterone receptors by phytochemicals in breast cancer cell lines. Author(s): Rosenberg RS, Grass L, Jenkins DJ, Kendall CW, Diamandis EP. Source: Biochemical and Biophysical Research Communications. 1998 July 30; 248(3): 935-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704030

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Other medical management of uterine fibroids. Author(s): Eldar-Geva T, Healy DL.

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Source: Baillieres Clin Obstet Gynaecol. 1998 June; 12(2): 269-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10023422 •

Pharmacists' beliefs about abortion and RU-486. Author(s): Giannetti V. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 1996 December; Ns36(12): 698-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9044802

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Pharmacological characterization of the ATP-dependent low K(m) guanosine 3',5'cyclic monophosphate (cGMP) transporter in human erythrocytes. Author(s): Sundkvist E, Jaeger R, Sager G. Source: Biochemical Pharmacology. 2002 March 1; 63(5): 945-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11911846

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Phase II study of mifepristone (RU486) in refractory ovarian cancer. Author(s): Rocereto TF, Saul HM, Aikins JA Jr, Paulson J. Source: Gynecologic Oncology. 2000 June; 77(3): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10831354

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Progesterone induces Ca++-dependent 3',5'-cyclic adenosine monophosphate increase in human sperm. Author(s): Parinaud J, Milhet P. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 April; 81(4): 135760. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8636333

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Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells. Author(s): Miyamoto H, Yeh S, Wilding G, Chang C. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 June 23; 95(13): 7379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636157

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Prostaglandin F2alpha-induced Ca++ oscillations in human myometrial cells and the role of RU 486. Author(s): Fu X, Favini R, Kindahl K, Ulmsten U. Source: American Journal of Obstetrics and Gynecology. 2000 March; 182(3): 582-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10739511

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Response of human ovarian carcinoma cell lines to antiprogestin mifepristone. Author(s): Rose FV, Barnea ER.

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Source: Oncogene. 1996 March 7; 12(5): 999-1003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8649817 •

The antiglucocorticoid action of mifepristone. Author(s): Agarwai MK. Source: Pharmacology & Therapeutics. 1996; 70(3): 183-213. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8888066

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 mifepristone; 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: •

Herbs and Supplements Mifepristone 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. PATENTS ON MIFEPRISTONE 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 “mifepristone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on mifepristone, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Mifepristone By performing a patent search focusing on mifepristone, 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. The following is an 8Adapted

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

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example of the type of information that you can expect to obtain from a patent search on mifepristone: •

Methods and compositions for inhibiting HIV replication Inventor(s): Levy; David N. (Birmingham, AL), Refaeli; Yosef (Boston, MA), Weiner; David B. (Merion, PA) Assignee(s): Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 5,780,220 Date filed: February 3, 1995 Abstract: A method for treating an individual exposed to or infected with HIV is disclosed which comprises administering to said individual a therapeutically effective amount of one or more compounds which inhibit or prevent replication of said HIV by interfering with the replicative or other essential functions of Vpr expressed by said HIV, by interactively blocking the Vpr target in human cells, and thereby preventing translocation of the Vpr/target complex from the cytosol of said human cells to the nuclei of said cells, where Vpr carries on activities essential to replication of HIV. In preferred embodiments, the compound or compounds which interactively block the target are steroid hormone receptor antagonists, glucocorticoid receptor antagonists, or glucocorticoid receptor Type II antagonists, especially mifepristone (RU-486). Pharmaceutical compositions comprising these compounds, as well as a method for identifying them and a kit for use therein, are also disclosed. Excerpt(s): The present invention is in the field of methods and compositions for treating human immunodeficiency virus (HIV) infected individuals by identifying such individuals and administering to such individuals, compositions which inhibit or prevent replication of the HIV. In particular, the present invention relates to compositions which inhibit or prevent the replicative and other essential functions of HIV viral protein R (Vpr) by interactively blocking the Vpr target in human cells. As described further below, the Vpr target may include, but is not necessarily limited to, the protein R interacting protein, hereinafter designated Rip-1. In accordance with the present invention, it has been discovered that the Vpr target in the human host cell involves Rip-1 alone or in association with, i.e., as a part of or functionally combined with, one or more steroid receptors in said host cell, especially the glucocorticoid receptor (GR), whereby a complex, comprising Vpr, Rip-1, said steroid receptor(s) and potentially other components, is formed which mediates the activities of Vpr essential to replication of HIV in said human host cell. The present invention also contemplates that the Vpr target may be one or more of said steroid receptors alone. Thus, the present invention is also in the putative field of inhibitory or antagonist compositions which by binding to, or otherwise wholly or partially precluding the functioning of Rip-1 alone or in association with a steroid receptor, especially a GR-type receptor, or potentially other components, or one or more steroid receptors alone, prevent Vpr from interacting with its target, especially comprising a multi-part complex which includes Rip-1, thereby preventing or interfering with the essential activities of Vpr necessary for HIV replication. In particular, in accordance with the present invention it is contemplated that the inhibitory or antagonist compositions disclosed herein prevent translocation of the Vpr/Rip-1 and/or steroid receptor or other component complex from the cytosol to the nucleus, or signaling of said translocated complex, whereby Vpr would otherwise carry on its various activities essential to replication of HIV. Thus, the present invention is also in the putative field of inhibitory or antagonist compositions which by binding to,

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or otherwise wholly or partially precluding the functioning of Rip-1 alone, or in association with a steroid receptor or other component, especially a GR-type receptor, or one or more steroid receptor alone, prevent or interfere with translocation of Vpr or the complex with which it is associated, from the cytosol to the nucleus of said human host cell, or the signaling of said translocated Vpr or complex, whereby the essential activities of said Vpr or complex necessary for HIV replication, are frustrated. Web site: http://www.delphion.com/details?pn=US05780220__ •

Use of low levels of mifepristone to treat leiomyomata Inventor(s): Yen; Samuel S. C. (La Jolla, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 5,468,741 Date filed: May 28, 1993 Abstract: This invention provides for novel unit doses of mifepristone to treat leiomyomata. Compared to unit dosages taught by the prior art, the claimed dosages are low and surprisingly effective. Furthermore, because higher dosages had undesired side effects, the prior art suggested that mifepristone was not suitable for long term clinical uses which are needed to treat leiomyomata. The advantages of this invention include a reduction of surgical morbidity, circumvent the need of a hysterectomy, and costeffectiveness. Excerpt(s): Leiomyomata are common pelvic fibroid tumors occurring in up to 20% of women over 30 years of age. Leiomyomata represent one of the most frequent indications of operative procedures in woman of reproductive age. Symptoms are reported in twenty to fifty percent of cases of leiomyomata. Symptoms include pelvic pain, excessive duration or amount of menstruation, infertility and pelvic masses. Although the mechanisms of tumorigenesis are unknown, evidence suggests that leiomyomata are ovarian steroid dependent, Buttram, V. C., et al. (1981), Fertil. Steril., 36:433, incorporated herein by reference. Estrogen and growth hormone are thought to act synergistically to stimulate leiomyomata growth as the two are elevated during pregnancy when the growth of leiomyomata is rapid. That progesterone may play a role in Leiomyomata growth is suggested by the finding of increased mitotic count in leiomyomata obtained during the secretory phase than in proliferative phase of the menstrual cycle; Kawaguchi, et al. (1988) Am. J. Obstet. Gynecol., 160:637. Additionally, when the GnRH-agonist and a progesterone were co-administered, the expected regression of leiomyomata size seen with GnRH-agonist alone is not achieved, Friedman et al (1988) Fertil. Steril. 49:404. Wilson, E. R., et al. (1980) Obstet. Gynecol., 55:22 and Soules, M. R., et al. (1982) Am. J. Obstet. Gynecol., 143:6 have identified receptors for both estrogen (ER) and progesterone (PR) leiomyomata tissue. Web site: http://www.delphion.com/details?pn=US05468741__

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Patent Applications on Mifepristone 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 mifepristone: •

Treatment and prevention of abnormal scar formation in keloids and other cutaneous or internal wounds or lesions Inventor(s): Benya, Paul D.; (Los Angeles, CA), Tuan, Tai-Lan; (Fullerton, CA), Warburton, David; (La Canada, CA) Correspondence: Perkins Coie Llp; Post Office Box 1208; Seattle; WA; 98111-1208; US Patent Application Number: 20040043026 Date filed: May 13, 2003 Abstract: The present invention relates to findings that reducing the activity of Plasminogen Activator Inhibitor-1 (PAI-1) suppresses an excessive deposition of collagen which is known as a cause for the formation of abnormal scars. These abnormal scars include but are not limited to keloids, adhesions, hypertrophic scars, skin disfiguring conditions, fibrosis, fibrocystic conditions, contractures, and scleroderma, all of which are associated with or caused by an excessive deposit of collagen in a wound healing process. Accordingly, aspects of the present invention are directed to the reduction of PAI-1 activity to decrease an excessive accumulation of collagen, prevent the formation of an abnormal scar, and/or treat abnormal scars that result from an excessive accumulation of collagen. The PAI-1 activity can be reduced by PAI-1 inhibitors which include but are not limited to PAI-1 neutralizing antibodies, diketopiperazine based compounds, tetramic acid based compounds, hydroxyquinolinone based compounds, Enalapril, Eprosartan, Troglitazone, Vitamin C, Vitamin E, Mifepristone (RU486), and Spironolactone to name a few. Another aspect of the present invention is directed to methods of measuring PAI-1 activity in a wound healing process and determining the propensity of the formation of an abnormal scar. Excerpt(s): This application claims the benefit of U.S. Provisional Application No.60/380,696, filed May 13, 2002, which is hereby incorporated by reference in its entirety including drawings as fully set forth herein. The present invention relates to the treatment or prevention of abnormal scar formation. Specifically, the present invention relates to the reduction of the activity of plasminogen activator inhibitor-1 to decrease an excessive deposit of collagen in a wound healing process that causes abnormal scars including keloids, hypertrophic scars, adhesions, and other cutaneous or internal wounds or lesions. Wound healing is a continuous process commonly divided into four separate phases: 1) coagulation, 2) inflammation, 3) migration and proliferation, and 4) remodeling. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

9

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

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Keeping Current In order to stay informed about patents and patent applications dealing with mifepristone, 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 “mifepristone” (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 mifepristone. You can also use this procedure to view pending patent applications concerning mifepristone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. PERIODICALS AND NEWS ON MIFEPRISTONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover mifepristone.

News Services and Press Releases One of the simplest ways of tracking press releases on mifepristone 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 “mifepristone” (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 mifepristone. 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 “mifepristone” (or synonyms). The following was recently listed in this archive for mifepristone: •

Danco says Mifeprex sales are increasing Source: Reuters Industry Breifing Date: September 24, 2002

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Use of mifepristone for abortions rises in Germany Source: Reuters Industry Breifing Date: April 08, 2002

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Abortions using mifepristone increasing in Germany Source: Reuters Medical News Date: April 08, 2002

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Corcept, maker of mifepristone depression drug, files IPO Source: Reuters Industry Breifing Date: December 24, 2001

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Woman dies in mifepristone trial Source: Reuters Industry Breifing Date: September 13, 2001

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Interval between misoprostol and mifepristone administration can be more flexible Source: Reuters Industry Breifing Date: October 17, 2000

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FDA approves mifepristone for early medical abortion Source: Reuters Industry Breifing Date: September 28, 2000

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FDA decision on mifepristone disappoints abortion rights advocates Source: Reuters Medical News Date: February 23, 2000

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FDA mifepristone letter disappoints abortion rights advocates Source: Reuters Health eLine Date: February 22, 2000

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Low-dose mifepristone plus vaginal misoprostol effective abortifacient Source: Reuters Medical News Date: April 20, 1999

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Timing of emergency contraceptives crucial, low-dose mifepristone effective Source: Reuters Medical News Date: February 26, 1999

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Misoprostol May Be Administered At Home Following Mifepristone To Induce Abortion Source: Reuters Medical News Date: April 29, 1997

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Population Council Settles Dispute With Mifepristone Handler Source: Reuters Medical News Date: February 14, 1997

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FDA Says Mifepristone Regimen "Approvable" Source: Reuters Medical News Date: September 19, 1996

•

Lower Dose Mifepristone Effective In Second Trimester Abortions Source: Reuters Medical News Date: August 21, 1996 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.

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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 “mifepristone” (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 “mifepristone” (or synonyms). If you know the name of a company that is relevant to mifepristone, 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 “mifepristone” (or synonyms).

Academic Periodicals covering Mifepristone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to mifepristone. In addition to these sources, you can search for articles covering mifepristone 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.”

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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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CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for mifepristone. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with mifepristone. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to mifepristone: Mifepristone •

Systemic - U.S. Brands: Mifeprex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500217.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

105

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 Institute10: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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.11 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:12 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “mifepristone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 3830 199 16 1 2 4048

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “mifepristone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

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

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Coffee Break: Tutorials for Biologists18 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.19 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.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

18 Adapted 19

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on mifepristone 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 mifepristone. 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 mifepristone. 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 “mifepristone”:

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Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Drug and Medical Device Safety http://www.nlm.nih.gov/medlineplus/drugandmedicaldevicesafety.html Food Safety http://www.nlm.nih.gov/medlineplus/foodsafety.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.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. 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: •

Mifepristone Information Summary: The Food and Drug Administration has approved mifepristone (trade name Mifeprex) for the termination of early pregnancy, defined as 49 days or less, counting from the beginning of the last menstrual Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7907 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 mifepristone. 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.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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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 “mifepristone”. 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 “mifepristone” (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 “mifepristone” (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.21

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

21

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)22: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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/

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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

•

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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MIFEPRISTONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] 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] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [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] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH]

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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] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] 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]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and

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herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] 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] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH]

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Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] 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] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat

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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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autosuggestion: Suggestion coming from the subject himself. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing 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] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure.

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Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of 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] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] 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 Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example,

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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] 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Broad Ligament: A broad fold of peritoneum that extends from the side of the uterus to the wall of the pelvis. [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]

Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [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] 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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is

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usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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 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 Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph

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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 Ripening: A change in the cervix with respect to its readiness to relax. The cervix becomes softer, more flexible, more distensible, and shorter in the final weeks of pregnancy. Though naturally occurring during normal pregnancy, it can also be induced for certain cases of prolonged or high-risk pregnancy by administration of hormones. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Choriocarcinoma: A malignant tumor of trophoblastic epithelium characterized by secretion of large amounts of chorionic gonadotropin. It usually originates from chorionic products of conception (i.e., hydatidiform mole, normal pregnancy, or following abortion), but can originate in a teratoma of the testis, mediastinum, or pineal gland. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic nervous system. [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] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] 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] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or

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transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [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 trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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

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'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] 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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] 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]

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Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Coumarin: A fluorescent dye. [NIH] Coumestrol: A coumarin derivative occurring naturally in forage crops which has estrogenic activity. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of

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homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [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] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists

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despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilate: Relax; expand. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] Diurnal: Occurring during the day. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Elastin: The protein that gives flexibility to tissues. [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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is

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concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [NIH] 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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers:

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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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen receptor negative: ER-. Breast cancer cells that do not have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER- do not need the hormone estrogen to grow and usually do not respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] 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] Exfoliation: A falling off in scales or layers. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the

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relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fetal Death: Death of the young developing in utero. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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

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sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [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] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g.,

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fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] 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 Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

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] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational trophoblastic disease: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic tumor, gestational trophoblastic neoplasia, molar pregnancy, or choriocarcinoma. [NIH] Gestational trophoblastic neoplasia: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic tumor, molar pregnancy, or choriocarcinoma. [NIH] Gestational trophoblastic tumor: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic neoplasia, molar pregnancy, or choriocarcinoma. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] 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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration

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following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gossypol: Poisonous pigment found in cottonseed and potentially irritating to gastrointestinal tract. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Health Care Costs: The actual costs of providing services related to the delivery of health

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care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [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 Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

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]

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Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hospital Administrators: Managerial personnel responsible for implementing policy and directing the activities of hospitals. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to

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an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterectomy: Excision of the uterus. [NIH] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] 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] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of

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psychological, physiological, or anatomical structure or function. [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] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoperable: Not suitable to be operated upon. [EU]

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Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intracellular: Inside a cell. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] 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]

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] 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]

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Islet: Cell producing insulin in pancreas. [NIH] Karyotypes: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU] Laminaria: A genus of Laminariaceae. Dried pencil-like pieces may be inserted in the cervix where they swell as they absorb moisture, and thus dilate the cervix. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together

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from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [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] 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] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [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

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diseases. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [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] Manic: Affected with mania. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious

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anaemia. [EU] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [NIH] Megestrol Acetate: A drug that belongs to the group of hormones called progestins, used as hormone therapy to block estrogen and to suppress the effects of estrogen and androgens. [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] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [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] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH]

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Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [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]

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Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molar pregnancy: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic neoplasia, gestational trophoblastic tumor, or choriocarcinoma. [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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] 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] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes

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that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular

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endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [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] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nulliparous: Having never given birth to a viable infant. [EU] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

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Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovarian Hyperstimulation Syndrome: Syndrome composed of a combination of ovarian enlargement and an acute fluid shift out of the intravascular space. The enlargement is caused by ovarian cyst formation and the fluid shift may result in ascites, hydrothorax, or generalized edema. The syndrome is most usually seen as a complication of ovulation induction, a treatment for infertility. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]

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] Paradoxical: Occurring at variance with the normal rule. [EU] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH]

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Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [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 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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight

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of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [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] Polyp: A growth that protrudes from a mucous membrane. [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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in

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the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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]

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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] 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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] 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] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [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] 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 Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or

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vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] 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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is

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both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radioactive: Giving off radiation. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]

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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [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] 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] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [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]

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Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary

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sex characteristics are those which are masculine or feminine but not directly related to reproduction. [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] Skeletal: Having to do with the skeleton (boney part of the body). [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] 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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sonogram: A computer picture of areas inside the body created by bouncing sound waves off organs and other tissues. Also called ultrasonogram or ultrasound. [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]

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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] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] 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]

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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] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in

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mammary and uterine. [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] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [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] 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] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of

Dictionary 171

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] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translating: Conversion from one language to another language. [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] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10

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megahertz. [NIH] Unresectable: Unable to be surgically removed. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] Virilism: Development of masculine traits in the female. [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

Dictionary 173

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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [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] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [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]

175

INDEX A Abdominal, 123, 129, 131, 158, 159, 165 Aberrant, 10, 123 Ablate, 22, 25, 123 Acceptor, 123, 150, 157 Acetylcholine, 123, 131, 155, 156 Adaptability, 123, 130 Adaptation, 123, 154, 160 Adenine, 123 Adenocarcinoma, 47, 123 Adenosine, 87, 123, 159 Adenosine Monophosphate, 87, 123 Adenovirus, 12, 123 Adhesions, 94, 123 Adipocytes, 123, 133, 149 Adjuvant, 5, 124 Adrenal Cortex, 17, 124, 134, 139, 145, 156, 161 Adrenal Glands, 27, 124 Adrenal Medulla, 124, 130, 131, 139, 156, 158 Adrenergic, 39, 124, 137, 139, 169 Adverse Effect, 23, 58, 124, 167 Afferent, 19, 124, 149, 161 Affinity, 124, 127, 167 Agar, 124, 159 Agonist, 20, 22, 26, 87, 93, 124, 137, 169 Aldosterone, 27, 124 Algorithms, 124, 128 Alkaline, 124, 125, 129 Allantois, 124, 140 Alpha Particles, 124, 164 Alternative medicine, 99, 124 Amenorrhea, 17, 125, 160 Amino Acid Sequence, 125, 126 Ammonia, 125, 143 Amnion, 125, 140 Amyloid, 18, 125 Anaesthesia, 125, 147 Analog, 125, 153 Analogous, 5, 15, 125, 160, 171 Anatomical, 125, 127, 147, 153, 155 Androgenic, 125, 135 Androgens, 124, 125, 145, 152 Angiogenesis, 9, 125, 151 Animal model, 12, 86, 125 Anorexia, 18, 125 Anorexia Nervosa, 18, 125

Anovulation, 125, 160 Antecedent, 15, 126 Antiandrogens, 87, 126 Antibiotic, 10, 126, 168, 170 Antibodies, 7, 10, 94, 126, 145, 146, 150, 159 Antibody, 14, 124, 126, 132, 144, 146, 147, 154, 164, 168 Anticoagulant, 126, 162 Antigen, 124, 126, 133, 144, 145, 146, 147, 153, 161 Anti-inflammatory, 82, 126, 142, 147 Antimetabolite, 126, 136, 153 Antineoplastic, 126, 153 Antioxidant, 126, 157 Anus, 126, 132 Anxiety, 86, 126 Aorta, 26, 126, 161, 172 Apolipoproteins, 126, 150 Apoptosis, 9, 14, 27, 30, 50, 51, 126 Aqueous, 126, 135 Arachidonic Acid, 49, 126, 162 Arginine, 84, 127, 155 Arterial, 12, 127, 131, 134, 145, 162 Arteries, 126, 127, 128, 129, 134, 150, 153, 154, 163, 170 Arterioles, 127, 129, 172 Artery, 127, 134, 163 Ascites, 60, 127, 157 Aspiration, 32, 38, 59, 62, 64, 127 Assay, 19, 21, 81, 127 Astrocytes, 20, 127, 151, 153 Atrial, 127, 134, 171 Atrioventricular, 127, 134 Atrium, 127, 134, 171, 172 Auditory, 127, 161 Autonomic, 15, 123, 127, 156, 158, 167, 169 Autonomic Nervous System, 15, 127, 158, 167, 169 Autosuggestion, 127, 146 B Bacteria, 126, 127, 128, 140, 150, 153, 168, 171, 172 Bactericidal, 127, 139 Bacteriophage, 127, 159, 171 Baroreflex, 12, 127 Benign, 53, 128, 135, 140, 149, 155, 164 Beta-pleated, 125, 128

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Bilateral, 128, 160 Bile, 28, 128, 150, 168 Bile Acids, 128, 168 Bile Acids and Salts, 128 Binding Sites, 24, 128 Biochemical, 49, 83, 84, 85, 86, 87, 126, 128, 140 Biological therapy, 128, 143 Biopsy, 17, 128, 133 Biosynthesis, 19, 127, 128 Biotechnology, 31, 99, 107, 128 Bladder, 26, 128, 162, 172 Blastocyst, 128, 133, 159 Blood Coagulation, 128, 129, 170 Blood Glucose, 128, 144, 146, 148 Blood pressure, 12, 127, 128, 130, 145, 154, 163, 167 Blood vessel, 9, 124, 125, 128, 129, 130, 134, 138, 149, 150, 158, 167, 168, 170, 172 Body Fluids, 129, 167 Bone Marrow, 129, 141, 150, 151, 154, 167, 168 Bradykinin, 129, 156 Broad Ligament, 129, 140 Buffers, 127, 129 C Cachexia, 8, 17, 129 Caesarean section, 67, 129 Calcium, 25, 129, 132, 151, 162 Calcium Channels, 25, 129 Callus, 129, 138 Carbon Dioxide, 129, 159, 165 Carcinogenic, 129, 147, 161, 168, 171 Carcinogens, 129, 173 Carcinoma, 47, 49, 61, 87, 129 Cardiac, 27, 128, 129, 134, 139, 154, 168 Cardiac Output, 128, 129 Cardiomyopathy, 27, 130 Cardiovascular, 11, 15, 24, 28, 129, 130, 167 Cardiovascular disease, 11, 24, 28, 130 Catecholamine, 130, 136 Caudal, 130, 136, 146, 160 Cause of Death, 13, 20, 130 Cell, 3, 6, 7, 8, 9, 10, 13, 14, 17, 22, 24, 25, 26, 27, 30, 47, 48, 52, 65, 78, 83, 84, 85, 86, 87, 92, 124, 126, 127, 128, 129, 130, 131, 132, 133, 135, 136, 138, 139, 140, 141, 143, 144, 145, 146, 147, 148, 149, 151, 152, 153, 154, 155, 157, 159, 160, 161, 162, 163, 164, 165, 166, 168, 170, 171, 173

Cell Cycle, 30, 85, 130, 132, 135, 161, 163 Cell Death, 4, 9, 126, 130, 155 Cell Division, 127, 130, 143, 152, 153, 159, 162, 166 Cell membrane, 129, 130, 159, 173 Cell proliferation, 4, 14, 130, 157 Cell Size, 130, 141 Cell Survival, 27, 30, 130, 143 Central Nervous System, 12, 123, 127, 128, 129, 130, 143, 153 Centrifugation, 130, 153 Cerebral, 18, 20, 130, 139, 140, 141 Cerebrovascular, 130 Cerebrum, 130 Cervical, 5, 7, 14, 36, 37, 38, 39, 49, 50, 57, 59, 62, 83, 86, 130, 131, 133 Cervical Ripening, 5, 49, 50, 57, 83, 86, 131 Cervix, 7, 14, 39, 46, 49, 60, 63, 70, 123, 131, 133, 149 Cesarean Section, 82, 83, 131 Chemokines, 4, 7, 131 Chemoprevention, 5, 131 Chemotherapy, 8, 28, 131 Cholera, 131, 166 Cholesterol, 24, 28, 128, 131, 132, 134, 145, 150, 152, 168, 169 Cholesterol Esters, 131, 150 Choline, 8, 131 Choriocarcinoma, 131, 142, 154 Chorion, 131, 140 Chromaffin Cells, 84, 131, 158 Chromatin, 126, 131, 155 Chromic, 131 Chromosome, 131, 149, 166 Chronic, 15, 27, 129, 131, 138, 147, 149, 160, 166, 168 Chronic Disease, 129, 131, 149 Chronic renal, 131, 160 Chylomicrons, 132, 150 Cicatrix, 82, 132 Circadian, 14, 132 Circadian Rhythm, 14, 132 Cisplatin, 47, 132 Clinical trial, 3, 21, 30, 35, 40, 48, 66, 107, 132, 134, 137, 162, 164 Clone, 23, 132 Cloning, 128, 132 Cofactor, 132, 162, 170 Collagen, 7, 14, 94, 125, 132, 140, 148, 151, 160, 161 Colon, 26, 132 Combinatorial, 22, 132

177

Complement, 132, 133, 149 Complementary and alternative medicine, 81, 89, 133 Complementary medicine, 81, 133 Computational Biology, 107, 133 Conception, 123, 131, 133, 140, 142, 154, 168 Concomitant, 7, 133 Cone, 67, 133 Cone biopsy, 67, 133 Conization, 133 Conjugated, 128, 133, 135 Connective Tissue, 7, 129, 132, 133, 140, 150, 168 Connective Tissue Cells, 133 Consciousness, 133, 136 Contraceptive, 29, 32, 34, 42, 43, 48, 56, 57, 59, 71, 133, 151, 156 Contractility, 14, 73, 134 Contraindications, ii, 134 Control group, 23, 134 Controlled study, 17, 34, 53, 57, 134 Cor, 14, 134 Cornea, 134, 168 Coronary, 130, 134, 153, 154 Coronary heart disease, 130, 134 Coronary Thrombosis, 134, 153, 154 Corpus, 134, 150, 161 Corpus Luteum, 134, 150, 161 Cortex, 15, 134, 140, 161 Cortical, 15, 17, 134, 139, 161 Cortisol, 14, 15, 18, 43, 64, 134 Coumarin, 134 Coumestrol, 83, 134 Crossing-over, 134, 164 Cultured cells, 24, 135 Curative, 135, 170 Curettage, 35, 42, 43, 59, 135 Curette, 135 Cutaneous, 94, 135 Cyclic, 87, 135, 143, 156 Cyclin, 18, 135 Cyst, 135, 157 Cysteine, 131, 135, 169 Cytochrome, 28, 54, 135 Cytokine, 4, 7, 10, 135 Cytoplasm, 22, 126, 130, 135, 154, 155, 165 Cytoprotection, 28, 135 Cytotoxic, 13, 135, 146, 164 Cytotoxicity, 68, 132, 135 D Danazol, 7, 41, 68, 135

Decidua, 59, 70, 74, 135, 159 Deletion, 126, 135 Delivery of Health Care, 135, 144 Delusions, 135, 163 Dendrites, 136, 155 Density, 12, 130, 136, 141, 150, 157, 167 Deoxyribonucleic, 136, 165 Deoxyuridine, 14, 136 Desensitization, 136, 146 Diabetes Mellitus, 15, 136, 143, 144 Diagnostic procedure, 91, 99, 136 Diencephalon, 136, 146, 161, 170 Digestion, 128, 136, 150, 168 Dihydrotestosterone, 136, 164 Dilate, 136, 149 Dilated cardiomyopathy, 27, 136 Dilation, 56, 129, 136 Direct, iii, 5, 9, 28, 101, 136, 137, 165, 169 Disinfectant, 136, 139 Dissociation, 7, 124, 136 Dissociative Disorders, 136 Distal, 7, 136 Diurnal, 21, 136 Dopamine, 14, 136, 155, 159 Dorsal, 11, 137, 160 Dorsum, 137 Double-blind, 17, 23, 33, 34, 43, 49, 50, 51, 53, 70, 137 Double-blinded, 23, 33, 137 Drive, ii, vi, 8, 28, 77, 137 Drug Interactions, 11, 84, 102, 137 Duodenum, 128, 137, 168 Dyes, 125, 137, 141, 155 Dysmenorrhea, 6, 137 Dystrophy, 82, 137 E Ectopic Pregnancy, 56, 137 Edema, 20, 137, 157 Efficacy, 12, 24, 32, 33, 35, 38, 42, 66, 73, 75, 78, 137 Elastin, 132, 137, 140 Elective, 33, 137 Electrolyte, 124, 137, 153, 160, 167 Electron microscope, 39, 137 Electrons, 126, 137, 148, 157, 164 Electrophysiological, 6, 137 Embryo, 123, 125, 128, 138, 140, 147, 156, 160, 173 Embryogenesis, 6, 138 Embryology, 138, 140 Endocrine System, 138, 155

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Endocrinology, 21, 28, 42, 43, 44, 45, 53, 54, 63, 66, 68, 69, 70, 71, 78, 84, 86, 87, 138 Endogenous, 14, 19, 28, 136, 138, 171 Endometrial, 7, 17, 23, 32, 45, 46, 52, 53, 54, 71, 138 Endometrium, 7, 9, 17, 29, 37, 44, 47, 61, 63, 66, 70, 135, 138 Endothelial cell, 8, 138, 170 Endothelium, 138, 155, 160 Endothelium-derived, 138, 155 End-stage renal, 131, 138, 160 Energy balance, 138, 149 Enhancer, 36, 138 Enterocytes, 84, 138 Environmental Health, 11, 106, 108, 138 Enzymatic, 125, 129, 133, 138, 152, 165 Enzyme, 8, 16, 25, 49, 138, 142, 143, 147, 150, 158, 160, 162, 164, 165, 170, 173 Epidemic, 13, 138 Epidermal, 72, 138 Epidermis, 138 Epinephrine, 124, 131, 136, 139, 155, 156, 171 Epithelial, 7, 14, 30, 63, 123, 135, 139, 143 Epithelial Cells, 7, 63, 139 Epithelium, 14, 30, 83, 131, 138, 139 Erythrocytes, 87, 129, 139 Esophagus, 139, 168 Estradiol, 7, 19, 21, 66, 139 Estrogen, 9, 14, 17, 19, 27, 32, 45, 50, 57, 93, 139, 152, 161, 166, 169 Estrogen receptor, 17, 19, 50, 139 Estrogen receptor negative, 50, 139 Ethanol, 10, 139 Eukaryotic Cells, 139, 147, 157 Evacuation, 36, 56, 139, 158 Excitation, 139, 140, 155 Excitatory, 139, 143 Exfoliation, 139, 154 Exogenous, 9, 12, 14, 19, 24, 138, 139 Extracellular, 125, 127, 133, 139, 140, 151, 153, 167 Extracellular Matrix, 133, 139, 140, 151 Extracellular Matrix Proteins, 139, 151 Extrapyramidal, 137, 140 Eye Infections, 123, 140 F Fallopian tube, 45, 63, 140 Family Planning, 37, 56, 72, 107, 140 Fat, 123, 126, 128, 129, 134, 140, 149, 150 Fatigue, 140, 144

Fetal Death, 51, 140 Fetal Heart, 35, 140 Fetal Membranes, 42, 140 Fetus, 123, 131, 140, 159, 161, 172 Fibril, 7, 140 Fibrinogen, 140, 160, 170 Fibroblasts, 133, 140, 148 Fibroid, 23, 93, 140, 149 Fibrosis, 94, 140 Fissure, 140, 161 Flow Cytometry, 10, 140 Fluorescence, 140, 141 Fluorescent Dyes, 140, 141 Folate, 136, 141 Fold, 24, 28, 129, 140, 141 Follicles, 141, 147 Foramen, 141, 158 Forearm, 129, 141 Free Radicals, 126, 136, 141 Frontal Lobe, 141, 161 Functional magnetic resonance imaging, 15, 141 G Gangrenous, 141, 166 Gas, 125, 129, 141, 145, 155, 156, 169 Gastric, 47, 65, 141, 153 Gastric Acid, 141, 153 Gastrin, 141, 145 Gastrointestinal, 129, 139, 140, 141, 143, 149, 167, 169 Gastrointestinal tract, 139, 140, 141, 143, 149, 167 Gene, 4, 7, 9, 19, 22, 24, 25, 26, 27, 63, 65, 81, 82, 83, 84, 85, 123, 128, 141, 157, 160, 166, 171 Gene Expression, 4, 10, 19, 24, 25, 27, 63, 65, 82, 83, 85, 141 Gene Therapy, 24, 123, 141 Generator, 21, 142 Genetic Screening, 27, 142 Genetics, 24, 78, 142 Genital, 142, 172 Genomics, 28, 142 Germ Cells, 142, 152, 157, 170, 173 Gestation, 32, 33, 43, 55, 57, 61, 142, 159 Gestational, 142, 154 Gestational trophoblastic disease, 142, 154 Gestational trophoblastic neoplasia, 142, 154 Gestational trophoblastic tumor, 142, 154 Ginseng, 84, 142

179

Gland, 22, 124, 131, 142, 145, 150, 151, 158, 162, 166, 168, 170 Glucocorticoid, 4, 10, 11, 13, 14, 16, 19, 27, 30, 69, 82, 84, 85, 86, 92, 142 Glucose, 4, 128, 136, 142, 144, 148, 166 Glucose Intolerance, 136, 142 Glutamate, 143 Glutamic Acid, 20, 143, 155, 161 Glutamine, 84, 143 Glycerol, 143, 159 Glycerophospholipids, 143, 159 Glycine, 125, 128, 143, 155 Glycoprotein, 52, 83, 140, 143, 170 Goblet Cells, 138, 143 Gonad, 143 Gonadal, 17, 21, 143, 168 Gonadotropin, 21, 131, 143 Gossypol, 41, 143 Governing Board, 143, 161 Graft, 9, 143 Grafting, 143, 147 Granulosa Cells, 143, 147, 150 Growth factors, 9, 22, 143, 153, 157 Guanylate Cyclase, 143, 156 H Haemorrhage, 123, 143 Health Care Costs, 23, 143, 144 Health Education, 86, 144 Health Expenditures, 144 Health Status, 23, 144 Heart attack, 130, 144 Heart failure, 28, 144 Hematology, 29, 144 Heme, 135, 144 Hemoglobin, 139, 144 Hemoglobinopathies, 142, 144 Hepatic, 12, 49, 144 Hepatocyte, 84, 85, 144 Hepatoma, 83, 144 Heredity, 141, 142, 144 Hirsutism, 144, 145 Histology, 8, 144 Homeostasis, 6, 144, 167 Homodimer, 144, 171 Homologous, 135, 141, 144, 163, 166, 169 Hormonal, 46, 78, 131, 144 Hormone, 5, 11, 18, 20, 21, 22, 26, 45, 48, 49, 68, 70, 86, 92, 93, 124, 132, 134, 139, 141, 144, 145, 147, 148, 149, 151, 152, 161, 165, 167, 170, 171 Hormone Replacement Therapy, 5, 145 Hormone therapy, 145, 152

Hospital Administrators, 30, 145 Hybrid, 23, 132, 145 Hybridomas, 145, 148 Hydrogen, 123, 129, 139, 145, 150, 154, 155, 157, 163 Hydrolysis, 132, 145, 150, 160 Hydrophobic, 143, 145, 150 Hydroxylysine, 132, 145 Hydroxyproline, 125, 132, 145 Hyperandrogenism, 21, 145 Hypercholesterolemia, 12, 24, 145 Hyperglycemia, 4, 145 Hyperlipidemia, 4, 145 Hyperplasia, 23, 53, 145 Hypersensitivity, 10, 136, 145 Hyperstimulation, 14, 145 Hypertension, 130, 145 Hypertrophy, 134, 145, 171 Hypoglycemia, 15, 146 Hypoglycemic, 15, 146 Hypothalamic, 15, 18, 20, 146 Hypothalamus, 22, 127, 136, 146, 149, 167 Hypoxia, 8, 146 Hypoxic, 8, 146 Hysterectomy, 93, 146 Hysterotomy, 131, 146 I Iatrogenic, 15, 146 Immune function, 10, 146, 171 Immune response, 27, 124, 126, 146, 169, 173 Immune system, 128, 146, 150, 151, 173 Immunodeficiency, 92, 146 Immunoglobulin, 126, 146, 154 Immunohistochemistry, 12, 14, 18, 146 Immunologic, 146, 151, 164 Immunology, 124, 141, 146 Immunosuppressant, 146, 153 Immunosuppression, 10, 12, 146, 151 Immunosuppressive, 142, 146 Immunosuppressive Agents, 146 Impairment, 140, 146, 152, 163 Implantation, 46, 47, 61, 70, 133, 147, 156 In situ, 10, 19, 147 In Situ Hybridization, 10, 19, 147 In vitro, 5, 7, 10, 19, 20, 26, 27, 45, 47, 49, 81, 84, 141, 147, 170 In vivo, 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, 20, 26, 27, 30, 47, 73, 78, 141, 147, 151, 170 Incision, 129, 146, 147, 148 Incubated, 5, 147 Indomethacin, 73, 147

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Mifepristone

Infarction, 147 Infection, 13, 128, 140, 146, 147, 150, 166, 169, 173 Infertility, 7, 20, 93, 147, 157 Inflammation, 94, 126, 140, 141, 147, 160, 165 Infusion, 10, 147 Inhibin, 17, 147 Initiation, 147, 171 Inoperable, 68, 147 Inorganic, 132, 148, 154 Inotropic, 137, 148 Insecticides, 148, 173 Insight, 23, 148 Insulin, 36, 70, 148, 149 Insulin-dependent diabetes mellitus, 148 Insulin-like, 36, 70, 148 Interferon, 7, 148 Interferon-alpha, 148 Interleukin-6, 10, 148 Intermittent, 29, 148 Interstitial, 83, 148 Interstitial Collagenase, 83, 148 Intestinal, 138, 148, 173 Intracellular, 19, 22, 147, 148, 152, 156, 160 Intravascular, 148, 157 Intravenous, 147, 148 Invasive, 47, 148, 151 Ion Channels, 6, 127, 148 Ions, 129, 136, 137, 145, 148 Islet, 4, 149 K Karyotypes, 142, 149 Kb, 106, 149 Kinetic, 24, 149 L Lactation, 83, 149, 156, 161 Laminaria, 65, 149 Latent, 149, 161 Leiomyoma, 140, 149, 167 Leptin, 19, 149 Lethal, 24, 82, 127, 149 Leucocyte, 149 Leukaemia, 71, 149 Leukemia, 142, 149 Leukocytes, 129, 131, 147, 148, 149, 154, 155 Levonorgestrel, 17, 29, 44, 45, 47, 53, 59, 65, 149, 156 Ligament, 149, 162 Ligands, 12, 28, 149 Limbic, 149, 161

Limbic System, 149, 161 Linkage, 28, 149 Lipid, 37, 126, 131, 143, 148, 150, 158 Lipid Peroxidation, 150, 158 Lipolysis, 18, 150 Lipoprotein, 12, 150 Liver, 18, 24, 49, 54, 85, 123, 127, 128, 144, 150, 158 Localization, 146, 150 Localized, 6, 144, 147, 150, 159, 166, 171 Loop, 22, 150 Low-density lipoprotein, 150 Luciferase, 7, 25, 150 Luteal Phase, 36, 57, 61, 70, 150 Lutein Cells, 150, 161 Lymph, 130, 138, 150 Lymph node, 131, 150 Lymphatic, 138, 147, 150, 167 Lymphatic system, 150, 167 Lymphocyte, 126, 146, 150, 151 Lymphocyte Depletion, 146, 151 Lymphoid, 126, 149, 151 Lymphokines, 151 M Macroglia, 151, 153 Macrophage, 10, 85, 151 Macrophage Activation, 85, 151 Magnetic Resonance Imaging, 151 Malignant, 8, 30, 123, 126, 131, 151, 155, 161, 164 Malnutrition, 18, 129, 151 Mammary, 22, 30, 83, 151, 170 Manic, 151, 163 Mastitis, 151, 166 Matrix metalloproteinase, 9, 70, 151 Mediate, 6, 13, 19, 28, 137, 151 Medical Oncology, 151, 164 Medical Staff, 137, 151 MEDLINE, 107, 151 Medroxyprogesterone, 46, 57, 151 Medroxyprogesterone Acetate, 46, 57, 151 Megaloblastic, 136, 151 Megestrol, 67, 152 Megestrol Acetate, 67, 152 Meiosis, 152, 169 Melanin, 152, 159, 171 Membrane, 25, 125, 127, 130, 131, 133, 139, 148, 152, 154, 157, 159, 160, 162, 165, 173 Membrane Lipids, 152, 159 Memory, 24, 125, 152 Meninges, 130, 152 Meningioma, 68, 152

181

Menopause, 20, 152, 156 Menstruation, 9, 43, 93, 125, 135, 137, 150, 152, 157 Mental, iv, 3, 106, 108, 136, 140, 152, 163, 166 Mental Disorders, 152, 163 Mental Processes, 136, 152, 163 Mercury, 140, 152 Metabolite, 4, 152 Metastasis, 8, 151, 152 Metastatic, 47, 61, 152, 166 Methionine, 16, 152, 169 Methotrexate, 32, 36, 37, 39, 41, 55, 56, 153 MI, 53, 121, 153 Microbe, 153, 170 Microglia, 25, 127, 153 Microorganism, 132, 153, 173 Microsomal, 54, 153 Migration, 18, 94, 151, 153 Mineralocorticoids, 124, 153 Mitogen-Activated Protein Kinase Kinases, 153 Mitogen-Activated Protein Kinases, 82, 153 Mitosis, 126, 153 Mitotic, 93, 153 Modification, 125, 154, 163 Molar pregnancy, 68, 142, 154 Molecular, 3, 4, 6, 7, 8, 9, 13, 21, 22, 24, 26, 28, 45, 67, 70, 81, 83, 84, 107, 109, 128, 133, 140, 154, 159, 160, 161 Molecule, 126, 128, 133, 135, 136, 138, 139, 144, 145, 154, 157, 164, 172 Monitor, 154, 156 Monoclonal, 14, 145, 154 Monocytes, 6, 148, 149, 154 Mononuclear, 154 Monophosphate, 87, 154 Morphological, 4, 138, 154 Morphology, 7, 144, 151, 154 Motility, 147, 154 Mucins, 138, 143, 154 Mucosa, 138, 154, 161, 168, 173 Mucus, 38, 154 Multidrug resistance, 65, 154 Muscle Fibers, 6, 154 Muscular Dystrophies, 137, 154 Mydriatic, 136, 154 Myocardial infarction, 24, 134, 153, 154 Myocardium, 153, 154 N Necrolysis, 72, 154

Necrosis, 126, 147, 153, 154 Neonatal, 57, 78, 155 Neoplasia, 155 Neoplasm, 155 Neoplastic, 27, 145, 155, 157 Nerve, 12, 84, 124, 136, 155, 168, 171 Nervous System, 124, 127, 130, 131, 155, 158, 169 Networks, 15, 155 Neural, 11, 20, 124, 125, 153, 155 Neuroendocrine, 4, 16, 20, 21, 155 Neuroendocrinology, 21, 155 Neuromuscular, 6, 82, 123, 155 Neuromuscular Junction, 6, 123, 155 Neuronal, 12, 19, 20, 129, 155 Neurons, 12, 19, 136, 139, 155, 169 Neuropeptide, 19, 155 Neurotransmitter, 123, 125, 129, 136, 143, 148, 155, 156, 167, 169 Neutrons, 124, 155, 164 Neutrophils, 5, 149, 155 Nitric Oxide, 4, 47, 155 Nitrogen, 125, 139, 143, 156, 171 Norepinephrine, 124, 136, 155, 156 Norgestrel, 149, 156 Nuclear, 19, 28, 137, 139, 149, 155, 156, 157, 161, 170 Nuclei, 92, 124, 137, 141, 149, 151, 153, 155, 156, 163 Nucleic acid, 147, 156, 165 Nucleus, 22, 92, 126, 131, 135, 139, 152, 154, 155, 156, 161, 162, 163, 167 Nulliparous, 59, 156 Nurse Practitioners, 57, 156 O Observational study, 31, 47, 156 Oestrogen, 48, 59, 156 Oligomenorrhea, 157, 160 Oncogenes, 11, 157, 163 Oncology, 29, 30, 50, 61, 87, 157 Opacity, 136, 157 Operon, 157, 165 Optic Chiasm, 146, 157 Organ Culture, 157, 170 Organelles, 130, 135, 154, 157 Osteoporosis, 156, 157 Ovarian Hyperstimulation Syndrome, 60, 157 Ovaries, 17, 145, 157, 160, 165, 166 Ovary, 134, 139, 143, 156, 157, 160, 168 Ovulation, 17, 20, 22, 43, 52, 125, 143, 150, 152, 156, 157

182

Mifepristone

Ovulation Induction, 157 Ovum, 134, 135, 142, 157, 161, 173 Oxidation, 49, 123, 126, 135, 150, 157, 158 Oxidative Stress, 16, 20, 157 Oxytocic, 153, 158 P Palliative, 152, 156, 158, 170 Pancreas, 123, 148, 149, 158, 167 Paradoxical, 17, 158 Paraganglia, Chromaffin, 131, 158 Particle, 158, 167, 171 Parturition, 158, 161 Pathogenesis, 4, 11, 158 Pathologic, 126, 128, 134, 145, 158 Pathologic Processes, 126, 158 Pathophysiology, 14, 18, 27, 158 Pelvic, 6, 93, 158, 162 Pelvis, 129, 157, 158, 172 Pepsin, 153, 158 Peptide, 16, 19, 22, 60, 125, 149, 158, 160, 162 Perception, 41, 133, 158 Perfusion, 146, 158 Peripheral Nervous System, 155, 158, 167, 169 Peritoneal, 6, 127, 158 Peritoneal Cavity, 6, 127, 158 Peritoneum, 129, 158, 159, 165 Perivascular, 153, 159 Phagocytosis, 25, 153, 159 Pharmacokinetic, 43, 159 Pharmacologic, 159, 170 Phenylalanine, 159, 171 Phospholipids, 25, 140, 150, 152, 159, 162 Phosphorus, 129, 159 Phosphorylation, 22, 82, 153, 159, 162 Physiologic, 4, 124, 128, 152, 159, 164 Physiology, 16, 26, 67, 123, 137, 138, 144, 159 Pigment, 143, 159 Pilot study, 17, 32, 61, 159 Placenta, 42, 59, 70, 139, 159, 161 Plants, 129, 131, 142, 154, 156, 159, 160, 166, 171 Plaque, 18, 159 Plasma, 10, 15, 25, 43, 126, 130, 131, 140, 142, 144, 153, 159, 160, 166, 172 Plasma cells, 126, 159 Plasmin, 159, 160 Plasminogen, 94, 159, 160 Plasminogen Activators, 159, 160 Plasticity, 6, 10, 160

Platelet Aggregation, 156, 160, 170 Platelets, 9, 156, 160, 170 Platinum, 132, 150, 160 Pneumonia, 134, 160 Pollen, 160, 163 Polycystic, 21, 145, 160 Polycystic Ovary Syndrome, 21, 145, 160 Polymerase, 160, 165 Polyp, 53, 160 Polypeptide, 125, 132, 140, 159, 160, 161, 167, 173 Polysaccharide, 126, 160, 162 Posterior, 137, 158, 160 Postnatal, 160, 168 Potassium, 124, 153, 160 Potentiates, 86, 161 Practice Guidelines, 108, 161 Precursor, 127, 131, 136, 138, 156, 159, 160, 161, 171 Predisposition, 15, 161 Prefrontal Cortex, 15, 161 Prenatal, 138, 142, 161 Pressoreceptors, 128, 161 Prevalence, 6, 13, 161 Progestogen, 9, 161 Progression, 8, 13, 15, 30, 67, 125, 161, 172 Projection, 156, 161 Prolactin, 70, 83, 161 Proliferating Cell Nuclear Antigen, 14, 161 Proline, 132, 145, 161 Promoter, 7, 25, 161 Prophase, 162, 169 Prospective study, 64, 162 Prostaglandins, 35, 37, 38, 127, 147, 162 Prostaglandins A, 147, 162 Prostaglandins F, 162 Prostate, 37, 49, 51, 87, 156, 162 Protein C, 11, 23, 27, 125, 126, 127, 150, 162 Protein Kinase C, 153, 162 Protein Kinases, 153, 157, 162 Protein S, 7, 18, 128, 162, 165, 170 Protein-Serine-Threonine Kinases, 153, 162 Proteoglycans, 7, 140, 162 Protocol, 12, 16, 162 Protons, 124, 145, 163, 164 Proto-Oncogenes, 157, 163 Psychiatric, 13, 15, 27, 152, 163 Psychiatry, 13, 14, 37, 163 Psychology, 136, 163 Psychopharmacology, 15, 64, 163

183

Psychosis, 64, 142, 163 Puberty, 20, 163 Public Policy, 107, 163 Publishing, 31, 163 Pulmonary, 128, 134, 163, 172 Pulmonary Artery, 128, 163, 172 Pulmonary hypertension, 134, 163 Pulse, 21, 154, 163 Pupil, 134, 136, 154, 163 Q Quality of Life, 23, 163 Quercetin, 85, 163 R Race, 149, 153, 156, 163, 164 Racemic, 149, 156, 164 Radiation, 8, 31, 141, 146, 164, 173 Radiation Oncology, 31, 164 Radioactive, 145, 147, 156, 164, 171 Radiology, 164 Radiopharmaceutical, 142, 164 Radiotherapy, 164 Randomized, 17, 23, 29, 32, 33, 34, 39, 43, 49, 50, 51, 53, 55, 57, 62, 64, 69, 70, 74, 137, 164 Randomized clinical trial, 33, 55, 69, 164 Reagent, 24, 150, 164 Reality Testing, 163, 164 Receptivity, 46, 164 Recombinant, 45, 164, 172 Recombination, 84, 141, 164 Recovery of Function, 20, 164 Rectum, 126, 132, 141, 162, 164 Recurrence, 8, 131, 132, 164 Reductase, 16, 153, 164 Refer, 1, 132, 150, 155, 163, 165 Refractory, 68, 87, 165 Regimen, 33, 41, 42, 46, 56, 65, 71, 98, 137, 165 Relaxin, 14, 165 Remission, 164, 165 Repressor, 27, 157, 165 Respiration, 129, 140, 154, 165 Retinal, 133, 157, 165 Retreatment, 63, 165 Retrograde, 6, 165 Retroperitoneal, 124, 165 Retrospective, 60, 165 Retroviral vector, 141, 165 Rhinitis, 165, 166 Ribonuclease, 19, 165 Ribonucleic acid, 86, 165 Ribose, 123, 165

Ribosome, 165, 171 Risk factor, 10, 162, 166 Rutin, 163, 166 S Saponins, 166, 168 Scleroderma, 94, 166 Screening, 28, 83, 132, 142, 166 Secondary tumor, 152, 166 Secretion, 6, 21, 131, 132, 145, 147, 148, 149, 153, 154, 166, 171 Secretory, 71, 93, 131, 166 Secretory Vesicles, 131, 166 Segregation, 164, 166 Selective estrogen receptor modulator, 166, 169 Semen, 162, 166 Seminiferous tubule, 147, 166 Senescence, 16, 166 Septicaemia, 166 Serotypes, 12, 166 Serum, 15, 24, 30, 72, 132, 143, 150, 151, 153, 166 Sex Characteristics, 125, 156, 163, 166, 170 Side effect, 67, 93, 101, 124, 128, 167, 170 Skeletal, 25, 125, 154, 167 Skeleton, 167 Skull, 167, 170 Small intestine, 132, 137, 145, 167 Smooth muscle, 26, 39, 133, 140, 149, 162, 167, 169 Smooth Muscle Tumor, 140, 167 Social Environment, 163, 167 Sodium, 44, 124, 153, 167 Solid tumor, 8, 125, 167 Solitary Nucleus, 127, 167 Solvent, 139, 143, 167 Somatic, 138, 149, 152, 153, 158, 161, 167 Somatostatin, 18, 167 Sonogram, 41, 167 Sound wave, 167 Specialist, 113, 136, 168 Species, 7, 14, 16, 22, 28, 139, 145, 149, 152, 153, 154, 163, 168, 169, 172, 173 Specificity, 17, 25, 124, 129, 168 Spectroscopic, 8, 168 Spectrum, 153, 168 Sperm, 87, 125, 131, 160, 166, 168 Sphincter, 7, 168 Spinal cord, 127, 130, 131, 152, 155, 158, 168, 169 Stem Cells, 9, 168

184

Mifepristone

Sterility, 32, 36, 37, 40, 42, 45, 46, 47, 62, 71, 72, 147, 168 Steroid, 7, 11, 19, 21, 22, 26, 45, 70, 72, 85, 92, 93, 128, 134, 135, 156, 166, 168 Stimulants, 142, 168 Stimulus, 134, 137, 139, 148, 168 Stomach, 18, 19, 123, 139, 141, 145, 158, 167, 168 Stool, 132, 168 Stress, 4, 10, 12, 15, 26, 27, 127, 130, 131, 134, 153, 157, 161, 168 Stroke, 106, 130, 168 Stroma, 7, 168 Stromal, 7, 14, 168 Stromal Cells, 7, 14, 168 Subacute, 147, 168 Subclinical, 147, 169 Subcutaneous, 29, 123, 137, 141, 149, 169 Sublingual, 32, 33, 61, 169 Subspecies, 168, 169 Substance P, 152, 161, 166, 169 Suction, 35, 59, 169 Sulfur, 139, 152, 169 Suppression, 29, 136, 169 Suppressive, 29, 169 Sympathetic Nervous System, 127, 131, 169 Sympathomimetic, 137, 139, 156, 169 Symphysis, 162, 169 Symptomatic, 23, 169 Synapse, 6, 124, 155, 169, 171 Synaptic, 6, 155, 169 Synergistic, 68, 161, 169 Systemic, 12, 20, 102, 126, 128, 139, 147, 166, 169, 171, 172 T Tamoxifen, 5, 7, 23, 34, 36, 51, 78, 166, 169 Temporal, 29, 170 Testicular, 17, 170 Testis, 17, 131, 139, 156, 170 Testosterone, 27, 83, 164, 170 Tetracycline, 9, 170 Thalamus, 136, 149, 161, 170 Therapeutics, 54, 88, 102, 170 Thermal, 10, 136, 155, 170 Thrombin, 140, 160, 162, 170 Thrombocytes, 160, 170 Thrombolytic, 160, 170 Thrombomodulin, 162, 170 Thrombosis, 162, 168, 170 Thromboxanes, 127, 170 Thyroid, 36, 170, 171

Tissue, 7, 9, 17, 19, 22, 24, 25, 26, 72, 93, 123, 125, 126, 128, 129, 132, 133, 135, 137, 138, 140, 141, 143, 145, 146, 148, 149, 150, 151, 152, 154, 155, 158, 159, 160, 165, 167, 168, 169, 170, 173 Tissue Culture, 22, 170 Topical, 85, 139, 170 Toxic, iv, 11, 72, 135, 170 Toxicity, 11, 27, 137, 152, 170 Toxicology, 27, 60, 83, 108, 170 Toxins, 126, 129, 147, 171 Trachea, 170, 171 Transcription Factors, 5, 22, 26, 27, 157, 171 Transduction, 4, 171 Transfection, 25, 128, 141, 171 Transforming Growth Factor beta, 17, 171 Transgenes, 24, 171 Translating, 26, 171 Translation, 29, 125, 171 Translocation, 92, 171 Transmitter, 123, 127, 136, 148, 156, 171 Trauma, 155, 164, 171 Tricuspid Atresia, 134, 171 Tryptophan, 132, 171 Tumorigenic, 22, 171 Tyrosine, 84, 85, 136, 171 U Ulcer, 153, 171 Ultrasonography, 23, 171 Unresectable, 72, 172 Urethra, 162, 172 Urinary, 172, 173 Urine, 17, 128, 172 Urogenital, 26, 172 Uterine Contraction, 123, 172 V Vaccines, 172, 173 Vagina, 26, 131, 146, 152, 172 Vaginal, 32, 33, 34, 38, 43, 44, 48, 50, 53, 54, 60, 64, 69, 74, 98, 172 Vascular, 9, 74, 128, 138, 147, 155, 159, 160, 161, 172 Vascular Resistance, 128, 172 Vasodilator, 129, 137, 172 Vector, 7, 12, 24, 171, 172 Vein, 148, 156, 172 Venous, 162, 171, 172 Ventricle, 127, 134, 146, 163, 170, 171, 172 Ventricular, 134, 171, 172 Venules, 129, 172 Vesicular, 143, 153, 172

185

Veterinary Medicine, 107, 172 Viral, 13, 24, 92, 157, 163, 171, 172 Viral Load, 13, 172 Virilism, 145, 172 Virulence, 170, 172 Virus, 92, 127, 138, 148, 159, 165, 171, 172, 173 Visceral, 127, 149, 159, 173 Visceral Afferents, 127, 173 Vitro, 5, 7, 20, 26, 173 Vivo, 5, 7, 8, 10, 20, 26, 28, 151, 173 Voltage-gated, 25, 173 W White blood cell, 126, 147, 149, 150, 151, 154, 159, 173

Windpipe, 170, 173 Womb, 172, 173 Wound Healing, 4, 94, 132, 151, 173 X Xanthine, 83, 173 Xenobiotics, 28, 173 Xenograft, 30, 125, 173 X-ray, 28, 141, 156, 164, 173 Y Yolk Sac, 140, 173 Z Zymogen, 162, 173

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Mifepristone

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