PROGESTERONE 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., 1960Progesterone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84054-7 1. Progesterone-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on progesterone. 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 PROGESTERONE ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Progesterone.................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 63 The National Library of Medicine: PubMed ................................................................................ 71 CHAPTER 2. NUTRITION AND PROGESTERONE............................................................................. 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Progesterone............................................................................... 115 Federal Resources on Nutrition ................................................................................................. 121 Additional Web Resources ......................................................................................................... 121 CHAPTER 3. ALTERNATIVE MEDICINE AND PROGESTERONE ...................................................... 125 Overview.................................................................................................................................... 125 National Center for Complementary and Alternative Medicine................................................ 125 Additional Web Resources ......................................................................................................... 136 General References ..................................................................................................................... 141 CHAPTER 4. DISSERTATIONS ON PROGESTERONE ........................................................................ 143 Overview.................................................................................................................................... 143 Dissertations on Progesterone ................................................................................................... 143 Keeping Current ........................................................................................................................ 146 CHAPTER 5. CLINICAL TRIALS AND PROGESTERONE ................................................................... 147 Overview.................................................................................................................................... 147 Recent Trials on Progesterone ................................................................................................... 147 Keeping Current on Clinical Trials ........................................................................................... 149 CHAPTER 6. PATENTS ON PROGESTERONE ................................................................................... 151 Overview.................................................................................................................................... 151 Patents on Progesterone............................................................................................................. 151 Patent Applications on Progesterone......................................................................................... 162 Keeping Current ........................................................................................................................ 187 CHAPTER 7. BOOKS ON PROGESTERONE ....................................................................................... 189 Overview.................................................................................................................................... 189 Book Summaries: Online Booksellers......................................................................................... 189 The National Library of Medicine Book Index ........................................................................... 191 Chapters on Progesterone .......................................................................................................... 192 CHAPTER 8. PERIODICALS AND NEWS ON PROGESTERONE ......................................................... 193 Overview.................................................................................................................................... 193 News Services and Press Releases.............................................................................................. 193 Academic Periodicals covering Progesterone ............................................................................. 195 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 197 Overview.................................................................................................................................... 197 U.S. Pharmacopeia..................................................................................................................... 197 Commercial Databases ............................................................................................................... 198 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 203 Overview.................................................................................................................................... 203 NIH Guidelines.......................................................................................................................... 203 NIH Databases........................................................................................................................... 205 Other Commercial Databases..................................................................................................... 207 The Genome Project and Progesterone....................................................................................... 207 APPENDIX B. PATIENT RESOURCES ............................................................................................... 213 Overview.................................................................................................................................... 213
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Patient Guideline Sources.......................................................................................................... 213 Finding Associations.................................................................................................................. 216 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 219 Overview.................................................................................................................................... 219 Preparation................................................................................................................................. 219 Finding a Local Medical Library................................................................................................ 219 Medical Libraries in the U.S. and Canada ................................................................................. 219 ONLINE GLOSSARIES................................................................................................................ 225 Online Dictionary Directories ................................................................................................... 225 PROGESTERONE DICTIONARY.............................................................................................. 227 INDEX .............................................................................................................................................. 315
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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 progesterone 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 progesterone, 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 progesterone, 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 progesterone. 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 progesterone, 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 progesterone. 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 PROGESTERONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on progesterone.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and progesterone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “progesterone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Effects of Progesterone on the Urinary Tract Source: International Urogynecology Journal. 4(4): 232-236. 1993. Summary: The effects of progesterone on the urinary tract are not thoroughly discussed in the literature except with respect to hydronephrosis of pregnancy. This article is a comprehensive review of the effects of progestational agents on the ureter, bladder and urethra and the possible clinical uses of this hormone. The authors conclude that, from the data in the literature, it appears that progesterone brings about relaxation of smooth muscle in the urinary system. These findings may be important clinically in managing menopausal women on hormone replacement as well as younger women using oral contraception. 1 figure. 43 references. (AA).
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Federally Funded Research on Progesterone The U.S. Government supports a variety of research studies relating to progesterone. 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 progesterone. 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 progesterone. The following is typical of the type of information found when searching the CRISP database for progesterone: •
Project Title: A PR-INDUCED AUTOCRINE/PARACRINE PATHWAY IN FEMALE BRAIN Principal Investigator & Institution: Apostolakis, Ede M.; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 12-APR-2002; Project End 31-MAR-2005 Summary: Ovarian steroid hormones, estrogen (E) and progesterone (P), exert profound influence on development, reproduction, and aging through activation of cognate nuclear receptors (ERa, PR isoforms a and b). In addition to synthesis of PR in female hypothalamic ventromedial nucleus (VMN), E induces changes in local microcircuitry, an effect that requires cAMP activity and for receptivity. Since cAMP increases synthesis and release of constitutive pituitary adenylyl cyclase-activating polypeptide (PACAP) in other tissue for local binding to PACAP receptors, the goal of this proposal is to determine whether E-induced PACAP mediates a novel autocrine/paracrine transsynaptic loop within VMN microcircuitry required for onset of P-facilitated receptivity. Since studies on the biological role of PR have been hampered by a lack of knowledge of the cell-lineages that express PR isoforms, mice with selective ablation of PRa (PRAKO) and PRb (PRBKO) will be studied. The specific aims of this project are: 1) To determine whether E and P and their cognate receptors [ERa, PRa, PRb] regulate the synthesis and release of pituitary adenylyl cyclase-activating polypeptide (PACAP) in the microcircuitry of the VMN ultimately for receptivity, 2) To characterize the gene expression profile ('molecular fingerprints') of individual PR-expressing and adjacent nonPR- expressing cells in the VMN that mediate isoform-specific PR- facilitated behavior, 3) To identify the steroid-induced mechanism(s) and its major components (VMN expression pattern of membrane-bound receptors [PAC1, VPAC, VPAC2]; signaling pathway [cAMP, MAPK] by which PACAP mediates isoform-specific PRfacilitated behavior. Well-established procedures [in situ hybridization, blot analysis, immunohistochemistry, steroid receptor-dependent behavioral] and new technologies [real-time RT-PCR, single cell expression profiling (molecular fingerprinting), microarrays, Laser capture of individual cells] will be used. By monitoring coordinate
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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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changes in PACAP activity, intracellular signaling, and gene expression induced specific steroid receptors (PRa and PRb) in the individual VMN cells that correlate with hormone status and behavior, unique insight into the biological consequences of expressed genetic variability of cells will be identified. This will furnish insight into the underlying cellular and molecular mechanisms that produce steroid receptor-dependent disease etiologies and should contribute to the development of new therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE, GENDER, SEROTONIN AND RESPIRATORY CONTROL Principal Investigator & Institution: Behan, Mary; Professor; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Serotonin (5HT) plays a major role in breathing and the control of upper airway function. The proposed research will test the hypothesis that, with increasing age, there is a gender- specific decrease in serotonergic modulation of respiratory motoneurons. Because of gender-related differences, aging males may be uniquely susceptible to breathing disorders such as obstructive sleep apnea. Our preliminary data indicate that 5HT immunoreactivity in the hypoglossal nucleus decreases with age in male rats, but increases with age in female rats. Furthermore, long term facilitation, a 5HT-dependent increase in respiratory motor output following intermittent hypoxia, decreases to older male rats, but increases to older female rats. This is the first description of age-associated change in serotonergic modulation of respiratory control, and the first description of sexual dimorphism in age-related changes in any aspect of the serotonergic nervous system. The proposed research will test the hypothesis that gonadal hormones have a neuroprotective role in the maintenance of serotonergic modulation of respiratory motoneurons in female rats with increasing age, and can potentially reverse or delay the age-associated changes that occur in male rats. Five specific aims are proposed, each corresponding to a testable hypothesis. First, we will use neurochemical and anatomical assays to detect age- and gender- related changes in key elements of the serotonergic neuromodulatory system (5HT, 5HT receptors, and the serotonin reuptake transport protein) in hypoglossal and phrenic motor nuclei. Secondly, we propose to determine if there are functional consequences of aging and gender on respiratory responses to hypoxia in awake rats. Thirdly, we will test the hypothesis that serotonin-dependent components of the hypoxic ventilatory response are decreased selectively with aging in male rats. Finally, we propose to investigate the influence of neutering and hormone replacement therapy (estrogen, progesterone, testosterone) on our anatomical and physiological indices of serotonergic modulation of respiration in male and female rats. To our knowledge, this is the first proposal to study age and gender effects on any form of plasticity in respiratory control. An understanding of these mechanisms may lead to therapeutic strategies for intervention in age-related breathing disorders that affect both men and women such as obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASSEMBLY MECHANISMS FOR STEROID RECEPTOR COMPLEXES Principal Investigator & Institution: Smith, David F.; Associate Professor; Mayo Clinic Arizona Sc Johnson Research Medical Building Scottsdale, Az 85259 Timing: Fiscal Year 2001; Project Start 01-JUL-1992; Project End 31-JUL-2003
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Summary: The overriding goal of this proposal is to understand the role of molecular chaperones in regulating the function of steroid receptors. The Specific Aims of this proposal seek to define the mechanisms responsible for ordered, dynamic chaperone interactions with steroid receptors. Key to these ordered interactions are partner proteins-Hip, Hop, and BAG1 - for the major nucleocytoplasmic chaperones Hsp70 and Hsp90. Aim 1. Obtain three-dimensional structures for Hip and Hop, either alone or in co-crystals with Hsp70 or Hsp90. Aim 2. Test the hypothesis that the DP-repeat motifs appearing near the C-termini of both Hip and Hop play a major role in directing assembly progression of progesterone receptor complexes. The putative DP interaction sites on Hip and/or Hop will be defined by biochemical and molecular approaches. Next, mutant proteins will be generated to test the functional importance of these sites. Aim 3. Test the hypothesis that the Hsp70 partner BAG-1 is required for efficient assembly and hormone-dependent activation of PR complexes. Three different BAG1 isoforms will be compared for their abilities to participate during specific stages of progesterone receptor assembly, and participating isoforms will be tested for functional involvement in maintaining the dynamics of receptor-chaperone interactions and in promoting hormone-dependent dissociation of receptor complexes. Achieving these aims will provide a better basic understanding of the interplay between components of the molecular chaperone machinery. The knowledge gained from the steroid receptor model will also provide a paradigm for a variety of other signaling proteins whose activities are regulated by a similar chaperone pathway. One potential consequence of these studies is the development of novel therapeutic approaches to the treatment of steroid-dependent diseases and the modulation of normal steroid-mediated processes. However, since the pathway of chaperone interactions that underlies the maturation and maintenance of steroid receptors also occurs with proteins in other signal transduction pathways, there are many additional potential applications of these basic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASTROCYTE-NEURON INTERACTIONS AND GNRH NEURONAL FUNCTION Principal Investigator & Institution: Brann, Darrell W.; Associate Professor; Phys Med and Rehabilitation; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2006 Summary: (Scanned from the applicant's description): Estrogen is well known to play a critical role in reproduction and to have important beneficial effects on the brain. The mechanism(s) underlying these important effects of estrogen are unknown and represent the focus of this grant application. Our major hypothesis is that astrocytes function to mediate, at least in part, the reproductive and beneficial effects of estrogen on the brain. Thus, we propose that astrocytes are capable of regulating the neurosecretion, neuronal connectivity and survival of GnRH and non-GnRH neurons and that these effects are primarily due to the ability of astrocytes to release transforming growth factor-beta (TGFbeta). Central to this proposed mechanism, is the hypothesis that 17beta-estradiol exerts regulatory control over astrocytes to stimulate release of TGFbeta. This putative 17beta-estradiol-astrocyte-TGF-beta signaling pathway could have important implications not only to reproduction, but could also provide a conceptual framework to explain how estrogen may be beneficial in certain clinical situations such as stroke and Alzheimer's disease. Aim 1 would establish whether TGFbeta mediates the GnRH-releasing, neurite outgrowth and neuroprotective actions of hypothalamic astrocytes. This aim would characterize the different TGF-beta isoforms
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released by hypothalamic astrocytes, the degree of correlation between their levels and the functional effects of hypothalamic astrocyte-conditioned media (HA-CM), and perform causative studies to prove a role for TGFbeta. Aim 2 would characterize the recently discovered 17beta-estradiol-astrocyte-TGFbeta signaling pathway in the hypothalamus and establish the underlying mechanisms and functional implications of the pathway. This aim would determine the specific TGFbeta isoforms regulated by 17beta-estradiol, the functional importance of such regulation, whether it is ERalpha or ERbeta that mediates the 17beta-estradiol effects, and the applicability of the novel pathway to other clinically important estrogen target tissues, such as cortex and hippocampus, as well as to the human. Aim 3 will establish whether steroid hormones upregulate TGFbeta type I, II and/or III receptors in GnRH neurons during the time of the LH surge. Preliminary results showed a dramatic up-regulation of the TGFbeta type II receptor in the hypothalamus at the time of the LH surge induced by estrogen plus progesterone. This aim would confirm these preliminary observations and extend them by determining whether the up-regulation occurs in GnRH neurons, whether it is 17beta-estradiol or progesterone which is responsible for the effect, and determine if the steroid regulation extends to the type I and type III TGFbeta receptors as well. Aim 4 will establish the cell signaling mechanism utilized by HA-CM and TGFbeta to promote neurite outgrowth and exert neuroprotection on GnRH neurons. This study would examine the Ras-Raf-ERK pathway, with the hypothesis that this signaling pathway activates downstream mediators such as the neurite-outgrowth promoting factor, growth associated protein-43 (GAP-43), and the anti-apoptotic proteins bcl-2 and bcl-xl in order to promote neurite-outgrowth and survival of GnRH and non-GnRH neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN OXYTOCIN RECEPTORS--FUNCTION AND STRUCTURE Principal Investigator & Institution: Flanagan-Cato, Loretta M.; Psychology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2001 Summary: (Adapted from applicant's abstract): This is a revised application for a FIRST award (R29). My long-term research goal is to establish an independent multidisciplinary research program to reveal the mechanisms whereby ovarian steroid hormones regulate female sexual behavior in rats. This behavior has long served as an excellent model system for the biological basis of steroid hormone actions in brain. Previous studies have shown that oxytocin receptors (OTRs) in the hypothalamus facilitate female sexual behavior after pretreatment with estradiol and progesterone. Estradiol appears important for enhancing the level of mRNA for this protein. In the absence of progesterone, however, these estradiol-induced receptors are not sufficient for OT to augment sexual behavior. The mechanism of progesterone's permissive effects are not known. The proposed experiments will examine the mechanisms of estradiol and progesterone regulation of OTR expression and function in the rat brain. The first specific aim is to clone OTRs from rat brain. This is expected to enable the investigators to develop the appropriate reagents (e.g., probes, antisera) for subsequent studies. The second specific aim is to test the hypothesis that estradiol and progesterone regulate OTR transcripts by modulating the rate of transcription. This study will not only determine the mechanism for estradiol-induced increases in OTR mRNA, but will also determine whether progesterone actively co-regulates estradiol's effects on OTR transcription. The third specific aim will test the hypothesis that steroid hormoneinduced changes in OTR binding activity in the hypothalamus are associated with alteration in second messenger production. For example, the hypothesis will be tested
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that the biological basis for progesterone-dependent facilitation of sexual behavior by OT is the augmentation of OTR signal transduction. A final inquiry will determine whether any increases in OTR signal transduction are mediated in part by steroid hormone-induced upregulation of G proteins associated with OTRs. Taken together, the proposed experiments will provide a detailed analysis of the multiple levels of regulation by steroid hormones of this neuropeptide receptor to permit plasticity of this biologically important behavior. Insights gained from these studies may be relevant to other examples of steroid interactions with neural circuits, such as stress responses and mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CABLES ROLE IN ENDOMETRIAL DIFFERENTIATION AND CANCER Principal Investigator & Institution: Rueda, Bo R.; Assistant Professor/Senior Scientist; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Endometrial cancer (EC) is the most common gynecologic malignancy in the United States and is believed in most cases to be related to overexposure to unopposed estrogens. EC is usually curable with surgery. Alternatively, progesterone, a natural inhibitor of cellular proliferation of the endometrium, has been used with limited success for endometrial hyperplasia or EC in patients who are concerned about fertility. The mechanisms of progesterone action, however, have yet to be defined. Progesterone can influence regulatory components of the cell cycle (e.g. cyclins, cyclin dependent kinases; cdks). Our recent studies have demonstrated that Cables, a novel cell cycle regulatory protein, is lost at a high frequency in EC. Cables appears to act as a linker protein, which facilitates tyrosine 15 phosphorytation of some cdks by non-receptor tyrosine kinases. Cdk2 regulates the G1 S-phase transition of the cell cycle and cdk2 tyrosine phosphorylation is inhibitory and leads to decreased cdk2 activity and slows cell growth. Cables enhances this inhibitory phosphorylation, so loss of Cables should result in increased, and possibly uncontrolled, cell growth. Progesterone appears to transcriptionally regulate Cables in epithelial cells derived from proliferating endometrium, but not in EC cell lines. More interesting, the Cables deficient mice have evidence of endometrial hyperplasia at 3 months of age and as such appears to be a mouse model that mimics the human disease. Collectively, these data have led us to hypothesize that Cables expression in normal endometrial epithelium is hormonally regulated, and Cables is absent or tess effective in transformed/transforming cells. Furthermore, we believe that a loss, or a reduced level of, Cables leads to atypical endometrial hyperptasia and/or neoplasia. To test our hypotheses, we have proposed the following aims 1) Determine the role of progesterone in mediating Cables induced inhibition of endometrial cell proliferation in vitro, 2) Determine if Cables is required for the anti-proliferative effects of progesterone in endometrial cells, and if loss of Cables facilitates EC development in vivo, 3) Investigate the endometrial changes associated with proliferation and differentiation during the estrous cycle and abnormal endometrial growth in Cables deficient mice, 4) Determine the mechanism of Cables gene inactivation in primary :human EC. The studies in this proposal will help determine the: role of Cables in I normal and malignant endometrial epithelium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR AND MOLECULAR MECHANISMS OF MAMMALIAN OVULATION Principal Investigator & Institution: Park-Sarge, Ok-Kyong K.; Associate Professor; Physiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The long-term goal of our research is to elucidate the molecular cascades of LH-induced signals within preovulatory follicles, leading to ovulation. The LH surge stimulates the synthesis of progesterone and its intracellular receptors, progesterone receptors (PRs), in the granulosa cells of preovulatory follicles. Interaction between progesterone and PRs in an autocrine/paracrine fashion is essential for ovulation. However, the exact mechanisms by which ligand-dependent activation of PRs controls ovulation and thus normal reproductive cyclicity and fecundity are unknown. To gain insight into the molecular mechanisms underlying PR-mediated ovarian functions, we initiated cloning of PR downstream genes in luteinizing granulosa cells. The two genes we have characterized as PR-downstream are the ligand-receptor system for pituitary adenylate cyclase activating polypeptide (PACAP): PACAP and its receptor type 1 (PAC1). The temporal and spatial pattern of expression and secretion of the ligand PACAP along with the cellular localization of the receptor PAC1 in the ovary advocates the potential significance of this ligand-receptor system for ovulatory processes. Indeed, pharmacological blockade of ligand-dependent activation of PAC1 appears to interfere with the efficacy of LH and progesterone in bringing about ovulatory processes. Thus, our working hypothesis is that PACAP-induced activation of PAC1 mediates, at least in part, PR function critical for follicular rupture with release of a meiotically mature oocyte. The immediate goal of this application is to determine the functional importance of PACAP within preovulatory follicles during the periovulatory period, using in vivo and in vitro approaches. In Aim 1, we will test whether PRinduced PACAP is critical for follicular rupture and for expression of ovulation-related genes, including proteolytic enzymes. In addition, we will identify PAC1-downstream genes that may play an important role in follicular rupture. In Aim 2, we will determine the initial death/survival pathway(s) that is modulated by PR-induced PACAP in luteinizing granulosa cells. In Aim 3, we will test whether PR-induced PACAP regulates the polyadenylation/translation capacity of meiotically maturing oocytes. The proposed studies are designed to provide functional endpoint(s) of interaction between PRinduced PACAP and PAC1 in preovulatory follicles during the periovulatory period. Information derived from our results will allow us to better manage fertility, infertility, and endocrine-based disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COCAINE & STEROIDS: BRAIN VASCULAR & BEHAVIORAL EFFECTS Principal Investigator & Institution: Kaufman, Marc J.; Assistant Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Chronic cocaine use causes brain abnormalities and cognitive dysfunction, which may both impair a drug user's ability to resist further drug use and decrease the efficacy of treatment interventions. The severity of cocaine associated brain dysfunction is less in women than in men. Further, cocaine abuse treatment appears to benefit women more than men. These sex differences have important therapeutic implications, because they suggest a protective role for estrogen.
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Progesterone
Thus, estrogen (or a related compound) might be of therapeutic use to protect against brain vascular dysfunction. Cocaine's ability to reduce cerebral blood flow is likely to play a critical role in the development of brain dysfunction. Estrogen has been shown to acutely improve, while progesterone and testosterone acutely degrade vascular function. Consequently, vascular effects of hormones may account for sex differences in cocaine's brain effects. We seek to determine whether estrogen, progesterone, and testosterone alter cocaine pharmacokinetics and cocaine's acute cerebral vasoconstrictive effects. We will measure cocaine and hormone pharmacokinetics, and characterize cardiovascular responses after combined intravenous cocaine (0.4 mg/kg) and estrogen (men), or progesterone or testosterone (women) treatments. Subsequently, we will evaluate whether these hormones alter cocaine's acute cerebrovascular effects, using a noninvasive functional MRI technique called Dynamic Susceptibility Contrast MRI (DSC MRI). DSC MRI measures cerebral blood volume (CBV) and blood flow (CBF). Study subjects will include healthy men and women with histories of occasional cocaine use, who will each participate in a randomized, placebo-controlled, double-blind study. The pharmaceutical industry is actively developing novel steroid receptor agents with greater receptor selectivity than the natural hormones, which may improve the ability to selectively modulate vascular responses to cocaine. Thus, if our hypotheses regarding hormonal effects on cocaine-induced vasoconstriction are validated, the potential for identifying effective therapeutics for investigation in chronic treatment trials will be enhanced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF CORTICOTROPIN DURING PREGNANCY Principal Investigator & Institution: Keller-Wood, Maureen Pharmacodynamics; University of Florida Gainesville, Fl 32611
E.;
Professor;
Timing: Fiscal Year 2003; Project Start 01-JUL-1987; Project End 31-JAN-2007 Summary: (provided by applicant): The overall objective of the proposed research is to determine the mechanism for increased ACTH secretion during pregnancy. This increase is necessary for normal maternal and fetal homeostasis, and occurs without symptoms associated with increased steroid action, such as hypertension. We have hypothesized that action of corticosteroids at mineralocorticoid receptors (MR) leads to reduced MR action in pregnancy, and that progesterone mediates this effect as a competitive antagonist at MR. The studies done thus far have supported this hypothesis, showing changes in hippocampal MR consistent with reduced activation and the presence of antagonist activity, during progesterone treatment or pregnancy. The proposed studies will extend these studies to test the following hypotheses: 1) Progesterone treatment in vivo blocks MR effects on 5HT1A expression in hippocampal neurons, resulting in increased plasma ACTH levels. The magnitude of the effects on both 5HT1A expression and ACTH is related to the levels of cortisol relative to progesterone. 2) Progesterone treatment in vivo has selective effects on neurons in hippocampal regions expressing mineralocorticoid receptors (MR) but not progesterone receptors (PR) (including CA1 and dentate gyrus). 3) The increase in ACTH caused by pregnancy or progesterone treatment is caused by an increase in serotonin effects in the brain; 4) The interaction between cortisol and progesterone in hippocampal cells in vitro involves competition at MR, producing opposing effects on 5HT1A mRNA and on the hyperpolarization response to 5HT (serotonin); and 5) Progesterone inhibits activation of MR, resulting in reduced MR binding to specific response elements, including those in the 5HT1A promoter. The first 3 aims will be studied in experiments in sheep. The sheep will be studied either after chronic progesterone treatment, ovariectomy or
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during pregnancy; MR binding and 5HT1A mRNA, as well as MR, GR and PR mRNA will be measured in hippocampus, hypothalamus and medulla. To test whether changes in 5HT1A occur in the same types of cells in hippocmapus as express MR (but not PR), mRNA will also be determined by in situ hybridization. To test the role of 5HT1A during pregnancy, the ability of a 5HT1A agonist to inhibit the ACTH levels in pregnancy and in progesterone-treated ewes will also be determined. The final 2 aims will be tested in cultures of hippocampal neurons. The effect of progesterone on MR binding, 5HT1A mRNA and electrical responses to a 5HT agonst will be tested; single cell PCR will also be used to determine if cells contain MR, but not PR. The action of progesterone at MR will also be tested by using MR-selective antagonist and agonist, and GR-PR antagonist. Finally, the ability of progesterone to inhibit MR activation will be tested in gel-shift and super-shift assays using specific response elements in the 5HT1A promoter, including a nGRE and the SP-1 site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECIDUAL SIGNALS IN THE ESTABLISHMENT OF PREGNANCY Principal Investigator & Institution: Soares, Michael J.; Professor; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The establishment and maintenance of pregnancy require the appropriate development of a specialized maternal tissue, referred to as decidua. Decidual cells arise from uterine stroma via the actions of progesterone, form intimate relationships with placental structures, and facilitate the development of the embryo. Among the important functions of decidual cells are their hormone/cytokine producing capabilities. Hormone/cytokines related to prolactin (PRL) are prominent decidual cell secretory proteins and include, decidual/trophoblast prolactin-related protein (d/tPRP). The uteroplacental PRL family contributes to the regulation of uterine inflammatory cell responses accompanying pregnancy. D/tPRP has been shown to associate with heparin containing molecules in the extracellular matrix and specifically interact with eosinophils. Eosinophils are a part of the maternal inflammatory response and must be controlled in order to ensure the establishment of pregnancy. We hypothesize that the decidual cell product, d/tPRP, participate in the modulation of maternal adaptations to pregnancy, including mediation of the anti-inflammatory actions of progesterone. In this research project, we propose to investigate decidual cell signaling. In Aim 1 we propose to identify cellular responses to d/tPRP. Aim 2 focuses on determining mechanisms underlying the interactions of d/tPRP with heparin and eosinophils. Under Aim 3 we examine d/tPRP- eosinophil interaction in vivo. The planned research utilizes cellular and molecular and in vitro and in vivo strategies. Data derived from the proposed experimentation will improve our understanding of the nature of decidua cell signaling and the role of the decidual PRL family in the regulation of viviparity. These findings will provide considerable insight into the etiology of developmental disorders associated with pregnancy failure and will also have important ramification on our understanding of the control of eosinophil functions in aberrant processes such as immune disease and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF SMOKED HEROIN ACROSS THE MENSTRUAL CYCLE Principal Investigator & Institution: Evans, Suzette M.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032
12
Progesterone
Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): There is growing evidence that there are sex differences in response to drugs of abuse. However, only a limited number of studies in rodents have assessed whether there are sex differences in the reinforcing effects of opioids and the human data are sparse. Nevertheless, some of the sex differences observed can be attributed to cycling ovarian hormones in females. This proposal will parametrically evaluate the behavioral and reinforcing effects of smoked heroin across the menstrual cycle in normally-cycling adult female rhesus monkeys, Levels of estradiol (EST), progesterone (PRO) and luteinizing hormone (LH) will be routinely monitored, correlating changes in hormone levels to the behavioral effects of heroin. Exp. 1 will carefully characterize the time course of heroin blood levels across the menstrual cycle. Subsequently, heroin seeking and taking will be measured using a second-order schedule, choice and location preference procedures when the monkeys are not dependent (Exp. 2) and again (Exp. 4) when they are dependent on opioids; and the reinforcing effects of heroin will be measured using a Progressive Ratio procedure when the monkeys are not dependent (Exp. 3) and again (Exp.5) when they are dependent on opioids. These experiments will provide valuable data about changes in the behavioral and reinforcing effects of heroin across the menstrual cycle when heroin is available under non-dependent and dependent conditions. In addition, this proposal will provide important information on the effects of self-administered opioids on the regulation of the menstrual cycle. The proposed studies will be the first to systematically evaluate these effects in female non-human primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARTURITION
ENDOCRINE
AND
PARACRINE
RELATIONSHIPS
IN
Principal Investigator & Institution: Novy, Miles J.; Head; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-JAN-1979; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): The objectives of this research plan are to clarify the relationships among endocrine, paracrine, and cellular events which culminate in parturition in primates. Aim 1 will establish the separate effects of exogenous ACTH or CRH administered to the fetus or mother at 80+ percent gestation in terms of inducing premature labor as well as describe the changes in the endogenous levels of the same hormones. Aim 2 will describe the presence of androgen and glucocorticoid receptors (ARs, GRs) in rhesus amnion, chorion, decidua, and myometrium at 80 and 100 percent of gestation using immunohistochemistry and ribonuclease protection assay of receptor mRNA. A second part of Aim 2 will use maternal/fetal infusion of androgen agonists and antagonists and a 5-alpha reductase inhibitor to determine the effects of alterations of maternal/fetal androgen levels on gestational length. Aim 3 examines possible mechanisms of progesterone withdrawal by testing for a switch between myometrial progesterone receptor (PR) subtypes (A&B) near term, or a non-genomic mechanism of reduced amniochorion calcium mobilization ("membrane effects") in immune cells. Aim 4 will determine the effects of intraamniotic administration of human IL-8 on parturition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENDOCRINE REGULATION OF MATERNAL BEHAVIOR Principal Investigator & Institution: Bridges, Robert S.; Professor of Biomedical Sciences; Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 01-SEP-1990; Project End 31-MAY-2005 Summary: The long-term goal of this project is to identify the neural and neurochemical mechanisms underlying the regulation of maternal behavior and to elucidate potentially novel mechanisms of neural plasticity associated with the expression of maternal behavior in the adult mammal. The specific hypothesis that will be tested is that the induction, maintenance, and retention of maternal care are under endocrine regulation by a neural lactogenic system, a system that displays significant plasticity as a function of reproductive experience. The first series of studies will examine the role of the neural prolactin (PRL) receptor in the initiation of maternal behavior. Using a rat model, we will determine whether placental lactogens, like PRL, act via the PRL receptor to stimulate the onset of behavior. A second study will use the novel PRL receptor antagonist, S 179D-PRL, which will be administered centrally to test the hypothesis that activation of the PRL receptor by lactogenic hormones around the time of birth is essential for the normal onset of maternal care. The third study using ISHH will measure how pregnancy concentrations of progesterone (P) and estradiol affect expression of mRNA for neural PRL receptors. Then, central sites of P action will be examined to see how P affects the onset of maternal care and to delineate a mechanism of P's action in the initiation of maternal behavior. A second series of experiments will determine the involvement of the endocrine system in ongoing maternal care. First, the effects of exposure to PRL-secreting ectopic pituitary grafts on pup-directed maternal care and maternal aggression will be measured. Then, the effects of central administration of the PRL receptor antagonist, S179D- PRL, will be examined in lactating rats. The third set of experiments will delineate the role of the endocrine system in the retention of maternal behavior: The involvement of PRL in the opioidmediated establishment of the retention of maternal behavior will be assessed. Finally, the effects of prior maternal experience on activation of the neural lactogenic system will be measured to see whether prior maternal experience up-regulates the brain PRL system and makes the female more sensitive to her own neural hormones. The results of these investigations will delineate common endocrine and neurochemical regulators of maternal care in mammals, present a new model for examining neuroplasticity in the adult female, and provide a basis for evaluating the effects of endocrine and neurochemical imbalances on mother-young interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENDOMETRIUM DECIDUALIZATION
GENE
REGULATION
DURING
Principal Investigator & Institution: Tseng, Linda; Professor; Ob, Gyn, and Reproductive Med; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 30-SEP-1985; Project End 31-JAN-2004 Summary: The long-term goal of this study is to determine the function of transcription factors expressed during endometrial cell decidualization. We hypothesize that a handful of transcription factors regulate the downstream target gene activation to develop deciduoma receptive to the embryo and to maintain diversified biological functions during pregnancy. To pursue the proposed study, human endometrial cell culture which recapitulates the process of decidualization in vivo has been established. Using this system we have elucidated the progestin-induced production of insulin-like
14
Progesterone
growth factor binding protein-1 (IGFBP-1), the major secretory protein of decidual cells. We have also identified the essential cis-elements in the promoter of the, IGFBP-1 gene. These cis-elements provide molecular tool to analyze the functions of decidual cell transcription factors. The proposed study has four specific aims: Aim 1 will identify and characterize the transcription factors that regulate the activation of the IGFBP-1 gene. The study will focus on the modes of action of the binding proteins of C/TCAAT, CRE , Sp1 and GATA motifs and progesterone receptor (PR) of PRE motif. Aim 2 will determine the functions of the transcription factors, described in aim 1, in the promoters of prolactin (PRL), PR, and fibronectin (FN) in stromal/decidual. Aim 3 will determine how these transcription factors act on the endogenous gene, IGFBP-1, PRL, PR and FN. Aim 4 will determine the effects of estrogen, progesterone and synthetic steroids, agonists/antagonists on the mRNA levels of the functional transcription factors. Results obtained from the proposed study will help us to understand how the transcription factors control the process of decidualization in the human endometrial stromal/decidual cells. This information can be applied to improving the fertility regulation, tissue-specific fertility control, treatment of implantation failure and pregnancy disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN EFFECTS ON CHOLINERGIC FUNCTION IN OLDER WOMEN Principal Investigator & Institution: Newhouse, Paul A.; Professor; Psychiatry; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The primary goal of this proposal is to examine in detail the effects of estrogen, estrogen antagonists, and progesterone on cognitive functions that are affected by cholinergic systems of the brain in postmenopausal women. These systems have critical relevance for the development of age-related cognitive and behavioral changes as well as the symptoms of dementing disorders such as Alzheimer's disease. Changes in estrogen levels after surgical and natural menopause are associated with negative changes in cognitive and behavioral functioning, which are preventable by estrogen administration. Administration of estrogen after menopause is associated with a lower risk of Alzheimer's disease. Specifically, these studies will examine the effects of estrogen and related gonadal steroids on the cholinergic system of the human brain that is thought to be critical for attention, learning, memory, and psychomotor performance. These studies will utilize a well-established method for probing the integrity of central cholinergic mechanisms utilizing cholinergic (muscarinic and nicotinic) antagonists. Preliminary data suggest that short-term administration of estrogen partially protects women from the negative cognitive effects of cholinergic antagonists. This effect could be mediated by trophic effects of estrogen on central cholinergic neurons. Estrogen has a substantial effect on the expression and activity of trophic factors such as Nerve Growth Factor (NGF) and its receptors, thereby directly producing neuroprotective and trophic effects. Estrogen also appears to have signaltransduction modulating properties. These effects are observed particularly in cholinergic neurons of the basal forebrain. However, women are now often taking agents, which may antagonize or modify estrogen effects such as the gonadal steroid progesterone and the anti-estrogen tamoxifen. Studies in this proposal will examine the acute vs. chronic effects of estrogen on anti-cholinergic induced cognitive changes, effects of combined estrogen-progesterone treatment on cholinergic integrity, and the effects of the estrogen antagonist tamoxifen on the cholinergic system. These studies will
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provide knowledge regarding the magnitude and type of effects of estrogen on cholinergic system integrity and will contribute to an understanding of the potential use of estrogen in late life for maintenance of cognitive functioning during normal aging and the prevention and/or treatment of age-related cognitive disorders such as mild cognitive impairment and Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN, HPV, AND CERVIX CANCER IN TRANSGENIC MICE Principal Investigator & Institution: Arbeit, Jeffrey M.; Associate Professor of Surgery; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAR-2003 Summary: (adapted from the investigator's abstract) "High risk" human papillomaviruses (HPV's). such as HPV type 16, are associated with over 80% of cervical cancers. HPV16 expression alone is insufficient to induce carcinogenesis, which requires specific co-factors. We have developed an animal model in which one co-factor associated with HPV neoplasia, chronic estrogen treatment, induces multi-step cervical and vaginal carcinogenesis in transgenic mice expressing the entire early region of HPV16 under control of the human keratin-14 promoter (K14-HPV16 transgenic mice). We will investigate the hypothesis that the cooperation between estrogens and the oncogenes of HPV is a major determinant of cervical carcinogenesis. The specific aims are: 1. Examine whether cervical neoplasia is decreased by decreasing doses of estrogen or by the addition of progesterone, and determine whether carcinogenesis persist after the cessation of estrogen treatment. 1.1. Determine a threshold dose of estrogen for cervical carcinogenesis. 1.2. Investigate growth of cervical neoplastic lesions or carcinoma independent of exogenous estrogen. 1.3. Investigate alteration of estrogen induced cervical carcinogenesis by progesterone. 2. Investigate the functional role of estrogen receptor in estrogen induced cervical carcinogenesis in K14-HPV16 transgenic mice. 2.1. Examine the level of expression of the estrogen receptor, and an estrogen inducible gene containing an estrogen response element, during cervical carcinogenesis. 2.2.1 Test the contribution of estrogen receptor signaling to cervical carcinogenesis by creating and treating composite 14K-HPV16/estrogen receptor knockout (ERKO) with estrogen. 2.2.2. Investigate the effect of pharmacological inhibition of estrogen receptor on estrogen induced cervical carcinogenesis. 2.3. Manipulate expression of the estrogen receptor in different target cells of the reproductive tract to examine contributions of both epithelium and stroma to cervical carcinogenesis. 2.3.1. Determine the role of the epithelium and stroma in estrogen induced cervical carcinogenesis by expressing both the estrogen receptor and the HPV oncogenes in squamous epithelium in ERKO mice lacking receptor function in the stroma. 3. Examine the mechanisms of cooperation between HPV oncogenes and estrogen during cervical carcinogenesis. 3.1. Create transgenic mice with 14K-HPV16 constructs containing mutations in the HPV16 E6, E7, or E5 oncogenes, and investigate of each of the HPV oncoproteins to estrogen induced cervical carcinogenesis. Elucidation of synergism between estrogen and HPV may lead to new insights into the role of sex hormones in the genesis and progression of cervical cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Progesterone
•
Project Title: FAMILIAL TRANSMISSION OF EATING PATHOLOGY & SEX HORMONES Principal Investigator & Institution: Klump, Kelly L.; Assistant Professor; Psychology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Anorexia and bulimia nervosa are often chronic disorders with some of the highest mortality rates (.10%) of any psychiatric illness. Greater understanding of the etiology of disordered eating attitudes and behaviors that underlie these sometimes fatal disorders will inform intervention and prevention efforts aimed at their amelioration. The primary purpose of the proposed study is to examine the etiology significance of ovarian hormones in the development of eating attitudes and behaviors by examining phenotypic and genetic relationships between eating pathology and basal estrogen and progesterone levels in a community-based sample of twins. A secondary aim is to examine phenotypic and genetic relationships between the stress hormone cortisol and disordered eating variables. Estrogen is expected to show positive relationships with dietary restraint, weight preoccupation, and eating/weight./body concerns, and negative associations with binge eating and compensatory behaviors. Progesterone is expected to attenuate these relationships, such that lower estrogen: progesterone ratios will be associated with increased binge eating and compensatory behaviors, and decreased dietary restraint and associated attitudes. Cortisol is expected to show significant positive relationships with all forms of disordered eating. Common genetic factors are expected to contribute significantly to all of these hormone/disordered eating phenotypic relationships. Participants will include 50 female dizygotic twins recruited from the campus of Michigan State University and surrounding metropolitan areas who will complete self-report questionnaires assessing body dissatisfaction, weight preoccupation, binge eating, compensatory behaviors, eating concerns, and dietary restraint. Early follicular phase salivary hormone concentrations of estradiol, progesterone, and cortisol will be obtained between the hours of 0800 and 0900. Phenotypic associations between eating variables and hormone concentrations will be examined using within-person correlations whereas genetic associations will be examined via cross- twin, cross-trait correlations (i.e., Twin 1,s eating attitudes with Twin 2's hormone levels) and Cholesky Decomposition and model fitting analyses. Understanding the magnitude and nature of genetic associations will increase understanding of the etiology of eating disorders and lead to the potential identification of endogenous risk factors to be explored in genetic and neurobiological research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER DIFFERENCES IN DRUG ABUSE Principal Investigator & Institution: Becker, Jill B.; Professor; Psychology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-MAY-2008 Summary: (provided by applicant): The onset of addiction to cocaine is more rapid in women than in men. Women begin using cocaine earlier, enter treatment at earlier ages, and are taking more cocaine at intake than men. Furthermore, cocaine cues induce more drug craving in female than male addicts. Basic research on the role of sex and ovarian hormones in the neurochemical and behavioral responses to acute and repeated exposure to cocaine is an important next step to enhance our understanding of the processes involved in gender differences in drug abuse. Experiments proposed will test the hypothesis that female rats are more susceptible to the behavioral effects of cocaine
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than are males because of organizational effects of gonadal hormones during development as well as activational effects of estrogen in adulthood. As a first step towards determining if there are organizational effects of gonadal hormones during prenatal development, we will look at whether there are sex differences in adulthood independent of circulating gonadal hormones in behavioral and neurochemical responses to cocaine. We will also investigate whether estrogen in adult females further enhances the induction and persistence of these measures. Finally, we will explore whether treatment can ameliorate these sex differences, experiments will test the hypothesis that progesterone can reverse the effect of estrogen on cocaine selfadministration. There are 5 specific aims which address these hypotheses: 1) To determine if there are sex differences in or hormonal influences on the persistence of behavioral sensitization to cocaine. 2) To determine if in females, estrogen enhances behavioral sensitization by potentiating the cocaine-stimulated increase in dopamine in dialysate from the dorsal striatum and nucleus accumbens acutely and after sensitization to cocaine. 3) To determine the effect of sex and gonadal hormones on reinstatement of cocaine self-administration. 4) To determine the effect of sex and gonadal hormones on acquisition of cocaine self-administration and breaking point after prior sensitization to cocaine. 5) To determine if progesterone can reverse the effects of estrogen on cocaine self-administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC SUSCEPTIBILITY TO ENDOMETRIAL CANCER Principal Investigator & Institution: Devivo, Immaculata; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 16-AUG-1999; Project End 31-MAY-2004 Summary: (Adapted from the Investigator's Abstract): Excess estrogen exposure unopposed by progesterone is associated with increased risk of endometrial cancer. Polymorphisms in genes involved in estrogen metabolism influence the levels of these hormones and may be associated with an altered risk of endometrial cancer. To date no studies of these polymorphisms have been reported in relation to endometrial cancer and little information is available on the relation between these polymorphisms and circulating hormone levels. Endometrial cancer is particularly worth studying because it is the most estrogen responsive tumor and thus modest effects of hormone-metabolizing genes may be more easily detectable. We propose to use the resources of the wellcharacterized cohort, the Nurses' Health Study, to ascertain the common polymorphisms in key hormone-related genes and to assess whether these genotypes are predictive of future endometrial cancer risk, as well as assessing the functional significance of the variant alleles of these genes by correlating these variants with plasma hormone levels. We will identify and characterize polymorphisms within CYP19 and the progesterone receptor, as well as quantify the association of the known polymorphisms CYP17-A2, COMT-MET, UGT-A(TA)7AA with endometrial cancer and test whether these associations are modified by established endometrial cancer risk factors. These studies will be nested in the subcohort of 32,826 women from Nurses' Health Study who gave blood samples in 1989-1990, and thus will be among the few studies able to prospectively examine these issues in a defined cohort with complete ascertainment of incident cases and comprehensive prospective information on other endometrial cancer risk factors. Matching two controls to each case we will have 98% power to detect a relative risk of 2.0 and 80% power to detect a relative risk of 1.75 for a polymorphism with an 8% homozygous mutant genotype prevalence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Progesterone
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Project Title: GENETIC VARIANTS OF HORMONE RECEPTORS IN OVARIAN CANCER Principal Investigator & Institution: Terry, Kathryn L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): Epidemiologic and in vitro data suggest a role for reproductive hormones in ovarian cancer development. The tissue specific effect of these hormones is controlled by the expression of hormone receptors. Normal ovarian epithelium contains both estrogen and progesterone receptors. Animal models and cell lines demonstrate that estrogen increases ovarian epithelial proliferation and induce ovarian tumors, whereas, progesterone inhibits growth and increases apoptosis of the ovarian epithelium. In addition, epidemiologic literature suggests a protective effect for the combination of estrogen and progesterone in oral contraceptives, which are consistently protective. Unopposed estrogen in the form of menopausal therapy appears to increase ovarian caner risk but formulations with estrogen and progesterone have no consistent relationship with ovarian cancer. Our goal is to examine the effect of genetic variation in hormone receptors on the risk of ovarian cancer, using a New England based case-control study. Specifically, this study will test whether common haplotypes of estrogen receptor genes (estrogen receptor alpha and estrogen receptor beta) or the progesterone receptor gene are associated with an increased risk of ovarian cancer. In addition, this study will test whether the association between a functional polymorphism in the progesterone receptor, +331 G/A, increases ovarian cancer risk. Variables such as parity, menopausal status, body mass index, and exogenous hormones affect estrogen and progesterone levels, therefore, interaction with these variables will be considered. Ovarian cancer is particularly deadly due to its asymptomatic progression and poor prognosis at late stages of disease. Advances in prevention and detection may come from a better understanding of the genetic determinants of ovarian cancer, which might inform decisions about lifestyle modifications that could lower risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONAL INFLUENCES ON COGNITION Principal Investigator & Institution: Luine, Victoria N.; Professor; Hunter College 695 Park Ave New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: A variety of studies show that estrogen may promote memory in females, both animal and human with low estrogen levels. Moreover, estrogen may also delay or prevent the onset of Alzheimer's Disease and improve cognition in women with the disease. Using young and aged rats as models, experiments will examine effects of gonadal hormones on memory using a spatial memory task, object recognition. First, the dose- response relationship between estrogen and enhanced memory will be determined. Whether concurrent administration of progesterone with estrogen alters the enhancing effects of estrogen on memory will be tested. Then possible enduring effects of gonadal hormones on memory will be tested, i.e., whether chronic estrogen alone or with progesterone enhances memory months after discontinuation. Effects of these hormone treatments on GABAergic and monoaminergic neurotransmission in brain areas involved in memory function will be measured by neurochemical techniques. Whether alterations in memory occur over the estrus cycle and after chronic ovariectomy will be determined and will show whether hormones exert short term effects or long term, trophic effects. Thus, proposed experiments will characterized
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fundamental relationships between gonadal hormones and memory function. While important for providing basic information concerning hormone actions and the neural bases for hormonal effects on memory, the studies also have significant health implications for aging and Alzheimer's disease. Concurrent estrogen and progesterone therapy is the treatment of choice for post menopausal women, but little is known about the effects of progesterone on memory. In addition, if post-menopausal hormone replacement therapy can delay dementia onset by 5 years, the incidence of dementia has been projected to decreased by 50%. Finally, if only a few years of replacement can be given with the same benefits on memory loss or in developing AD, then the risk of side effects of estrogen can be greatly minimized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
20
Progesterone
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: HORMONE REPLACEMENT THERAPY WITH PROGESTERONE CREAM Principal Investigator & Institution: Hermsmeyer, Kent R.; Dimera, Llc. 2525 Nw Lovejoy St, Ste 401 Portland, or 97210 Timing: Fiscal Year 2000; Project Start 13-AUG-1998; Project End 31-AUG-2004 Summary: The objective of this project is to further develop a new progesterone formulation that is effective for hormone replacement therapy-protecting the coronary arteries against hyperreactivity. Such hyperreactivity results from the deficiency of progesterone after the cessation of ovarian function after menopause during the normal aging process. The anticipated new product will be further studied in monkeys in the catheterization laboratory and in human stress test electrocardiogram and echo cardiology protocols. These studies will determine the effectiveness of progesterone in extending treadmill stress test duration, echocardiographic cardiac wall motion, and lipid biochemical measures of coronary function. We will also explore the possible relationship of changes in blood lipids and platelet function. The new formulation is designed to be accepted sufficiently well by post- menopausal women to encourage compliance among those who initiate hormone replacement therapy-for a duration of decades in many cases. Protection of the cardiovascular system by progesterone can be expected to provide for a significant decrease in the incidence of cardiovascular disease during aging, and improved quality of life in post-menopausal women. The skin cream formulation is well accepted by women, has optimal pharmacokinetics for a once a day treatment, and is hypothesized to reduce cardiovascular risks, including coronary artery disease. Even though the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, the presently available forms of hormone replacement therapy are used by only a fraction of those who would benefit. This leading risk of death and' available measures to minimize that risk are neither well understood nor readily accepted by post-menopausal women. This formulation has the potential to significantly improve that situation and enhance quality of life in post-menopausal women. PROPOSED COMMERCIAL APPLICATIONS: The percutaneous formulation of progesterone will produce a blood level to minimize the risk of cardiovascular disease, and thus may find widespread application in hormone replacement therapy. The number of people who would be potential consumers for the product consists of all postmenopausal women, a rapidly growing number which already exceeds 20 million. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONES ACTION IN ENDOMETRIOSIS Principal Investigator & Institution: Bulun, Serdar E.; Professor; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: The long-term objective of this application is to characterize the common cellular and molecular mechanisms responsible for resistance to progesterone action and impaired estradiol metabolism in endometriotic tissue in contrast to the eutopic
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endometrium. Progesterone induces the expression of 17beta-hydroxysteroid dehydrogenase (HSD) type 2, which catalyzes the conversion of the potent estrogen, estradiol to a less estrogenic steroid, estrone in endometrial epithelial cells. Our recent data are suggestive that stromal progesterone receptors (PR) mediate the stimulatory effect of progesterone on 17beta-HSD type 2 expression in epithelial cells. Our recent data are suggestive that stromal progesterone receptors (PR) mediate the stimulatory effect of progesterone on 17beta-hSD type 2 expression in epithelial cells. Interestingly, we also demonstrated in vivo the absence of 17beta-HSD type 2 expression in epithelial cells of endometriotic tissue in response to progesterone stimulation and interpreted this find as evidence for resistance to progesterone action. We further showed the that PR isoform B, which mediates the transactivating effects of progesterone in general is absent in endometriotic tissue, whereas only the transrepressor type isoform PR- A is present in this tissue. In contrast, both PR-B and PR-A are expressed and regulated by ovarian steroids in the eutopic endometrium. We hypothesize that the lack of PR-B causes resistance to progesterone action and disruption of the paracrine signaling, which mediates 17beta-HSD type 2 induction in epithelial cells. This results in elevated levels of estradiol, a mitogen for endometriotic tissue. Additionally, the absence of PR-B and the unopposed functions of PR- A may inhibit differentiation and apoptosis and enhance proliferation in endometriotic cells. We propose the following specific aims. (1) The cellular and molecular mechanisms responsible for the lack of PR-B expression in endometriotic tissue will be determined. We will determine, in particular, whether aberrations in steroid receptor expression in endometriotic tissue modulate the differential effects of estradiol on PR-A and PR-B expression. (2) Aberrations in epithelial- stromal interactions, which disrupt the progesterone induction of 17betaHSD type 2 expression in endometriotic tissue will be characterized. (3) We will determine whether the lack of PR-B and the unopposed functions of PR-A in endometriotic tissue are responsible for altered differentiation, apoptosis and proliferation in endometriotic tissue. Identification of the molecular mechanisms responsible for progesterone resistance and their functional consequences in endometriotic tissue may lead to novel strategies for treatment of endometriosis such as the development and use of selective progesterone receptor modulators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONES AND BEHAVIORAL DEVELOPMENT Principal Investigator & Institution: Cushing, Bruce S.; Associate Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 02-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's description): The general purpose of this proposal is to examine the behavioral and neurobiological consequences of development exposure to oxytocin (OT). Changes in OT are particularly likely to occur around the time of birth, and the proposed hypothesis is that the consequences of exposure to OT during the neonatal period may be long-lasting, producing functional changes in adulthood. This hypothesis will be examined in the context of female reproductive behaviors, which are particularly sensitive to the effects of OT and steroid hormones and their interactions. Developmental exposure to OT also may affect CNS levels of OT receptors, which could in turn alter sensitivity to OT in adulthood. In addition to behavioral assessments, the investigator proposes using neuroanatomical methods to index, as a function of neonatal manipulations of OT, both OT and OT receptors in adulthood. Developmental exposure to OT may affect adult behavior by influencing steroid sensitivity; this hypothesis will be examined by the measurement of estrogen or
22
Progesterone
progesterone receptors. In addition, the effects of development exposure to OT on arginine vasopressin (AVP) and its receptor (V1a) will be examined; AVP is closely related to OT in both structure and function. Finally, a nonspecific marker of cellular activity (c-Fos) will be used to index the capacity of animals with different developmental histories to respond to adult treatment with estrogen or OT. The behavioral effects of both OT and estrogen can be species specific; for this reason two animal models (prairie voles and rats) have been selected, taking into account the advantages of each for examining the behavioral effects of both OT and steroid hormones and their interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN ENDOMETRIAL NITRIC OXIDE: REGULATION AND FUNCTION Principal Investigator & Institution: Khorram, Omid A.; Associate Visiting Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (Provided by Applicant): Nitric oxide (NO) is a free radical with diverse physiological functions one of which is its smooth muscle relaxant effects. By virtue of this effect NO plays a key role in regulating vascular tone and therefore 1: flow to many organs including the reproductive tract. Recent identification of predominantly endothelial nitric oxide synthese (eNOS) in the human uterus with primary localization to the endometrial glands has raised the possibility that this molecule may have functions other than regulation of blood flow, such as control of endometrial glandular secretion. Additionally, the marked increase in the endometrial expression of eNOS mRNA and protein around the expected time of implantation with a decline just prior menstruation suggests that endometrial eNOS is regulated by sex steroids, and plays a role in implantation process. In this proposal we will test the hypothesis that sex hormones regulate endometrial eNOS, and NO in turn functions as a mediator of estrogenic influence on cellular proliferation, progesterone's effect in induction of endometrial decidualization. To test our hypothesis we will use in vitro approach using primary human derived endometrial cells to test the direct effects of estrogen progesterone and their combination on eNOS expression and NO secretion (Specific Aim 1) Using pharmacological tools to block the synthesis of endometrial NO, and transfection studies to upregulate eNOS gene expression we will determine if NO mediates E and P actions in the endometrium or independent of sex steroids influence cellular proliferation and endometrial secretion of decidual products (Specific Aims 2 and 3). To complement these studies we will use an ex vivo approach to determine if patients with implantation failures may have endometrial eNOS defects Specific Aim 4). This pilot study should shed light on regulation and function of human endometrial NO pathway, an uninvestigated area of research with profound clinical significance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE TOLERANCE; SIGMA RECEPTOR AS A THERAPEUTIC TARGET Principal Investigator & Institution: Ganapathy, Vadivel; Professor; Biochem and Molecular Biology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The goal of this project is to gather evidence in support of a novel strategy for the induction of immune tolerance, namely to use sigma
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1 receptor as a potential therapeutic target. Sigma 1 receptor is defined as a specific binding site for various psychoactive drugs such as haloperidol and pentazocine. This receptor has been recently cloned and characterized. It is a membrane-bound protein found primarily in intracellular sites. It is expressed in various tissues including immune cells and placenta. There is compelling evidence for an immunosuppressive role of sigma 1 receptor-specific ligands. The role of this receptor in immune function has received increasing attention in recent years as it has become apparent that progesterone is a putative endogenous ligand for this receptor. The goal of this project is to delineate the molecular events involved in the immunosuppressive function of sigma 1 receptor and to investigate the possible role of progesterone in the maintenance of maternal tolerance toward placental allograft. This project will test the following hypotheses: 1) Progesterone and several pharmacological ligands suppress the function and proliferation of T lymphocytes by acting as specific ligands for the sigma 1 receptor; 2) sigma 1 receptor produces its effects by influencing the function of other cellular proteins in T lymphocytes and placenta via protein-protein interaction; 3) Abolition of sigma 1 receptor gene expression by targeted disruption of the gene in a mouse model will lead to maternal intolerance of the placental allograft. Three specific aims are proposed to test these hypotheses. Specific Aim 1 is to study the expression of sigma 1 receptor in quiescent and activated T lymphocytes and to establish the role of this receptor in the suppression of T cell function. This will be done by analyzing the expression of sigma 1 receptor at the molecular and functional level in T lymphocytes before and after activation. The obligatory role of sigma 1 receptor in T cell function will be evaluated by analyzing the biological effects of sigma 1 receptor-specific ligands in sigma 1 receptor-positive (control) and sigma 1 receptor-negative (stable transfectants expressing antisense sigma 1 receptor mRNA) Jurkat cells. Specific Aim 2 is to identify the proteins in human placenta and in T lymphocytes that interact with sigma 1 receptor using the yeast two-hybrid system. Identification of the target proteins that interact with sigma 1 receptor will help to unravel the molecular mechanisms of cell signaling mediated by sigma 1 receptor. Specific Aim 3 is to determine, using sigma 1 receptor knockout mice, whether the absence of the receptor manifests itself as embryo lethality, an inability of the embryo to defend itself against maternal immune system, or as an inability of the maternal immune system to maintain tolerance toward the placental allograft. This project may have significant physiological, clinical, and therapeutic relevance. The proposed studies may lead to a better understanding of the induction of maternal tolerance toward placental allograft and may provide the basis for future efforts to examine the therapeutic potential of sigma 1 receptor-specific ligands as effective immunosuppressants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAMMARY HYPERVIGILENCE
CANCER
RISK:
SOCIAL
ISOLATION
AND
Principal Investigator & Institution: Mcclintock, Martha K.; David Lee Shillinglow Distinguished Serv; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Black women suffer more early, aggressive, lethal breast cancers than do White women of Northern European ancestry. While Blacks of African ancestry may have a higher frequency of cancer promoting genes, e.g. BRCA 1 mutations, this dramatic health disparity may also have psychosocial origins. Our animal model demonstrating larger mammary carcinomas in socially isolated and hypervigilant rats enables us to identify specific mechanisms of ovarian and adrenal function that increase
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Progesterone
the penetrance of mammary cancer promoting genes. Group-living female rats typically develop mammary tumors in late adulthood, in a logarithmic pattern similar to breast cancer dynamics in White women of Northern European ancestry. In stark contrast, socially isolated and hypervigilant rats, with the same genome, develop mammary cancers 40% younger, at 4 times the rate and have larger and more aggressive tumors, similar to breast cancer dynamics in Blacks of African ancestry. Our distinctive animal model permits study of tumor development against the backdrop of normal endocrine function. Because puberty is a sensitive period, we will study characteristics of pubertal ovarian function in socially isolated and group living rats that predict different dynamic patterns of spontaneous ovarian cycles and life-long exposure to estrogen and progesterone. Finally, we will determine how social isolation and hypervigilance alter the timing of mammary gland development relative to ovarian function and pregnancy, increasing sensitivity to carcinogens. In this project we will compare the mammary tumors of socially isolated and group-living rats to determine if both spontaneous and carcinogen-induced (7,12-dimethylbenz(a)anthracene, DMBA) tumors in the two psychosocial conditions are (1) morphologically different (2) have different expression of estrogen and progesterone receptors, and (3) have somatic alterations of rat genes Brcal, ErbB-2/Neu, or c-myc, whose homologs are known to be dysfunctional in Black women with early breast cancer. We will create a tissue bank from all tumors collected in these experiments enabling future collaborative studies by investigators using both proteomic and functional genomic approaches to test additional hypotheses generated by this and other Centers. Insights from this animal model will inform a test of the hypothesis that hypervigilance and social isolation in Black women of African ancestry increase their risk of early, lethal breast cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF STEROID HORMONE ACTION IN BRAIN Principal Investigator & Institution: Tetel, Marc J.; Biology; Skidmore College Saratoga Springs, Ny 12866 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (applicant's abstract): The ovarian hormones, estradiol and progesterone, act in brain to mediate complex behaviors, such as female reproductive behavior in rodents. Understanding how these ovarian hormones act in brain is essential to understanding their role in various mental health disorders such as depression. However, the cellular and molecular mechanisms by which steroid receptors mediate the effects of these hormones in brain are not well understood. Recently, a novel class of proteins has been identified, known as nuclear receptor coactivators, that dramatically enhance the transcriptional activity of steroid receptors. While research has led to a much greater understanding of the molecular mechanisms of these coactivators in steroid receptor action in vitro, very little is known about coactivator function in vivo in brain to regulate hormone-dependent gene expression and behavior. This proposal investigates the function of three important coactivators, Steroid Receptor Coactivator-1 (SRC-1), SRC-3 and CREB Binding Protein (CBP), in estrogen receptor (ER) action in brain and the regulation of behavior. Aim 1 will determine if SRC-3, which has recently been shown to be essential for female reproductive physiology, is expressed in steroid receptorcontaining neurons in brain regions known to regulate reproductive behavior. In support, we have found that SRC-1 and CBP are expressed in steroid sensitive cells in behaviorally-relevant brain areas. Aim 1 will also test the hypothesis that these three coactivators physically interact with neural ER in a hormone-dependent manner. Aim 2 will use antisense oligonucleotides to suppress SRC-1, SRC-3, and CBP expression to
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investigate the function of these coactivators in ER-mediated activation of three behaviorally-relevant genes: the progesterone receptor, preproenkephalin and oxytocin receptor genes. Aim 3 will use the same antisense approach to test the hypothesis that these nuclear receptor coactivators are critical for the expression of estradiol-induced female reproductive behavior. Consistent with these hypotheses, our preliminary results indicate a functional role for these coactivators in estrogen-dependent gene expression in brain and hormone-dependent reproductive behavior. These studies will greatly enhance our understanding of how these novel coactivators function with steroid receptors in brain to activate behaviorally-relevant genes and regulate complex behaviors. Finally, these nuclear receptor coactivators have been implicated in human disorders, including a form of mental retardation (Rubinstein-Taybi Syndrome) and hormone-dependent diseases such as breast cancer. Studying how these coactivators function in vivo, and moreover in brain, will greatly increase our limited knowledge of the role of these coactivators in human disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
MECHANISTIC
STUDIES
OF
PROGESTERONE
RECEPTOR
Principal Investigator & Institution: Bain, David L.; Assistant Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The long-term goal of this research is to elucidate the molecular mechanisms underlying eukaryotic gene regulation. Focus is centered on the mechanisms by which human progesterone receptors (PR) cooperatively bind to complex promoters, and the role of hormone agonists and antagonists in regulating these reactions. A further goal is to determine the principles by which the associated structural transitions are propagated to neighboring domains. PR co-exist as two functionally distinct isoforms: an 83 kD A-receptor and a 99 kD B-receptor. The two isoforms are identical, except that the B-receptor has an additional 164 amino acids at its N-terminus. The B-receptor often functions as a strong transcriptional activator, while the A-receptor generally acts as a weak activator. It is hypothesized that this difference arises through the ability of the B-receptor to bind cooperatively at PR-regulated promoters. Mechanistically, the B-unique residues impose a hormone-dependent conformational constraint upon the remainder of the receptor. This constraint causes changes in PR structure and stability changes that can include dramatic disorder-order transitions, resulting in cooperative DNA binding. It is proposed that a role of antagonists is to decouple these linkages by stabilizing ineffective conformations within the PR hormone-binding domain. This hypothesis, and the underlying mechanism, will be examined by carrying out the following studies: Aim 1 - The energetics of selfassembly for both isoforms in the presence and absence of progestin agonists and antagonists will be determined using analytical ultracentrifugation. Aim 2 - A rigorous thermodynamic analysis of the interactions of each PR isoform with the multi-site mouse mammary tumor virus promoter will be determined using quantitative DNAse footprinting. Aim 3 - The changes in isoform structure and stability associated with ligand and DNA-binding will be mapped using hydroxyl radical proteolytic footprinting, CD spectroscopy and microcalorimetry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Progesterone
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Project Title: MENSTRUAL PHASE AND NEURAL CONTROL OF SKIN BLOOD FLOW Principal Investigator & Institution: Johnson, John M.; Professor; Physiology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the applicant's abstract): Reflex control of the cutaneous circulation is both of thermoregulatory and of non-thermoregulatory origin and occurs via sympathetic vasoconstrictor and sympathetic active vasodilatory mechanisms. The applicant has previously shown that each of these 2 efferent systems is subject to control by internal temperature, skin temperature, exercise-associated reflexes, and baroreflexes. Steroidal changes accompanying the phases of the menstrual cycle are known to act as background modifiers of the thermoregulatory control of skin blood flow. The PI's working hypothesis is that in the luteal phase, progesterone inhibits active vasodilation by shifting to a higher internal temperature threshold for its initiation and elevates vasoconstrictor activity for any given body temperature as well. Elevated estrogen levels in the ovulatory phase are hypothesized to have directionally opposite effects on vasoconstriction and active vasodilator function. Through selective local blockade of vasoconstrictor function the applicant will examine changes in active vasodilator function among menstrual phases. Such effects would provide mechanisms for the well-documented phasic changes in basal internal temperature and in the control of the cutaneous circulation through the menstrual cycle. The applicant will also seek evidence for the roles of progesterone and estrogen in these phasic changes by taking advantage of the normal fluctuations of steroid levels among follicular (both low), ovulatory (estrogen elevated), and luteal (both elevated) phases to find how those hormonal patterns affect the control of the vasodilator and vasoconstrictor pathways. These studies will be complemented by examinations of alterations in control of the vasoconstrictor and vasodilator pathways between active and placebo phases of oral contraceptives. The applicant will evaluate peripheral contributions by these steroids in vasomotor function by testing whether vasoconstrictor responses to controlled application of norepinephrine or vasodilator responses to direct application of acetylcholine are dependent on the phase of the menstrual cycle. This question will be further addressed by finding if the level of skin blood flow in areas free of autonomic influences (via cutaneous nerve block) and in areas with intact innervation vary among phases of the menstrual cycle or between phases of oral contraceptive use. The role of prostaglandin synthesis in the upward shift of the thermoregulatory control of the active vasodilator system will also be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MINERALOCORTICOID HYPERTENSION
RECEPTOR
PHYSIOLOGY
IN
Principal Investigator & Institution: Geller, David S.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: (Adapted from the applicant's abstract) The human mineralocorticoid receptor (MR) serves as the final effector of the renin-angiotensin-aldosterone pathway and is a key regulator of sodium homeostasis in the distal nephron. These investigators recently described a novel form of human Mendelian hypertension caused by a gain of function mutation novel form of human Mendelian hypertension caused by grain of function mutation in MR. The mutation results in constitutive activity of the receptor
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and alters receptor specificity such that progesterone, normally an MR antagonist, functions as an agonist. Consistent with the dramatic rise in progesterone levels in pregnancy, carriers of this mutation develop severe pregnancy-related hypertension. Previous studies indicate that bending of helix 3, and that this mutant achieves the 210H independent bending of helix 3 via creation of a novel van der Waals interaction between helix 3 and helix 5. The observations that this helix 3- helix-5 interaction is highly conserved among diverse nuclear receptors indicated its general role in receptor activation. In this grant, we propose both biochemical and clinical studies to augment our understanding of MR function in human physiology and hypertension. They will assess the proposed model for MR activation and identify specific residues necessary for MR specificity and activity. Furthermore, they will identify nuclear co-regulators required for MR activity and identify the biochemical requirements for MR activation. Clinically, they propose to determine the prevalence of disease causing MR mutations in a variety of clinical situations and finally, determine extra-renal effects of an activated MR in patients carrying this mutation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF UTERINE RECEPTIVITY Principal Investigator & Institution: Demayo, Francesco; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The overall objective of this proposal is to define the essential molecular mechanisms that underlie uterine receptivity. Ovarian-derived progesterone is known to be an indispensable signaling molecule in the preparation of the uterus for embryo attachment and subsequent invasion Using the progesterone receptor knockout mouse in combination with DNA microarray technology, we recently demonstrated that the morphogen, Indian hedgehog, Ihh, is expressed in the murine uterus and, importantly, regulated by progesterone via its nuclear receptor. This important observation forms the basis of the following hypothesis: The Indian hedgehog signaling pathway is an integral regulatory axis for the preparation of the uterus for embryonic implantation. This proposal will establish a novel mouse model for the reproductive tissue specific ablation of Ihh and then evaluate the impact of Ihh ablation on uterine function. Then, this proposal will investigate the expression of members of the Ihh signaling cascade in human endometrial tissue. Then, this proposal will investigate the expression of members of the Ihh signaling cascade in human endometrial tissue. The goals of this proposal will be achieved by using Homologous recombination in ES cells to insert Cre recombinase into the progesterone receptor locus. This mouse will be used to ablate Ihh specifically in the uterus and mouse reproductive tissues. The physiologic and molecular impact of Ihh ablation in the uterus will then be investigated. Finally the expression of Ihh in the receptive and non-receptive human endometrium will be investigated. The contribution of this proposal to the U01 consortium will be the establishment of a novel animal model that will facilitate the investigation of the role of regulatory molecule sin uterine receptivity, as well as, the investigation of the role and expression of members of the Ihh signaling cascade in mouse and human receptivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR AND CELLULAR BIOLOGY OF HIV IN WOMEN Principal Investigator & Institution: Greene, Warner C.; Director; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103
28
Progesterone
Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: (Abstract Provided by Applicant) Heterosexual transmission of HIV is responsible for more than 90% of the HIV infections occurring in the world. Women, compared with men, experience at least an eight-fold higher risk of HIV infection following vaginal intercourse. However, our understanding of how HIV infection occurs in the lower female genital tract remains rudimentary. For example, the identity of the first cell infected within the vaginal mucosa is controversial (Langerhans cell versus subepithelial dendritic cell). Transcytosis of virus through the epithelium may also occur and subepithelial dendritic cells expressing DC-SIGN may simply bind and ferry HIV to regional lymph nodes in the absence of active viral replication. We now propose to systematically study the molecular and cellular basis for heterosexual transmission of HIV by inoculating a cervical vaginal organ culture system with green fluorescent virions. We will monitor how these virions navigate across this mucosal surface and identify the initial cellular targets of interaction or infection. We will also study isogenic viruses differing only in their chemokine receptor tropism (CCR5 versus CXCR4) exploring whether the preferential transmission of R5-tropic viruses between humans is restricted at the level of the mucosal surface. We will analyze matched viruses containing clade E versus clade B env genes testing the clinical suggestion that clade E viruses spread more efficiently by heterosexual transmission. Additionally, we will compare the infectivity of viruses containing mutations in the protease gene induced by potent protease inhibitors or in the nef gene linked to the selective loss of CD4 or MHC class I receptor downregulation. Finally, we will evaluate whether treatment of the cervical vaginal organ cultures with estrogen or progesterone reproducibly influences their susceptibility to infection with HIV (Specific Aim 1). In a second line of investigation, we will explore the unexpected ability of the HIV-1 Vpr gene product to function as a transcriptional coactivator with the glucocorticoid receptor testing whether Vpr similarly coactivates estrogen, progesterone, or androgen nuclear hormone receptor activity. We will also examine whether these hormones alone or in combination with Vpr alter transcriptional activity of the HIV-1 LTR in the context of normal chromatin structure or induce the activation of HIV replication in latently infected cells (Specific Aim 2). Finally, we will explore the protein-transducing properties of soluble Vpr that permit this protein to efficiently enter and function in uninfected host cells. Synthetic, full-length soluble Vpr will be tested for coactivating effects with the glucocorticoid receptor when added extracellularly and analyzed for its ability to enhance progesterone mediated inhibition of MIPl-a. MIPl-b, and RANTES antiviral chemokine secretion by activated CD8+ T cells (Specific Aim 3). Through these studies, we seek to gain a clearer understanding of the biology underlying heterosexual transmission of HIV in women and the potential interplay of HIV Vpr with various female sex hormones that may modify the replication potential of the virus in a gender specific manner or alter the local permissiveness of the cervical vaginal mucosa to virus infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF ION CHANNEL IN CELL MEMBRANES Principal Investigator & Institution: Cahalan, Michael D.; Professor; Physiology and Biophysics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001; Project Start 15-SEP-1978; Project End 31-MAR-2006 Summary: This project focuses on molecular properties and regulation of ion channels in T lymphocytes, taking advantage of parallel advances in electrophysiology, molecular
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biology and video imaging techniques. Our goal is to understand the role of ion channels in the immune response. Using patch-clamp techniques, we have characterized a diverse set of functionally significant ion channels that are differentially expressed depending on the developmental and activation state. Through the proposed experiments, we plan to continue our studies of three main channel types. A voltagegated K+ channel, Kv1.3, is functionally important in resting T cells. Using site-directed mutants, we will map the channel's inner vestibule with tethered blockers and characterize the action of progesterone. Ca2+- activated K+ channels, encoded by IKCa1 in human T cells and SKCa2 in Jurkat T cells, regulate membrane potentials during [Ca2+]i signaling. IKCa1 is up-regulated in activated T cells and is required for sustained proliferation. We will probe the mechanism of Ca2+ sensing by pre-bound calmodulin. Dominant- negative constructs will be developed to suppress channel expression. Calcium signaling and gene expression depend crucially on Ca2+ releaseactivated Ca2+ (CRAC) channels that open when intracellular Ca2+ stores are depleted. We will investigate the activation mechanism of this channel, with single-channel resolution, investigate block by polyamines, and use a dominant-negative strategy to test for candidate genes. Finally, using highly specific and potent blockers developed during the previous grant period, we will test for functional roles of K+ channels in [Ca2+]i signaling, cytokine release, cell proliferation, and chemotaxis. Through the proposed experiments we hope to define mechanisms that regulate ion channels and corresponding cell functions that underlie the immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS FOR NICOTINE'S INTERACTION WITH STRESS Principal Investigator & Institution: De Biasi, Mariella G.; Neuroscience; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): In this application we will examine the interaction between chronic stress and nicotine by studying behavior, autonomic responses, and hormone and neurotransmitter levels in several mouse models. This proposal arises from the finding that smokers often report an anxiolytic effect of cigarettes, and stressrelated disorders such as depression, posttraumatic stress syndrome, and anxiety are often associated with chronic nicotine use. The influence of nicotine might depend on its ability to both activate and desensitize nicotinic acetylcholine receptors (nAChRs) in stress-related neural circuits. That basic action of nicotine, in turn, depends on the subunit composition of nAChRs that modulate those neural circuits. A related phenomenon is that chronic exposure to stress produces neural adaptations in brain regions that are associated with the rewarding effects of nicotine. To determine which nAChR subtypes are important for the interaction between stress and nicotine's actions, we will expose nAChR mutant mice lacking one or combinations of nAChR subunits to chronic stress. Our experiments will capitalize on the anxiety-related phenotypes that we and others have reported in nAChR mutant mice. The application also will address gender differences in the stress/nicotine interaction. Gender plays a major role in stress integration and stress-related affective disease states. We will investigate gender-related mechanisms by performing our experiments in ovariectomized and orchiectomized animals. Particular attention will be paid to the role of progesterone in the physiological mechanisms underlying stress by analyzing mice lacking the progesterone receptors A and B alone or in combination. The proposal will begin by examining the effects of chronic stress on nAChR mutant mice and their wild-type littermates. The other two main aims will examine the interaction between stress and nicotine. The second aim will
30
Progesterone
examine how chronic stress affects the response to acute doses of nicotine. The third aim will examine the behavioral and physiological manifestations produced by chronic nicotine with and without concomitant exposure to stress. Our in vivo studies will combine behavioral testing with telemetry and the measurement of plasma levels of stress hormones. The in vitro studies will use in situ hybridization, autoradiography, and immunohistochemistry techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS OF BREAST DEVELOPMENT AND NEOPLASIA Principal Investigator & Institution: Weinberg, Robert A.; Member/ Professor; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2003 Summary: (Applicant's Description) An understanding of the molecular mechanisms leading to human breast cancer development will come from insights into how the breast tissue develops normally. Such insights can be most easily obtained in the mouse breast, the development of which is governed by biochemical regulators very similar to those that operate to program human breast morphogenesis. Breast development is governed by bi-directional communication between the mammary epithelium and surrounding stroma. The present research examines three signalling pathways that appear to be essential for normal breast development and appear to be disrupted during cancer pathogenesis. First, estrogen acting through its receptor in normal mammary epithelial cells (MECs) does not appear to be mitogenic but has acquired such powers in many human breast carcinoma cells. The proposed research examines the possibility that these powers result from the inappropriate expression of a co-activator of the receptor that is not normally expressed in MECs. A second aspect of breast signalling involves the progesterone receptor, which is responsible for sidebranching of mammary ducts. The present research examines the possibility that this receptor, when activator by progesterone, causes expression of hepatocyte growth factor in nearby stroma; this factor then acts on MECs to induce ductal sidebranching. A third line of research examines the possibility that prolactin, acting through its receptor in MECs, is able to induce the production of the neuregulin growth factor in nearby stromal tissue; once released, the neuregulin causes MEC proliferation leading to the formation of alveoli. The latter pathway is often subverted in human mammary carcinoma cells that express the HER2 receptor of neuregulin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROENDOCRINE BASES OF REPRODUCTIVE BEHAVIOR Principal Investigator & Institution: Etgen, Anne M.; Professor; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-DEC-2001 Summary: (Adapted from the investigator's abstract): The ovarian hormones estradiol (E) and progesterone (P) act in the hypothalamus and preoptic area (HPOA) to stimulate the preovulatory release of pituitary gonadotropins and coordinate the expression of reproductive mating behavior, namely lordosis by the female through the action of norepinephrine (NE). The goal of the proposed research is to examine the molecular mechanisms by which estradiol and progesterone modulate signal transduction on alpha1-and beta-adrenoceptors in the HPOA and to relate these to the expression of reproductive behavior. Specific Aim 1 will test the hypothesis that estradiol elevates alpha1B-adrenoceptors in populations of HPOA neurons that express
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31
ER. Immunocytochemical approaches will be employed to determine: 1) whether E increases alpha1B-adrenoceptor protein in regions of the HPOA that also express ER; 2) whether A1B - adrenoceptors and ER are colocalized in some or all of these neurons; and 3) whether hypothalamic neurons expressing alpha1B-adrenoceptors project to the midbrain central gray (MCG). Specific aim 2 will test the hypothesis that in the HPOA of E-primed females P will switch alpha1 adrenoceptor signaling from activation of phospholipase C to calcium- dependent activation of the nitric oxide (NO)/soluble guanylyl cyclase pathway. Support for this hypothesis is derived from the observation that alpha1-adrenergic activation of NO synthesis influences the preovulatory release of LH and because expression of reproductive behavior in E+P treated female rats is inhibited by NO synthetase inhibitors and inhibitors of soluble guanylyl cyclase. Specific aim 3 will test the hypothesis that E increases the expression of one or more protein kinase C (PKC) isoenzymes in the HPOA. PKC is a major downstream mediator of alpha1-adrenergic signal transduction; hence, induction of PKC could further amplify alpha1-adrenergic signaling in the HPOA. Experiments will utilize assays of PKC catalytic activity as well as phorbol ester binding and Western Blots to identify the separate isoenzymes. Specific Aim 4 will test the hypothesis that E regulates molecules involved in adrenergic receptor-G protein coupling. Molecular biological and immunological methods will be used to determine the effects of E on: 1) mRNA and protein levels of b-adrenergic receptor kinase 1 and 2 (b-ARK1, and b-ARK2) and 2) the mRNA and protein levels of b-arrestin1 and b-arrestin2. These are significant questions because b-ARKs and b-arrestins impede the interactions of b-adrenergic, a2-adrenergic and u-opioid receptors with G proteins, and they find that E treatment decreases the function of all three of these receptors in the HPOA with measurably downregulating the receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROENDOCRINE CONTROL OF PUBERTY Principal Investigator & Institution: Foster, Carol M.; Associate Professor; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Despite extensive investigation of the hormonal changes underlying the pubertal transition, may questions remain regarding how the restrained pattern of childhood gonadotropin secretion increased in the face of rising sex steroid concentrations to exhibit the variable patterns of adulthood that support menstrual cyclicity and ovulation. Recent data indicate that boys have girls have differences in pubertal gonadotropin secretion. LH secretion appears to respond differently to sex steroid feedback in girls compared to boys, and FSH concentrations are relatively less suppressed in childhood in girls than in boys. The gonadotropins, and particularly FSH, may be regulated in changes in the gonadal peptides, activin, inhibin and follistatin. Exploration of the roles of these peptides in regulation of gonadotropin secretion has been hampered until now by lack of specific assays. In this research, novel assays and experimental treatments will be employed to investigate the mechanisms of puberty in girls, testing the hypothesis that gonadotropin secretion in girls is altered in response to the changing ovarian sex steroid and ovarian peptide milieu. Specifically, it is hypothesized that, during puberty there is a switch in the neuroendocrine responses to sex steroid feedback involving changes in opioid tone and a more predominant role of the pituitary. It is also hypothesized that FSH secretion is progressively inhibited by the developing gonad's increasing secretion of inhibition and follistatin. The hypothesis will
32
Progesterone
be evaluated by examining the interactions of LH, FSH and the ovarian secretions, estradiol inhibin A and B, and follistatin, during puberty in girls: 1) determining the role of estradiol and/or progesterone in the development of opioid inhibition of GnRH secretion using sex steroid replacement studies; 2) examining the changes in hypothalamic and pituitary sensitivity to estradiol between adult women and pubertal girls; 3) relating changes in serum inhibin A and B, activin A, and follistatin concentrations to serum gonadotropin and sex steroid concentrations to serum FSH concentrations during gonadotropin- dependent and independent precocious puberty in girls. Puberty results in remarkable changes in the neuroendocrine control of the reproductive hormones, and study of these changes should lead to a better understanding of the pathophysiology of reproductive abnormalities and infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROREHABILITATION PREGNENOLONE
WITH
PROGESTERONE
&
Principal Investigator & Institution: Wright, David W.; Emergency Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): There are about 5.3 million people in this country living with a range of disabilities caused by traumatic brain injury, and about 25-30% of those people are unable to return to work one year later. At present, there are no effective clinical treatments currently available to the victims of traumatic brain injuries that can repair the primary and secondary damage caused by the cascade of cytotoxic damage unleashed by the initial insult. Obviously, a safe, low cost and effective treatment for such a significant health problem is worth addressing. Numerous reports have documented the role of neurosteroids in immediate post-injury neuroprotection. However, few studies have examined the effect of these steroids as a treatment after the acute phase. We are particularly interested in the effect of progesterone long-term because it is currently being tested in a human clinical trial as an acute phase neuroprotectant. Extensive preclinical trials have shown that progesterone is neuroprotective when administered shortly after injury. However, at least two of the potential mechanisms (inhibition of NMDA transmission and stimulation of GABAA receptors), by which progesterone exhibits neuroprotection, could potentially worsen subacute rehabilitation and subsequent long-term recovery. Conversely, pregnenolone, the precursor of progesterone, exhibits opposite effects with respect to NMDA and GABAA modulation and could enhance neurorehahilitation. We propose to determine the effects of progesterone and pregnenolone when treatment is delayed after injury in animals. The data gathered would provide information regarding the potential utility of these neurosteroids in subacute or long-term treatment conditions. In addition, should progesterone prove to be an effective neuroprotectant in the human clinical trial, it will be necessary to know how long treatment should be maintained and whether long-term treatment enhances or deters post-injury rehabilitation. There is a growing body of evidence that both progesterone and pregnenolone can also stimulate remyelination of damaged nerve cells and that they also have the potential to stimulate neuronal repair after the initial injury cascade has long subsided. This means that these steroids, both of which are synthesized in the brain, may be beneficial as adjunct therapies for long-term rehabilitation. We propose to investigate the role of the neurosteroids progesterone (PROG) and pregnenolone-sulfate (PREGS) as putative treatment for traumatic brain injury during the rehabilitation phase of recovery in both male and female subjects.
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Therefore, we will examine two delayed treatment paradigms (7 days & 28 days post injury) on the recovery process at the behavioral and morphological levels of analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ONTOGENY MECHANISMS
OF
IDENTIFIABLE
NEURONS
AND
OPIOID
Principal Investigator & Institution: Gintzler, Alan R.; Professor; Biochemistry; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2002; Project Start 01-MAY-1980; Project End 31-MAR-2007 Summary: (provided by applicant) Gestation, in laboratory animals and women, is accompanied by a hormonally activated antinociception that is predominantly driven by spinal dynorphin/K- and enkephalin/6- analgesic systems. Notably, this antinociception appears not to be subject to tolerance lormation. Spinal dynorphin tone, augmented during pregnancy and its hormonal simulation (HSP), results from the offset of its negative modulation by endogenous spinal opioids and nociceptin (orphanin FQ; N/OFQ). In fact, in HSP animals, the delta-opioid inhibition of dynorphin release reverses to an enhancement. This renewal application proposes to build on these observations to elucidate mechanistic underpinnings of the antinociception of pregnancy and HSP. The organizing hypothesis is that interactions between visceral afferent input and ovarian sex steroids are causally associated with altered regulation of spinal opioid action. This results in the reciprocal feed-forward regulation of dynorphin/K and enkephalin/delta spinal opioid pathways and the ovarian steroiddependent amplification of opioid neuronal transmission. The specific objectives are to (1) Determine the influence of pregnancy and 17-betaestradiol (E2) and progesterone (P) on analgesic responsiveness to intrathecal (i.t.) delta-opioid agonists and the receptor profile thereof, (2) Determine whether or not the pregnancy profile of E2/P activates an enkephalin spinal antinociceptive system analogous to its effects on spinal dynorphin; the influence of E2/P, N-OFQ, opioids and interactions thereof on the in vitrorelease of lumbar spinal enkephalin will be investigated, (3) Determine the sequelae of sustained ovarian sex steroid treatment of orchidectomized sexually mature male rats on spinal opiold release: compare and contrast with females, (4) Determine the relevance of augmented afferent tone to the blunted formation of tolerance to endogenous opioids and the recently discovered E2/P-induced 'feed forward' opioid antinociception and (5) Determine the effect of the pregnancy profile of E2/P on opioid tolerance development to i.t. opiolds. Insights obtained from these experiments should point the way to the development of gender-based pharmacotherapies for the treatment of chronic pain (notoriously more prevalent in women than men), the usefulness of which is not restricted by the extreme loss of potency over time, the bane of narcotic utilization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPIOID REGULATION OF GNRH PULSES Principal Investigator & Institution: Lehman, Michael N.; Professor; Cell Biol, Neurobiol/Anatomy; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: Gonadotropin releasing hormone (GnRH) neurons play a central role in the control of mammalian reproductive function. Changes in the pulsatile secretion of GnRH and luteinizing hormone (LH) are critical for the regulation of events leading to ovulation, as well as to the inhibition of ovulation prior to puberty and during other physiological periods of infertility. Based on recent data, we have developed a working
34
Progesterone
hypothesis for the control of pulsatile GnRH/LH secretion by endogenous opioid peptides (EOP). This hypothesis suggests that one of the EOP systems in the brain, the dynorphin-kappa receptor system, acts in the mediobasal hypothalamus (MBH) to mediate the inhibitory effect of progesterone on GnRH pulse frequency during the luteal phase of the ovine estrous cycle. In the first aim, we will test this hypothesis by determining if dynorphin neurons contain progesterone receptors; progesterone treatment increases dynorphin mRNA and/or peptide levels; and removal of dynorphin blocks the ability of progesterone to inhibit LH pulse frequency. In the second aim, we will delineate the anatomical substrates of these interactions by determining whether GnRH neurons express kappa receptors, and whether dynorphin cells that project to the median eminence contain progesterone receptors and form axo- axonic contacts with GnRH terminals. Finally, in the third aim, we test the hypothesis that dynorphin neurons, acting via kappa receptors, are involved in the generation of GnRH pulses by determining whether kappa receptor antagonists or dynorphin antisera alter the shape of GnRH pulses. These questions will be explored using the sheep as an animal model because of advantages which include the similarity of its estrous cycle to the human menstrual cycle and the ability to directly monitor GnRH pulses without anesthesia. In addition, EOP have been shown to play a major role in mediating progesterone negative feedback during the luteal phase in humans as well as sheep. Thus, these studies may lay the foundation for the development of better treatments for pathological disruptions of reproductive function, may lead to better clinical management of follicular development, increasing the efficiency of assisted reproductive technologies, and may provide the basis for the design of novel contraceptive techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OVARIAN FAILURE IN LH/HCG RECEPTOR KNOCKOUT ANIMALS Principal Investigator & Institution: Rao, Ch V.; Professor and Director; Obstetrics and Gynecology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: Both IIpo Huhtaniemi's and our group recently succeeded in generating LH receptor knockout mice by gene targeting in embryonic stem cells. Although this gene knockout was not lethal, it rendered animals infertile. While ovaries of wild- type and heterozygous animals contained LH receptors, ovaries of homozygous littermates contained none. Also, while ovaries of wild-type and heterozygous animals were normal in size and contained preovulatory follicles and corpora lutea, the ovaries of homozygous littermates were small and pale with an arrest of follicular growth at the antral stage. Preliminary studies indicated this arrest could, at least partly, be due to a decrease in telomerase levels and a consequent increase in apoptosis. In homozygous animals, LH levels were markedly elevated, FSH levels were moderately elevated, and estradiol and progesterone levels decreased but were not totally suppressed. Knockout animals can be extremely useful in answering a number of unknowns in LH biology. For example, we could learn: 1) whether LH actions are required for the presence of normal numbers of primordial, primary, preantral and antral follicles; 2) whether FSH can induce follicular growth and ovulation in the total absence of LH actions; 3) what role LH signaling plays in ovarian development and function from one week after birth through one year of age; 4) what ovarian actions of LH are mediated by estradiol, progesterone and testosterone; 5) identify and characterize previously unidentified ovarian genes that are regulated by estradiol, progesterone, testosterone, LH or by their combination; and 6) whether using gene therapy to introduce LH receptors into ovaries
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of null animals makes them cyclic and ovulate but still not get pregnant because they do not have LH receptors in the uterus. These are only a few examples of how the use of null animals could advance our current understanding on the role of LH in different ovarian functions. We propose three specific aims in this application: 1) Investigate structural and functional defects in ovaries of 7-day, 25-day, 60-day and 1-year old null mice to compare with their age- matched, wild-type and heterozygous siblings. 2) Investigate whether estradiol, progesterone and testosterone replacement therapy can correct structural and functional defects in ovaries of LH receptor knockout animals. 3) Determine whether retroviral mediated LH receptor gene transfer can correct structural and functional defects in ovaries of null animals so they become cyclic and ovulate even though pregnancy may not occur due to the absence of LH receptors in the uterus. There are several strengths in this proposal. Foremost is studying LH biology using knockout technology. Second is using steroid hormone replacement and gene therapies. Third is using cDNA expression arrays, a powerful technique in gene expression analysis. All techniques to be used in the proposed studies have already been established to obtain preliminary data presented in the proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXYTOCIN REGULATION BY NEUROSTEROIDS & GABA-A RECEPTOR Principal Investigator & Institution: Amico, Janet A.; Professor; Pharmaceutical Sciences; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Oxytocin(OT) is a nonapeptide that functions as both a hormone and a neuropeptide during certain reproductive processes and behaviors. OT is essential for milk ejection during lactation, enhances uterine contractility at parturition and induces maternal behavior in the rat. Maternal behavior in most mammals is stimulated by the hormonal milieu of late pregnancy. In the rat, rising levels of estrogen (E) superimposed on the late-term decline in progesterone (P), stimulate maternal behavior. The ovarian steroid exposure which optimally stimulate maternal behavior (declining P in the setting of E priming) also enhances levels of oxytocin (OT) mRNA and OT peptide in the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus, which are the sites of synthesis of over 95% of the OT formed within the CNS. Progesterone plays a key role in the regulation of both maternal behavior and OT expression by mechanisms which are not well understood. P can affect neuronal transmission by binding to its cognate nuclear receptor (PR), which acts as a hormone- dependent transcription factor, or by binding to the membrane bound GABAA receptor complex. We hypothesize that changes in OT expression in the PVN and SON of the steroidtreated and pregnant rat are regulated by P-mediated plasticity in subunits of the GABAA receptor and/or by alterations in concentrations of neurosteroids. Increased OT expression within magnocellular and/or parvocellular neurons of the PVN may in turn facilitate the onset of maternal behavior. The specific aims of this proposal are as follows:1-administer allopregnanolone, or its agonist, ganaxolone, or inhibitors of allopregnanolone formation to the steroid-treated ovariectomized rat and measure changes in OT mRNA and OT peptide in the PVN and SON of the hypothalamus; 2administer allopregnanolone or its agonist, ganaxolone, or block formation of allopregnanolone and measure indices of maternal behavior, hypothalamic OT mRNA and OT peptide in rats receiving a steroid treatment known to induce maternal behaviors and; 3-measure by in situ hybridization the relative abundance of OT mRNA and GABAA receptor subunit mRNAs and measure by in vitro receptor
36
Progesterone
autoradiography 3[H]muscimol GABAA receptor binding in the hypothalami of the steroid- treated or allopregnanolone (ganaxolone)- treated ovariectomized rat and the pregnant or lactating rat; 4 - administer an antisense oligonucleotide to OT or an OT antagonist i.c.v. to the steroid-treated ovariectomized rat or the pregnant rat and measure indices of maternal behavior and levels of hypothalamic OT mRNA and OT peptide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARACRINE DYSREGULATION OF OOCYTE COMPETENCE IN PCOS Principal Investigator & Institution: Dumesic, Daniel A.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Polycystic ovary syndrome (PCOS) in women is characterized by anovulation, LH hypersecretion, hyperandrogenism and insulin resistance. As the most common endocrinopathy in females, affecting 4-7% of reproductive-aged women, and as a frequent cause of infertility, accounting for 75% of anovulation, PCOS has staggering adverse physiological, psychological and financial consequence on reproduction in women. During gonadotropin stimulation for in vitro fertilization (IVF), PCOS women experience decreased fecundity and increased pregnancy loss. Since experimental investigation of oocyte and embryo development in humans is limited by ethical constraints, we have developed the prenatally androgenized (PA) female rhesus monkey as a model for PCOS. PA female monkeys undergoing follicle stimulating hormone (FSH) therapy for IVF exhibit LH hypersecretion, circulating insulin excess, an exaggerated shift in intrafollicular steroidogenesis from estradiol (E2) and androstenedione (A4) to progesterone (P4), and impaired embryo development beginning with embryonic genome activation. Because insulin enhances FSH-induced granulose cell differentiation, leading to LH-induced P4 production, we hypothesize that a) premature follicle luteinization and b) impaired oocyte developmental competence in PA monkeys are caused by adverse effects of hyperinsulinemia on follicle maturation. We predict that such abnormalities in PA monkeys are reversed by improved insulin sensitivity from weight loss through dietary restriction and will test our prediction in Specific Aims 1 and 2. Based upon data from our recognized nonhuman primate model of PCOS, we also hypothesize that c) premature follicle luteinization is a cause of poor oocyte developmental competence in PCOS women undergoing FSH therapy for IVF. We predict that granulosa cell dysregulation of LH receptor, insulin receptor (IR) and growth differentiation factor-9 (GDF-9) transcription from premature follicle luteinization causes poor cumulus cell proliferation in PCOS women (Specific Aim 3). We further hypothesize that d) meiotically-competent and meiotically-incompetent oocytes of PCOS patients are impaired in expression of GDF-9 and other developmentally relevant messenger ribonucleic acids (mRNAs) (Specific Aim 4). The long-term objectives of this proposal are to: 1) define molecular markers of oocyte developmental competence that enhance IVF pregnancy outcome by improving rates of embryo cleavage and blastocyst formation; while minimizing pregnancy loss in women with PCOS and other insulin resistant states, such as obesity and Type II diabetes, and 2) to provide additional, unique, insight into the transgenerational effect of PCOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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37
Project Title: PHARMACOLOGY OF NONSTEROIDAL ANDROGEN RECEPTOR LIGANDS Principal Investigator & Institution: Dalton, James T.; Associate Professor; None; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: During studies in our laboratory to search for electrophilic affinity ligands for the androgen receptor (AR), we discovered that structural modification of known nonsteroidal anti-androgens results in androgenic activity. These compounds represents a new class of androgenic drugs, and were the first reported non-steroidal AR agonists. Others have recently confirmed the ability of non-steroidal ligands to stimulate ARmediated transcription. The studies proposed herein are a pivotal extension of research in this field based on recently reported structure- activity relationships and our experience binding, pharmacology, and pharmacokinetics of non-steroidal AR ligands. Our studies are divided into three independent efforts: 1. Design and Synthesis and Novel Non-steroidal AR Ligands. We synthesized a series of bicalutamide analogs that bind the AR with high affinity and induce androgen receptor-mediated transcriptional activation. We proposed herein a strategy for rational drug design and organic syntheses of additional non-steroidal androgens based on literature data and preliminary data obtained in our laboratories. 2. In Vitro Functional Activity and Specificity for AR. We will examine AR binding affinity and AR-mediated transcriptional activation of potential non-steroidal androgens in cells transfected with the human. AR. A key element in evaluation of these drugs will be the ability to discriminate between AR and other steroid receptors, such as glucocorticoid (GR), progesterone (PR) and estrogen receptors (ER). Whole cell binding experiments and transcriptional activation studies will be conducted in cells transfected with the GR, PR., ER and AR to examine receptor specificity. 3. Androgenic and Anabolic Activity in Whole Animals. The utility of these compounds is ultimately dependent on their ability to stimulate androgen-mediated growth in whole animals. We will conduct integrated pharmacokinetic and efficacy studies in castrated and intact male rats to determine the in vivo pharmacologic activity, bioavailability, and pharmacokinetics of these drugs. The overall goal of these studies is to develop structure-activity relationships based on the physicochemical and pharmacokinetic properties of these drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGY PROGESTERONE
OF
HYPOTHALAMIC
NEUROSTEROIDAL
Principal Investigator & Institution: Micevych, Paul; Professor; Neurobiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Neurosteroids, steroids synthesized in the brain, have been implicated in functions ranging from stress, depression, anxiety, to cognition. One neurosteroid is progesterone, a classic sex hormone involved in the regulation of reproduction. Although the CNS has the capacity to synthesize progesterone, to date it has appeared that only peripheral progesterone, from the ovaries and adrenals, regulates reproduction. Our preliminary studies have demonstrated that estrogeninduced hypothalamic progesterone synthesis is sufficient to initiate reproductive events necessary for ovulation and copulation. Estrogen stimulation of ovariectomized and adrenalectomized (ovx/adx) rats increased hypothalamic progesterone levels. In
38
Progesterone
such animals, estrogen induced lordosis behavior and progesterone dependent proceptive behavior. Similarly, estrogen stimulation of ovx/adx rats induced a luteinizing hormone (LH) surge. In these rats, blocking 3beta-hydroxysteroid dehydrogenase (3beta-HSD), the enzyme that converts pregnenolone to progesterone, prevented the LH surge. Estrogen stimulates astrocytes in culture to synthesize progesterone, suggesting that glial cells may mediate estrogen-positive feedback. These data indicate that, absent the peripheral steroidogenic tissues, estrogen can induce progesterone dependent events by stimulating the synthesis of neurosteroidal progesterone. We propose to test the hypothesis: estrogen stimulates synthesis of hypothalamic progesterone that activates circuits regulating the LH surge and sexual behavior. Three experiments are proposed: First, using intact and ovx/adx rat models we will directly test whether the estrogen-induced LH surge is dependent on increased hypothalamic neurosteroidal progesterone. Second, we propose to determine whether estrogen increases the expression and/or activity of steroidogenic enzymes (P450 side chain cleavage and 3beta-HSD) needed to synthesize progesterone, in vitro and in vivo. Third, using the same intact and ovx/adx rat models, we will determine whether estrogen-induced hypothalamic progesterone is sufficient to facilitate sexual behavior. These studies will demonstrate the physiology of neurosteroidal progesterone and provide important new information about the mechanism of estrogen-positive feedback in the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTERONE /MELATONIN AS NEUROPROTECTANTS IN NERVE INJ Principal Investigator & Institution: Yu, Wan-Hua A.; City College of New York 138Th St and Convent Ave New York, Ny 10031 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: Motor neurons of adult animals, despite resistance to axotomy-induced cell death, undergo apoptotic cell death after nerve injury with removal of axon associated Schwann cells, indicating that neurotrophic factors from central glial cells may not be adequate to support the survival of injured neurons. This proposal aims to test the hypothesis that glial synthesis of neurotrophic factors can be up-regulated by steroid hormones, and that death of injured neurons is preventable by agents which scavenge free radicals and remove reactive oxygen species. Adult rat hypoglossal nerve innervating the tongue muscles will be lesioned on one side by crush (for reversible injury), ligation (to permanently disconnect neurons from target muscles but retain the proximal nerve segment), and avulsion (to deprive neurons of Schwann cell-derived neurotrophic factors). The vagus nerve will be crushed or transected to include parasympathetic motor neurons for comparison. Since progesterone (PG) and melatonin (MT) possess antioxidant activities; and in cerebral ischemia and truamatic injuries, reduce tissue damage, attenuate brain edema and cell loss, and facilitate functional recovery; and glial cells have PG receptors, nerve lesioned rats will receive PG injection daily via s.c. route, MT by osmotic pump infusion, combined treatment of the two agents, PG antagonist RU486 to block endogenous PG activities, and no treatment as control. Specific questions to be addressed are: (1) Will PG increase the synthesis of brain-derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF)? (2) Will PG and MT prevent the loss of neurons after nerve avulsion? (3) What is the status of PG receptors in motor neurons before and after axotomy? Will PG affect the expression of PG receptors ininjured neurons? (4) Will a "death receptor" FAS be induced in neurons after nerve avulsion? Will PG and MT block the induction or reduce
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39
the expression of FAS and p75 in injured neurons? To answer these questions, tissue sections will be prepared for neuronal cell counting, and for immunostaining of BDNF, GDNF, PG receptors, FAS and p75, and quantify their levels by computerized image analysis. These studies will provide insight into the cellular and molecular events responsible for the initiation and activation of apoptotic pathways in injured neurons, and offer therapeutic potential for treating traumatic injuries and other neuropathological conditions. 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 2001; 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. 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
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Project Title: PROGESTERONE AND SLEEP IN OLDER WOMEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004
40
Progesterone
Summary: Sleep complaints increase significantly with age in women. Many older women experience difficulty falling asleep, more night-time awakenings, and less restful sleep. Sleep studies verify that disturbed sleep patterns are observed even in healthy older women. Sleep disturbances are associated with increased daytime drowsiness, increased accident risk, increased use of health care, and reduced quality of life. Older women receive a disproportionate number of sedative-hypnotic medications, which can exacerbate sleep apnea and have daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be menopause-related changes in sex steroids such as estrogen and progesterone. Research attention has focused on estrogen. However, progesterone may also participate in the control of sleep. Clinical reports indicate that women often feel drowsy after they take oral progesterone - an effect which is undesirable during the day, but may be positive at night. To date there are no published studies of progesterone's effect on the objectivelymeasured sleep and daytime drowsiness of older women. The proposed study will take a systematic, multi-dimensional approach to determining the effect of progesterone on the sleep and drowsiness of older women. Objective techniques (polysomnography, Multiple Sleep Latency Test) will be used to measure sleep and daytime drowsiness following evening or morning administration of 300 mg micronized progesterone, in 40 postmenopausal women who are at least 5 years past menopause and who are not experiencing hot flashes. Attention, memory, subjective sleepiness, and blood levels of progesterone and its metabolite (allopregnanolone) will also be measured. This study is part of a long-term research plan to assess (1) how the very low postmenopausal levels of estrogen and progesterone contribute to sleep difficulties of older women, and (2) how hormone replacement therapy affects the sleep of women. An ongoing placebocontrolled study is investigating the effects of estrogen on the sleep of older women. The proposed study will complement the estrogen study. It will enhance our limited understanding of the relationship between sex steroids and sleep, and the factors that contribute to sleep problems in older women. 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,
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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 RECEPTOR AND BREAST CANCER Principal Investigator & Institution: Lydon, John P.; Cell Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Breast cancer is recognized as the most prevalent malignancy among women in North America with a life time risk currently estimated to be one in eight. Most importantly, reproductive history or more specifically steroid hormonal status has been shown to be an important risk factor. Recently, I generated a progesterone receptor (PR) knockout (PRKO) mouse that has demonstrated that progesterone (P), and its receptor, the PR, are absolutely required for normal mammary gland proliferation and differentiation. The involvement of P in mammary tumorigenesis has been a matter of controversy for several years mainly because P can protentiate or inhibit mammary tumorigenesis. To clarify the complex temporal relationship between P and mammary tumorigenesis, the PRKO mouse will be utilized to determine whether the P induedproliferative signal has a role to play in breast cancer by investigating the effects of removing PR function on mammary tumor progression. The specific aims of this proposal are to: 1) evaluate whether removal of PR function alters murine susceptibility to carcinogen-induced mammary tumorigenesis at the morphological, histological, and molecular level; 2) determine whether PR function has a role in the development of hormone dependent mammary tumors exhibited by the Grunder mouse and define whether the PR has an involvement in the progression of these tumors to a hormone independent phenotype; and 3) to define the distinct effects of mammary epithelial and stromal derived PR populations on mammary development and tumorigenesis by using reciprocal mammary gland transplantation technology. Apart from advancing our current understanding of P's contribution to mammary tumorigenesis, information from these studies will aid in the design of effective strategies for breast cancer prevention and treatment as well as prompting a reevaluation of the current use of progestins in contraception and postmenopausal hormonal replacement therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
42
Progesterone
•
Project Title: PROGESTERONE RECEPTOR AND THE HSP90 CHAPERONE PATHWAY Principal Investigator & Institution: Toft, David O.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Progesterone receptor and the hsp90 chaperone pathway. When in its inactive form in cytosol extracts, the avian progesterone receptor (PR), like most steroid receptors and several other cell signaling proteins, is complexed with the heat shock protein hsp90. This complex does not form through a simple association, but through a process that requires ATP hydrolysis and several additional proteins. Other proteins involved in receptor complex formation are hsp70, three hsp70 co-chaperones, hsp40, Hip and Hop, four hsp90-binding TPR proteins and p23. We have developed a chemically defined system with purified proteins that has the capacity to assemble PR complexes with hsp90. Only five of the above proteins are needed for this in vitro assembly process which appears to proceed through three steps to generate PR with hormone binding activity. The objective of the proposed studies is to further our understanding on the assembly of receptor complexes, their dissociation upon hormone binding, and the functional significance of the receptor-associated proteins. This will be accomplished by extensive use of the in vitro defined assembly system. Events at each step of PR complex formation will be characterized in terms of the dynamics of protein interactions and the utilization of ATP. Modifications in the system will be made that allow the study of hormone- dependent dissociation of PR from hsp90. This will probably require the identification of new factors needed for the dissociation process. Finally, we will characterize the domains or elements of the PR that are interaction sites for binding hsp70 and hsp90 and investigate the properties which promote heat shock protein recognition. These studies should lead toward a mechanistic description of the steroid receptor activation process and should provide valuable information for understanding the mechanisms of action of the molecular chaperones hsp70 and hsp90. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTION
PROGESTERONE
REGULATION
OF
GRANULOSA
CELL
Principal Investigator & Institution: Peluso, John J.; Professor of Physiology and Ob/Gyn; Obstetrics and Gynecology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: The overall goal of this proposal is to test the hypothesis that progesterone regulates granulosa cell (GC) function by activating a membrane receptor that has some GABAA receptor features. We have recently shown that progesterone's anti-apoptotic and anti-mitotic actions are attenuated by the GABA antagonist, bicuculline. Further, progesterone's actions can be attenuated by an antibody directed against the ligand binding domain of the nuclear progesterone receptor. When used in a western blot analysis, this antibody recognizes a 60 kDa protein within ovarian and GC lysates. This 60 kDa protein is also detected within membrane preparations of ovarian lysates. Finally, the progesterone receptor antibody detects a 60 kDa protein after immunoprecipitation with an antibody against the GABAA receptor. These findings support our hypothesis that progesterone mediates its actions within the ovary through a membrane-type receptor that has a molecular weight of approximately 60 kDa and has some pharmacological and immunological characteristics of a GABAA-receptor. In this
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proposal we will directly test this hypothesis through a series of experiments which use 1) pharmacological agents to define progesterone's function, 2) competitive progesterone assays and scatchard plot analysis to assess the specificity of progesterone binding to GCs, 3) western blot and immunocytochemistry to detect the expression pattern of this putative 60 kDa membrane progesterone receptor during follicular growth, differentiation and atresia. It is proposed that progesterone acts through this putative 60 kDa membrane progesterone receptor to regulate both GC mitosis and viability within the preovulatory follicle. The concept is in marked contrast to the traditional view that progesterone's biological actions are almost exclusively restricted to non-ovarian tissues. Therefore, the proposed studies will provide new and important insights into the cellular mechanisms through which progesterone regulates GC function. Further characterization of this ovarian mechanism could ultimately lead to the development of antagonist and/or agonist which specifically modify progesterone's actions within the ovary without altering its genomic action within non-ovarian target cells. As such, these putative antagonists/agonist could find applications in the treatment of ovarian cancers, infertility and premature ovarian failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTERONE TREATMENT OF BLUNT TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Kellermann, Arthur L.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: Traumatic brain injury (TBI) is a major cause of premature death and disability worldwide. Few effective treatments exist. Based on encouraging results from studies with animals, we hypothesize that early administration of progesterone to victims of moderate to severe TBI reduces secondary brain injury and improves neurological outcomes. Prior to proceeding with a full-scale clinical trial, we propose to conduct a pilot study by identifying and recruiting eligible subjects at a single level I trauma center. Consenting subjects will be randomly assigned to receive either IV infusion of progesterone or an equivalent volume of placebo. The study team, which will be blinded to treatment status, will monitor each subject's clinical progress and assess outcome at one month post-injury. The primary objectives of this pilot study are to: 1) achieve proper dosing of the study drug, 2) gather data on drug safety, and 3) generate preliminary evidence of efficacy. The secondary objective is to identify the most appropriate clinical subgroup(s) for subsequent treatment in a multi-center trial. To identify the correct dosage and infusion rate to achieve a steady state serum progesterone concentration (SSSPC) level of 450 nmole/L + 100 in our subjects, we will statistically examine the SSSPCs of the first ten subjects randomized to progesterone. To test the safety of the progesterone infusion, we will monitor patients for several unlikely, but potential complications of progesterone administration. To assess the potential efficacy of the progesterone for TBI, we will compare treatment groups with respect to duration of coma, death at one month post-injury, and most important, neurological outcome at one month post-injury. Three measures of neurological outcome will be used: the Glasgow Outcome Score, the Disability Rating Scale, and the Galveston Orientation and Amnesia Test. Once these objectives are accomplished, we will apply the lessons learned in this pilot study to mount a multi-center, randomized, double blind, placebo-controlled clinical trial of intravenous progesterone for treatment of traumatic brain injury. If the therapeutic benefits observed in animals are replicated in humans, administration of intravenous progesterone should produce several benefits,
44
Progesterone
including: a) decreased duration of coma; b) decreased mortality; and c) improved neurological function. If these hypotheses are verified, this it will represent a major advance in the treatment of traumatic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTERONE, CELL CYCLE AND CANCER Principal Investigator & Institution: Pollard, Jeffrey W.; Professor; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 05-JAN-2001; Project End 31-DEC-2005 Summary: Estrogens are the major carcinogen in the environment of most females with exposure to unopposed estrogen increasing the risk of breast and endometrial cancer. Conversely, it has become increasingly apparent that estrogens are essential for the well being of women (and men) throughout life. Progesterone acts to oppose the effects of estrogen on cell proliferation and, consequently, it is used in the treatment of endometrial cancer and it is an essential component of hormone replacement therapy designed to alleviate post-menopausal symptoms in women. It is, therefore, of fundamental importance to understand the mechanism of action of these hormones on cell proliferation. In adult ovariectomized mice, a single injection of estradiol-17beta (E2) results in the stimulation of a wave of DNA synthesis and cell proliferation that is restricted to the uterine epithelium. This proliferation is completely inhibited by pretreatment with progesterone (P4). The uterine epithelium can be isolated with great purity in a state suitable for biochemical analysis. This method together with defined hormonal regimens provides a controllable model in which to study the mechanism of action of these hormones in vivo. In tissue culture cells the cell cycle is regulated by the orderly activation of cyclins and their dependent kinases (Cdk). These include the cyclin D-Cdk4 and cyclin D-Cdk6 complexes acting early in G1 and the cyclin E-Cdk2 complex acting at the G1 to S-phase boundary. Our studies in the uterine epithelium have shown that E2 induces the re-localization of cyclin D1 and Cdk-4 to the nucleus and, results in orderly activation of cyclin-E and cyclin ACdk-2 activities and hyper-phosphorylation of pRb and p107. Progesterone pre- treatment prohibited the cyclin D1/Cdk-4 relocalization to the nucleus with a consequent inhibition of pRb and p107 phosphorylation. In addition, P4 abrogated the E2 induced cyclin E and cyclin A-Cdk2 activities. The specific aims of this grant are: 1) To determine the mechanism whereby P4 prohibits cyclin D1/Cdk4 nuclear accumulation following E2 treatment; 2) To determine the mechanism of action of P4-inhibition of Cdk-2 activation; 3) identify differentially regulated genes in the uterine epithelium following E2 treatment in the presence and absence of P4; 4) to develop methods to interfere with signaling pathways in the uterine epithelium in vivo. It is expected that by the end of the grant that the mechanisms of cyclin D1/Cdk4 exclusion can be identified and novel proteins associated with this process isolated. Furthermore, novel E2 and P4-regulated genes that play important roles in the control of epithelial cell proliferation should be identified. These studies will define specific mechanisms that may result in the development of therapeutics that would inhibit estrogen's mitogenic effects in tumors as well as in benign proliferative diseases such as endometrial polyps and endometriosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGESTERONE/ANDROGEN FEEDBACK CONTROL OF GNRH NEURONS Principal Investigator & Institution: Moenter, Suzanne M.; Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904
Studies
45
Timing: Fiscal Year 2003; Project Start 23-APR-2003; Project End 31-MAR-2008 Summary: Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway regulating reproduction. Pulsatile release of GnRH stimulates secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from pituitary gonadotropes and is absolutely required for fertility. In female mammals, shifts in GnRH pulse frequencies help drive the preferential release of LH or FSH at specific times of the cycle to create appropriate hormone milieux for ovarian follicle maturation. GnRH pulse patterns are largely regulated by negative feedback from the ovarian steroids progesterone and estradiol. Although this feedback is well characterized in vivo, the underlying cellular mechanisms and neural pathways have yet to be elucidated. This has precluded understanding the neural components of common forms of hypothalamic infertility, such as polycystic ovarian syndrome (PCOS), in which elevated circulating androgen levels are accompanied by a persistent high frequency of LH (and presumably GnRH) release. The latter appears to be due in part to androgens interfering with the efficacy of progesterone feedback. Considerable evidence suggests one mechanism of steroid feedback regulation of GnRH release is transsynaptic. In particular, anatomical and physiological data support a role for gamma-aminobutyric acid (GABA)- and opiate peptide-producing neurons in this communication. Four Specific Aims are proposed to investigate the cellular mechanisms of progesterone feedback, and how androgens might alter the efficacy of progesterone feedback. The primary methodology will be electrophysiological recordings of green-fluorescent protein-identified GnRH neurons in acute brain slices. Aim 1 will investigate the effects of steroid and neurotransmitter milieux on the firing properties and firing patterns of GnRH neurons. Aim 2 will examine how steroids and neurotransmitters alter GABAergic drive to GnRH neurons. Aims 3 and 4 will study the effects of steroids and neurotransmitters on potassium and calcium currents, respectively, as these play major roles in setting firing properties of neurons as well as their ability to respond to synaptic input. These studies will help us understand GnRH neuron physiology in both healthy and diseased states, knowledge paramount for improving treatments for hypothalamic fertility disorders, developing novel contraceptive methods, ensuring effective reproduction in endangered and food-producing species, and understanding other similar neuronal systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTIN AND GROWTH FACTOR CROSS-TALK IN BREAST CANCER Principal Investigator & Institution: Lange, Carol A.; Associate Professor; None; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 22-SEP-1997; Project End 31-JUL-2005 Summary: (provided by applicant): The ovarian steroid hormones, estrogen and progesterone, promote accumulation of genetic changes during the development of breast cancers, and drive the growth of established breast cancer. During late stages of breast cancer progression, tumors usually become steroid hormone resistant and concurrent amplification of type I (EGFR/c-erbB2) tyrosine kinase growth factor receptors occurs with high frequency; these alterations are associated with a particularly poor prognosis. EGF/erbB2 receptor signalling initiates cytoplasmic protein kinase phosphorylation events that are part of the mitogen-activated protein (MAP) kinase cascade. Endpoints of MAPK signalling include activation of transcription factors that control the expression of genes involved in cell growth regulation. In breast cancer cells, EGFR and c-erbB2 receptors are regulated by steroid hormones, and cross-talk between
46
Progesterone
these pathways is becoming well-established. Phosphorylation of progesterone receptors (PR) by MAPK is required for ligand-dependent downregulation by the ubiquitin-proteasome pathway. Paradoxically, this same event mediates nuclear association of PR and greatly potentiates PR transcriptional activity. Our preliminary data show that growth factors are key regulators of steroid hormone sensitivity. We postulate that growth factors drive breast cancer cell growth in part by "de-repressing" steroid hormone receptor function. This involves regulatory interplay between receptor phosphorylation, ubiquitination, and sumoylation. The specific aims in this proposal will address the following questions: 1) Which kinase pathways input to PR regulation? 2) What is the basis for the inverse relationship between PR stability and transcriptional activity? And 3) What is the functional significance of PR sumoylation in response to growth factor and steroid hormone signalling? These aims will define the molecular mechanisms of growth factor regulation of PR function in breast cancer cells. The longterm goal is to define the role of growth factor signalling in the progression of breast cancer cells towards steroid hormone resistance. If we can understand the mechanisms that control this switch from growth stimulation by steroid hormones to growth factors, this pathway could, in theory be blocked, which would lead to longer disease-free survival of patients with breast cancer. This work will aid our understanding of how steroid hormone resistance develops, and will identify new therapeutic targets for breast cancer treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROGESTOGENS VS PHYTOESTROGENS-- AN ADJUNCT TO ERT Principal Investigator & Institution: Williams, James K.; Associate Professor; Pathology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 20-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) There is now a consensus that postmenopausal estrogen replacement therapy (ERT) reduces morbidity and mortality from coronary heart disease (CHD). However, there is a continuing concern that the concurrent use of a progestogen (HRT) to protect the endometrium may reduce the cardiovascular benefits of ERT. This has stimulated interest in developing cardiovascular-safe (CV-safe) progestogens and/or alternative approaches to protect the endometrium and breast during estrogen replacement therapy. Progesterone does not diminish the cardiovascular benefits of ERT. However, it provides little or no additional beneficial effects on CV-risk, is associated with continued menstrual cycles and is not protective for the breast. Soy phytoestrogens (SPEs) may be an effective alternative approach to progestogen therapy. We have shown that SPEs have estrogen agonist effects on the cardiovascular system, but antagonizes the effects of ERT on mammary and endometrial tissue. Furthermore, SPEs combine with ERT to have additive beneficial effects on the cardiovascular system and on preservation of bone density. Thus, we hypothesize that, because of their estrogen agonist/antagonist properties, SPEs can obviate the need for progestogen therapy during ERT of postmenopausal females. To this end, our specific aims are: 1) To assess the potential contribution of increasing doses of SPEs to the putative beneficial cardiovascular (plasma lipoprotein concentrations, carbohydrate metabolism, vascular reactivity, hemodynamics) and bone (plasma markers of bone metabolism) effects of ERT treatment in postmenopausal subjects; 2) To identify the dose of SPEs that protects the mammary and endometrial tissue from ERT-induced cell proliferation and hyperplasia; 3) To identify and compare the potential additive beneficial effects of SPEs with those of progestogen treatment (MPA or progesterone) on cardiovascular and bone endpoints in postmenopausal
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subjects receiving ERT; and 4) To measure and compare the effects of SPE administration with those of MPA and progesterone, on mammary and endometrial hyperplasia in postmenopausal subjects receiving ERT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSTAGLANDINS IN PRIMATE OVULATORY FOLLICLES Principal Investigator & Institution: Duffy, Diane M.; Physiological Sciences; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-AUG-2004 Summary: Preliminary studies conducted by the PI indicate that the ovulatory gonadotropin surge initiates prostaglandin (PG) production by the primate periovulatory follicle and the injection of a PG synthesis inhibitor directly into the follicle prevents follicle rupture without altering normal luteal progression. The proposed studies will address the hypothesis that PGs produced by the preovulatory follicle act locally to regulate specific molecular events related to follicular rupture, but not luteinization, of the primate follicle. Experiments are proposed to examine the locations and gonadotropin regulation of PG synthetic enzymes within the primate periovulatory follicle (Specific Aim 1). In vitro protocols will be used to determine if gonadotropin stimulation of granulosa and/or theca cells of the follicle is sufficient to initiate PG synthesis (Specific Aim 2). PG receptors will be localized to cells of the periovulatory follicle to determine the site(s) of PG action (specific Aim 3). PGstimulated expression of molecular markers of follicle rupture (matrix metalloproteinases and their inhibitors [TIMPs], plasminogen activator and its inhibitor and luteinization (3beta hydroxydehydrogenase, steroidogenic acute regulatory protein [STAR], vascular endothelial growth factor (VEGF], angiopoietin-1 and 2) will be assessed (specific Aim 4). Immunocytochemistry and in situ hybridization will be used to localize PG synthetic enzymes and PG receptors to the cells of the preovulatory follicle. Gonadotropin regulation of mRNAs for PG synthetic enzymes will be determined by semi-quantitative RT-PCR based assays. PG production of cultured ovarian cells and tissues will be measured using EIA kits. In vitro expression of markers of follicular rupture/luteinization will be assessed using RT-PCR based assays for mRNAs, ELISA kits for enzyme proteins and angiogenic factors, and RIA for media progesterone. Intrafollicular injection of PG synthesis inhibitor will be used to determine if PGs regulate specific markers of follicular rupture and luteinization in vivo. These studies will likely demonstrate that the mid cycle gonadotropin surge initiates PG synthesis by primate ovarian follicle through the induction of specific enzymes and support the hypothesis that PGs act locally to trigger specific processes related to ovulation, but not luteinization, of the periovulatory follicle. This may provide insight into the mechanisms leading to infertility (e.g., leuteinized unruptured follice syndrome) and support the developoment of PG synthesis inhibitors of PG synthesis inhibitors for use as contraceptives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION PHOSPHORYLATION
OF
HUMAN
STEROID
RECEPTORS
BY
Principal Investigator & Institution: Weigel, Nancy; Associate Professor; Cell Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 15-APR-1993; Project End 31-MAR-2005
48
Progesterone
Summary: The activities of steroid receptors (SR) are regulated both by hormones and by alterations in cell signaling pathways. Our goal is to understand how phosphorylation regulates the activity of the human progesterone receptor (PR) :Specific Aim #l: To utilize state of the art, high sensitivity mass spectrometry to identify additional phosphorylation sites and/or other post- translational modifications in PR. Specific Aim #2. To develop and characterize novel phosphorylation site-specific antibodies for analysis of the role of phosphorylation in receptor structure and function. We have already produced two phosphorylation site-specific antibodies and applied them to an analysis of cross-talk with PR. These antibodies and the new ones to be made in this aim will permit uniquely powerful approaches to studying regulation of PR phosphorylation. Specific Aim #3: To assess the role of phosphorylation in specific receptor functions. We will test our hypothesis that two important functions of PR phosphorylation are l: to regulate transcriptional activity through modulation of protein/protein interactions (both intramolecular and intermolecular) and 2: to regulate receptor turnover. Specific Aim #4: To examine the hypothesis that an additional important function for phosphorylation is to integrate PR with other signaling pathways, we will use novel phosphorylation site specific antibodies as probes for specific phosphorylations, we will elucidate the cell signaling pathways that regulate PR phosphorylation and activity. Modulation of cell signaling pathways alters PR activity and can even cause antagonists to act as agonists, but the pathways and mechanisms by which this occurs are not well understood. We will use the phosphorylation site specific antibodies as an aid in defining the pathways and kinases responsible for specific phosphorylations, leading to altered receptor activation and to examine cell cycle effects on receptor phosphorylation and function. Understanding the interplay between steroid receptors and cell signaling pathways will aid in understanding the normal actions of agonists and antagonists as well as the changes that occur in diseases such as hormone dependent cancer where cell signaling is altered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION MYOMETRIUM
OF
PROSTAGLANDIN
RECEPTORS
IN
Principal Investigator & Institution: Myatt, Leslie; Professor; Obstetrics and Gynecology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Prostaglandin's (PG's) produced by intrauterine tissues appear to have a major role in the initiation and/or maintenance of parturition. The response and sensitivity of myometrium to PG's may be governed by differential expression of various PG receptors which are part of the superfamily of G protein coupled receptors that have seven transmembrane spanning domains. The response to any particular prostaglandin (e.g. PGE2) may depend on the receptor isoforms and their subtypes expressed at any particular time. Currently there is no comprehensive data on expression of PG receptors in the pregnant myometrium or their hormonal regulation. It is also currently suggested that the pregnant human uterus may show a functional regionalization at term whereby the lower segment relaxes to allow passage of the fetal head, but the upper segment contracts to expel the fetus. This regionalization may be mediated via differential expression of PG receptor isoforms. The cloning and sequencing of these receptors offers the opportunity to study isoforms and subtypes present, their ontongeny throughout gestation and changes with parturition and hormonal manipulation. The overall hypothesis to be tested is that uterine responsivity to prostaglandins is in part regulated by differential expression of contractile and
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49
relaxatory PG receptor isoforms in myometrium and that this expression is hormonally regulated in part by estrogen/progesterone. The objectives of the study are (1) to study mRNA and protein expression and localization for contractile FPI, EP1, EP3, and TP and relaxatory IP, EP2, and EP4 receptors in pregnant rat myometrium (day 16 to one day postpartum) and in pregnant animals with hormonal manipulation to alter the endocrine (estrogen/progesterone) milieu at term (day 16 onwards) (2) to study expression and localization of contractile and relaxatory PG receptors in paired upper and lower segment pregnant human myometrial samples obtained either at term or preterm from patients who are or are not in labor (3) to study the cellular localization of PG receptors in myometrium using confocal microscopy on tissue sections and isolated myocytes (4) to determine the response elements in the 5' flanking region of the EP2 gene that determine alterations in expression at term. These studies will provide a comprehensive picture of which receptors are expressed in myometrium, how the expression changes with gestation and the onset of labor and the effect of estrogen/progesterone on this expression. The human studies will also reveal if there is a functional compartmentalization in human myometrium associated with differential expression of PG receptors. The confocal microscopy will provide information on cellular localization of receptors and the promoter analyses will reveal potential regulatory sites for control of expression of uterine receptors at parturition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF PROSTAGLANDINS IN PERIOVULATORY FOLLICLES Principal Investigator & Institution: Fortune, Joanne E.; Biomedical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: (provided by applicant): The LH/FSH surge sets in motion a cascade of events that culminates in the remarkable rupture of the follicular wall at the apex and the subsequent release of the oocyte-cumulus complex. Despite its critical importance to reproduction and fertility, and despite decades of research, there are many gaps in our knowledge of the regulation of the ovulatory process. Many regulators and pathways have been hypothesized to be involved in mammalian ovulation, but results of previous studies have highlighted essential roles for progesterone and prostaglandins (PGs). Cattle provide an ideal animal model for studying the complex events of the periovulatory period. We have validated a model for inducing periovulatory follicular development in cattle and we now propose to use it to test hypotheses about these two key regulators of ovulation and their receptors. In Specific Aims 1 and 2, the timing, cellular site(s) of synthesis, biosynthetic pathway, and hormonal regulation of the periovulatory increase in PG synthesis will be examined. The hypothesis to be tested is that both theca and granulosa cells respond to the preovulatory LH/FSH surge with an increase in PG production, mediated by the surge-induced rise in progesterone, which in turn induces PGF2a synthesis, via reduction from PGE2. In Specific Aim 3 we will test the hypothesis that the effects of progesterone on prostaglandin production by the periovulatory follicle are at least partially mediated through progesterone-induced increases in oxytocin. Although PGs are essential for ovulation, virtually nothing is known about the expression of PG receptors during the periovulatory period. In Specific Aim 4, the temporal expression of mRNA for PGF2alpha receptor in bovine periovulatory follicles will be determined. The hypothesis that mRNA for the receptor is expressed coordinately with the rise in PG synthesis and, is localized to the theca cells of the periovulatory follicle will be tested. Specific Aim 5 is designed to test the hypothesis
50
Progesterone
that the LWFSH surge induces progesterone receptor (PR) in follicular cells of the periovulatory follicle and that these receptors mediate progesterone's effects on PG production. Together these experiments will provide new knowledge about the regulation of, and relationship between, these two essential mediators of ovulation and their receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF RENIN AND PREECLAMPTIC HYPERTENSION Principal Investigator & Institution: Shah, Dinesh M.; Professor; Reproductive Biology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 19-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Many tissues secrete an inactive pro-form of renin. A 43 amino acid pro- segment removal to produce active renin is believed to occur, primarily in the kidney. Recent data on transgenic mouse model of preeclampsia support a role of reproductive renin in its pathogenesis and our data on increased decidual renin expression in human preeclampsia confirms this role. For renin to have such a functional role, cellular processing to active renin should occur locally. The cellular and molecular aspects of the uterine renin- angiotensin system have not been adequately investigated. Presence of estrogen and progesterone response elements in the promoter of renin gene suggests a role for the sex steroids in the regulation of prorenin expression. Our recent data suggest that progesterone treatment of endometrial stromal cells (in vitro decidualization) increases active renin secretion by increasing prorenin expression and by increasing conversion of prorenin to renin in a hormone- specific manner, and that decidual cells from human gestation process prorenin to renin. Our most recent co-transfection experiment in HEK293 cells and cathepsin B inhibition in decidual cells suggest that cathepsin B may function as a prorenin convertase. We hypothesize that pathologic increase in decidual renin may proximately initiate preeclampsia, and sex steroids may induce expression of prorenin and its proconvertase (PC), thereby regulating mature renin secretion. Therefore, the objectives are: 1) To demonstrate that decidual stromal cells in vitro secrete active mature renin, as assayed by activity and by N terminal sequencing; 2) To identify the decidual cell endoprotease responsible for prorenin activation by (i) northern analysis with probes for PCs and cathepsin B, and (ii) defining constitutive versus regulated renin secretion, and (iii) examining the effect of cathepsin B inhibition on prorenin processing; (b) To examine regulation of endoprotease expression; 3) To confirm that the candidate-activating enzyme is the specific prorenin convertase by (a) immunomicroscopic co-localization with prorenin in the vesicles and (b) functional verification by co-transfection of prorenin and candidate-activating enzyme expression vectors in a standard cell line and demonstration of processing to mature active renin. These studies will improve our understanding of the role of progesterone in the regulation of reproductive renin and may provide a novel direction for investigating the pathophysiology of preeclampsia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF UTERINE SMOOTH MUSCLE EXCITABILITY Principal Investigator & Institution: Davy, Kevin P.; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004
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Summary: Preterm births account for only 10 percent of all deliveries, but are associated with over 80 percent of newborn deaths and more than 95 percent of major newborn morbidity. The lack of understanding of the mechansims regulating uterine contraction has hampered progress towards an effective treatment for this reproductive health problem. Currently used tocolytics have little effect in prolonging gestation, necessitating the investigation of other mechansims of prevention. One potential class of therapeutic targets is potassium channels, due to their ability to potently buffer cell excitation. Electrophysiological reports have shown that myometrial cells contain a variety of K+ channel types that may be potential therapeuric targets, including the large-conductance calcium-activated K+ channel (BKCa channel). Blockage of BKCa channels depolarizes myometrial cells and increases contractile activity while activation of these channels by agonists and beta-adrenergic agents induces potent uterine relaxation. Interestingly, the activation of the BKCa channel by phosphorylating agents, Ca2+, or voltage is dependent on whether it is isolated from non-pregnant or pregnant tissue. Recent evidence illustrates the ability of this channel to undergo alternative splicing in the presence of stress hormones, yielding variants that differ in their sensitivity to intracellular Ca2+ and voltage. Sensitivity to these agents is also dependent on the association of the BKCa channel with its ancillary beta subunit. This suggests that alternative splicing or modulation of beta subunit association may be mechanisms regulating BKCa channel diversity in uterine smooth muscle during gestation. While this channel appears to be an important regulatory component of uterine excitability, its role in modulating myometrial contraction during gestation remains unknown. The specific objective of this proposal is to detemine whether modulation of BKCa channel splice variant expression or beta subunit association correlates to a functional difference in uterine excitability during gestation. Alterations in BKCa channel splice variant expression and function during gestation will be investigated by molecular charactization in combination with electrophysiological and contraction measurements in mice. The specific aims of this proposal are to: 1) compare transcript and protein expression patterns of BKCa channel isoforms in mouse uterine smooth muscle during gestaiton, 2) elucidate BKCa channel beta subunit transcript and protein expression during gestation and detemine whether its assembly with the alpha subunit is modulated during pregnancy, 3) determine the contribution of BKCa channel splice variants to the regulation of uterine smooth muscle contraction during gestation, and 4) characterize the expression of the splice variants of the BKCa channel alpha subunit following stimulation with estrogen and progesterone. Preterm labor is a major health problem, especially given the risks it carries with respect to birth defects and the costs associated with premature delivery. Whether the BKCa channel could be a future target for tocolytic drug therapy is thus a significant question to examine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF VASCULAR FUNCTION BY PROGESTERONE RECEPTOR Principal Investigator & Institution: Iruela-Arispe, Luisa; Professor; Molecular, Cellular & Dev Biol; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 13-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): ln addition to its role in the physiology of the female reproductive tract, progesterone also impacts the cardiovascular system. Nonetheless, the specific effects of this steroid hormone in blood vessels remain unclear. The recent generation of mouse models that lack progesterone receptor (PR) have confirmed that
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vascular function is affected by progesterone, yet a deeper understanding is still lagging and urgently needed considering the questionable effect of hormonal replacement therapy in the amelioration of cardiovascular disease. Using an animal that expresses beta-galactosidase in the PR locus (PRknock-in beta gal) we found that this gene is expressed in both smooth and endothelial cells providing a rationale to pursue a detailed evaluation of PR function in blood vessels. To gain further insight on the role of PR signaling in the vasculature, we generated a transgenic mouse that over and missexpresses PR in the endothelium of several vascular beds. Systemic treatment with progesterone resulted in pathological vascular permeability in the subset of organs that expressed the transgene. This unexpected finding was in accordance with some phenotypic aspects of the PRKO mouse, which failed to mount an endometrial decidual response upon stimulation with hormones. The decidual response includes concrete alterations in endometrial glands, stromal differentiation, and vascular permeability. Further investigation using endothelial cultures revealed that PR promotes fundamental changes in inter-endothelial junctional complexes. The signaling events mediated by PR appear to be non-genomic in nature and dependent, at least partially, on the ability of PR to directly activate src. In this application, we propose three aims to directly test the hypotheses that progesterone receptor signaling on endothelial cells mediates vascular permeability and formation of intercellular gaps. Specifically we will: (1) Further characterize the effect of progesterone receptor activation on endothelial cells; (2) investigate the molecular mechanisms that mediate progesterone-induced vascular permeability; and (3) determine the biological significance of progesterone receptor signaling in the endothelium and smooth muscle using cell-specific gene ablation. We believe that further elucidation of the role of PR on blood vessels is long overdue and required to gain a concrete understanding of the physiological and pathological effects of this hormone in the cardiovascular system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATORY ROLES OF PNRC IN BREAST EPITHELIAL CELLS Principal Investigator & Institution: Chen, Shiuan; Professor & Director; City of Hope National Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: This proposed investigation will test the hypothesis that, together with Grb2 (Growth factor receptor bound protein- 2), PNRC (Proline-rich Nuclear Receptor Coregulatory protein) modulates both the nuclear receptor-mediated regulation and the growth factor/Ras mediated regulation in human breast epithelial cells. PNRC was identified in a yeast two-hybrid screening of a human mammary gland cDNA expression library by using bovine SF1 (Steroidogenic Factor 1) as bait. Three important sets of results have been generated in our laboratory. First, by using RT-PCR, PNRC was found to be selectively expressed in breast epithelial cells, and the expression levels in non-cancerous cell lines were found to be higher than those in breast cancer cell lines. Second, PNRC was shown to act as a coactivator for nuclear receptors such as ER (estrogen receptor) and PR (progesterone receptor). The coactivator activity can be suppressed by Grb2. Third, by interacting with Grb2, PNRC suppresses growth factorinduced MAP (mitogen-activated protein) kinase activation. There are five specific aims in this proposal. Aim 1 will study the function of PNRC by stable transfection experiments. Aim 2 will study the dynamics of intracellular movement of PNRC and Grb2 with experiments using transfected fluorescent protein (FP)-PNRC and FP-Grb2 fusion proteins. Aim 3 will determine the molecular basis of the interaction between PNRC and nuclear receptors by protein deletion and site-directed mutagenesis
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experiments. Aim 4 will determine the molecular basis of the interaction between PNRC and Grb2. Aim 5 will apply the yeast two-hybrid screening method to identify protein(s) in human breast tissue that interacts with PNRC. These experiments will determine the molecular basis of the interaction between PNRC (PNRC2) and Grb2, examine the functions of these proteins on the nuclear receptor-mediated pathway and the growth factor-mediated pathway in human breast, and identify additional molecules in breast tissue that interact with PNRC. This laboratory is familiar with all the experimental techniques proposed in this application. Both the nuclear receptor-signaling pathway and the growth factor-signaling pathway have been extensively studied, and the control mechanisms for these pathways are complex. However, the findings on PNRC and Grb2 represent a newly identified mechanism for modulating these pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRODUCTIVE HORMONES: BIOLOGICAL AND MOLECULAR ACTIONS Principal Investigator & Institution: O'malley, Bert; Professor and Chairman; Cell Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-SEP-1974; Project End 31-MAY-2003 Summary: The steroid hormones (estrogen and progesterone) stimulate growth, maturation and the development of new biochemical capacities in their endocrine target organs. Although it is widely accepted that steroid hormones exert major influences on the transcriptional process, the detailed mechanisms and the associated co-regulator proteins involved in gene transactivation are not yet defined in precise detail. The general objectives of our studies are to define the mechanism of steroid hormones and their receptors in regulating morphologic differentiation and biochemical specialization in target tissues. This will be accomplished by coordinating a network of investigations designed to uncover the mechanisms by which steroid receptors interact with nuclear regulatory proteins (co-activators, co-repressors, general transcription factors, chromatin modifiers, etc.) to effect target gene expression. We will emphasize experimental dissection of the protein-protein interactions which occur inside a living cell and during transcriptional process; we will define the co-regulator's role in modulating transcription and chromatin structure. In addition, we must understand the mechanisms of positive and negative regulation of receptor functional domains effected by various co-regulators. Our studies will utilize the human progesterone receptor, but to establish regulatory concepts, we will carry out selected experiments using human estrogen, thyroid hormone, and retinoic acid receptors. Cell-free binding and transcription approaches, technologies developed over the past five-year period of this grant, will be a corner stone of our methodology; all new concepts will tested finally in the milieu of the intact cell. These studies will involve aspects of nucleic acid and protein biochemistry, protein purification, cell biology and molecular endocrinology. It is expected that the understanding derived from this project will be relevant to the actions of natural sex steroid hormones relative to human physiology. The following proposed studies should also be pertinent to development of more precise theories for the biochemical mechanism of action of intracellular hormones and receptors in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PAX2 IN MAMMARY DEVELOPMENT AND CANCER Principal Investigator & Institution: Silberstein, Gary B.; Biology; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: PAX2, a paired domain transcription factor, is mitogenic and blocks apoptosis in nephrogenic sem cells during kidney development. We have recently demonstrated PAX2 expression in putative stem cells of normal human mammary epithelium. We have also found PAX2 in >50% of the breast tumor samples investigated (n=38). Functional analyses, using mouse mammary glands in which PAX2 has been ablated, revealed inhibition of progesterone-stimulated growth, as well as reduced expression of critical anti-apoptosis genes, including bcl-2. Our finding of PAX2 expression in the mammary gland is completely novel and has broad implications for understanding the control of differentiation and the abnormal de-differentiation of breast cancer. Based on our preliminary findings, we hypothesize that PAX normally participates in the regulation of the mammary progesterone response and PAX2 overexpression abnormally inhibits apoptosis, possibly contributing to mammary tumorigenesis. We propose to exploit PAX2-null mammary tissue lines, as well as specially developed transgenic mice over-expressing mammary-targeted PAX2, to pursue the following Specific Aims: 1. Characterize growth, morphogenesis and apoptosis in PAX2-null mammary glands. 2. Investigate the mechanisms underlying inhibition of progesterone- stimulated growth in PAX2-null mammary glands. 3. Investigate the influence of PAX2 over-expression on mammary apoptosis. 4. Investigate the effects of PAX2 over-expression on mammary tumorigenesis. The results of these investigations will define the role of PAX2 in the progesterone-signaling pathway in the mammary gland. Over-expression of PAX2 contributes to kidney proliferative disease by persistently blocking apoptosis. It is anticipated that the proposed experiments will contribute to defining a similar role for PAX2 in breast cancer, ultimately suggesting ways to reverse this abnormality and stimulate breast tumor cell death. Finally, the possibility that PAX2 is a mammary tumor promoter will be evaluated, providing insights into mechanisms of breast cancer progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF PROGESTERONE-REGULATED GENES IN EARLY PREGNANCY Principal Investigator & Institution: Bagchi, Indrani C.; Professor; Veterinary Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The steroid hormone progesterone (P) profoundly influences the function of the uterus during establishment and maintenance of pregnancy. The cellular actions of P are mediated through intracellular progesterone receptor (PR) isoforms, PR-A and PR-B, which are well-known transcription factors. It is postulated that hormone-occupied PR triggers the expression of specific gene networks in different cell types within the uterus and the products of these genes mediate the hormonal effects. The long-term goal of this proposal is to identify and functionally characterize the PR-regulated pathways, which are critical mediators of P response within the uterus during early pregnancy. The specific aims of this study are to: 1. Analyze PR isoform-specific regulation and expression of DNA microarray-derived genes in the preimplantation mouse uterus. Oligonucleotide microarrays were utilized to identify several genes whose expression is markedly down regulated in pregnant uterus at the time of implantation in response to a PR antagonist. The PR isoformspecific gene knock-out (KO) mouse models, PRAKO and PRBKO, will be employed to identify the genes that are potentially important for implantation. The spatio-temporal
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expression of these genes in the pregnant uterus will be analyzed. 2. Determine the functional roles of microarray-derived genes in the preimplantation uterus. Using a newly developed methodology, antisense oligodeoxynucleotides directed against mRNA transcripts of selected candidate genes will be administered into the preimplantation uterus to block specific gene expression during implantation. The functional effects of this intervention will be determined. In preliminary studies, antisense ODN-induced blockade of the expression of Irgl in the surface epithelium results in a severe impairment of implantation. The molecular target(s) of Irgl in the pregnant uterus will be identified by yeast two-hybrid approach. 3. Investigate the functional role of the PR-regulated protease inhibitor p12 in the decidual uterus, p12 is a serine protease inhibitor induced by P during trophoblast invasion and decidualization. The target protease(s) of p12 in the pregnant uterus will be identified by in vitro protein interaction methods and proteomics. Additionally, a p12 KO mouse will be developed and analyzed for potential reproductive defects. The proposed study will help us to identify molecules that are critical mediators of P regulation of embryo-uterine interactions during early pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROID HORMONE REGULATION OF ANGIOGENESIS IN ENDOMETRIUM--IMPACT ON FERTILITY Principal Investigator & Institution: Albrecht, Eugene D.; Professor; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: The uterine endometrium undergoes extensive cellular differentiation and development of new blood vessels, i.e. angiogenesis during each menstrual cycle in preparation for implantation. Although estrogen and progesterone have established role in neovascularization, the mechanisms underlying this process have not been established. Specific growth-promoting peptides, i.e. vascular endothelial growth/permeability factor (VEG/PF) and basic fibroblast growth factor (bFGF), stimulate angiogenesis in other systems. Therefore, the present combined basic-clinical research project will utilize in vivo approaches in an established non-human primate model, the baboon, and a microcarrier-based cocultivation system with human endometrial cells to test the hypothesis that estrogen and/or progesterone regulate angiogenesis with the endometrium by stimulating expression of VEG/PR and bFGF and their receptors. In Study 1, angiogenesis, microvascular permeability and expression and cellular localization of VEG/PF and bFGF and their respective tyrosine kinase receptors will be determined in baboons during the normal menstrual cycle and after ovariectomy and the acute or chronic administration of estradiol and/or progesterone. Study 2 will employ an adenovirus-mediated antisense oligonucleotide transfer approach to disrupt the expression of VEG/PF and bFGF in the uterus to test in vivo the hypothesis that these peptides have essential roles upon angiogenesis within the endometrium and consequently upon fertility of the baboon. Study 3 will use a microcarrier cocultivation system to test the hypothesis that estrogen and/or progesterone regulate angiogenesis in human endometrial cells by simulating expression of VEG/PF and bFGF and their receptors. The objective of this study is to transfer the knowledge gained on the physiology and regulation of the angiogenesis system in vivo in the baboon to the study of human endometrial cells in vitro. Completion of this project will provide a fundamental basis for improving our understanding of the etiology of, and establishing in future project years more effective hormonal treatment modalities for, infertility in women.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNERGY BETWEEN SSRIS AND OVARIAN HORMONES Principal Investigator & Institution: Van De Kar, Louis D.; Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 05-AUG-1999; Project End 31-JUL-2004 Summary: Women suffer from disorders associated with serotonin (5-HT) deficiency, such as premenstrual syndrome (PMS) post-partum and post-menopausal depression, anxiety and bulimia. These mood and impulse control disorders are also associated with fluctuations in ovarian hormone levels. Estrogen can be used to treat some of these disorders, but serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac ) are the most effective drugs currently available. A major problem with SSRIs is the delay (2-3 weeks) in onset of clinical improvement of depression, a time which is associated with increased danger of suicide. Treatment with either fluoxetine or estrogen decreases the sensitivity of hypothalamic 5-HT1A receptor systems. These observations suggest that desensitization of 5-HT1A receptor signalling may underlie the therapeutic effectiveness of estrogen and SSRI treatments. Ovarian hormones act predominantly via genomic mechanisms, while fluoxetine induces adaptive responses via membrane proteins. Therefore, our central hypothesis is that estrogen will act synergistically with fluoxetine via complementary mechanisms to desensitize hypothalamic 5-HT1A receptor systems. Based on this hypothesis, we predict that estrogen or estrogen + progesterone will shorten the delay in the effects of SSRIs. The proposed studies will examine the mechanisms by which estrogen: 1) inhibits 5-HT1A signal transduction systems, and 2) reduces the delay in fluoxetine-induced desensitization of hypothalamic 5-HT1A receptor signalling. The proposed studies will use neuroendocrine, biochemical and molecular approaches to study the following specific aims: Specific Aim 1 will determine the doses of estrogen and progesterone that reduce hypothalamic 5-HT1A receptor function in ovariectomized rats. Specific Aim 2 will identify the estrogen receptor subtype(s) which mediate the effect of estrogen on 5-HT1A receptor systems in the hypothalamus. Specific Aim 3 will determine if estrogen shortens the delay in fluoxetine's effects on 5-HT1A receptor signalling. Specific Aim 4 will determine if progesterone increases estrogen's effectiveness in shortening the delay in fluoxetineinduced 5-HT1A receptor sub-sensitivity. The proposed studies will provide the scientific basis for the development of improved therapeutic regimens and novel drugs that provide faster clinical improvement in women suffering from PMS, depression, bulimia and anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHETIC CONTROLS FOR IMMUNOHISTOCHEMICAL ASSAYS Principal Investigator & Institution: Bogen, Steven A.; Associate Professor; Cytologix Corporation 99 Erie St Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2002 Summary: The objective of this proposal is the development of surrogate tissue controls for clinical immunohistochemical (IHC) assays. Presently, each clinical histology laboratory identifies, sections, validates, and archives their own tissue controls. This method is labor-intensive, non-standard, and does not detect either early reagent failure or procedure error. In the Phase I study, we developed synthetic controls for two of the most important analytes in the IHC laboratory - - estrogen and progesterone receptors
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(ER/PR). Our "synthetic" controls are (1) inexpensive, (2) antigen-specific, (3) available in an inexhaustible supply, (4) standardized, (5) stable, for ease of storage, and (6) quantifiable, for providing a reference standard against which to measure assay sensitivity. The Phase II specific aims include: (1) Clinical Validation, leading to FDA clearance for the ER/PR controls, and (2) Development of a complete panel of analyte controls. The first specific aim defines the product's clinical utility. The second aim is an extension of our Phase I technology. We will finish the task started in Phase I, to create a panel of synthetic controls that meet the clinical laboratories' quality control needs. These synthetic controls are a unique tool to verify proper assay performance and minimize analytic error. PROPOSED COMMERCIAL APPLICATIONS: The technology described in this grant proposal will provide the first commercially produced, standardized quality control system for clinical immunohistochemical assays. Controls are important to ensure that a patient's test result is accurate, regardless of which laboratory performs the test. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TGFB REGULATION OF ER RECEPTOR POSITIVE MAMMARY CELLS Principal Investigator & Institution: Barcellos-Hoff, Mary-Helen H.; Staff Scientist; Cell and Molecular Biology; University of Calif-Lawrenc Berkeley Lab Lawrence Berkeley National Laboratory Berkeley, Ca 94720 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Transforming growth factor beta1 (TGF-beta) is widely acknowledged as a potent inhibitor of human and mouse mammary epithelial proliferation. We have localized its activity in the mouse mammary gland and characterized the proliferative phenotype of the Tgfbeta1 heterozygote mouse: both are regulated by the ovarian hormones estrogen and progesterone. It is well known that estrogen signaling through estrogen receptor ? (ER) plays a central role in mammary epithelial cell proliferation. Several recent studies have shown that the majority of estrogen receptor-positive (ER+) cells do not proliferate, but are required to regulate proliferation in ER-negative (ER-) cells via paracrine mechanisms. The small subpopulation (approximately 1% in human and mouse breast) of ER+ cells that maintain proliferative potential has been postulated to be early progenitor cells that could be the origin of ER+ breast cancer. We found that nearly all of the ER+ cells in mouse mammary gland at estrus co-localize with intense TGF-beta activity, consistent with their non-proliferative status. However, proliferation of ER+ cells is increased more than 2-fold in Tgfbeta1 heterozygote mammary gland, which furthermore resulted in a 30% increase in the total number of ER+ cells compared to wildtype mammary epithelium. Based on these observations we hypothesize that TGF-beta actively restrains proliferation of mammary epithelial cells and, in particular, regulates the subpopulation of ER+ cells that are speculated to represent lineage-restricted progenitor. To the extent that stem cells/progenitors are targets for carcinogenesis, we further hypothesize that disruption of TGF-beta action is involved in the genesis of ER+ breast cancer. Our overall goal, therefore, is to define the functional relationship between TGF-beta1 and the population of ER+ replicative cells as a function of age. Three aims are proposed: 1: To determine the frequency of ER+ cells as a function of TGF-beta1 level, localization and activity. 2: To analyze TGF-beta effects on the replicative potential of presumptive mammary stem cells. 3: To determine whether TGF-beta regulation of the ER+ subpopulation contributes to progression and/or features of preneoplastic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE INVOLVEMENT OF THE VMH IN MATERNAL BEHAVIOR IN RATS Principal Investigator & Institution: Mann, Phyllis E.; Veterinary Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant): Based on new evidence from our laboratory, which has discovered an important inhibitory role of the ventromedial nucleus of the hypothalamus (VMH) in maternal behavior, the objective of this grant proposal is to elucidate the involvement of the VMH in the onset of maternal behavior. The experiments described in the present grant proposal will use behavioral, molecular, and anatomical approaches to identify the possible mechanisms of action of the VMH on the inhibition of maternal behavior. The hypothesis underlying the present proposal is that under normal physiological conditions the VMH inhibits the display of maternal behavior in virgin and late-pregnant rats by inhibiting the actions of the medial preoptic area (MPOA, an area considered to be crucially involved in the display of maternal behavior). The specific aim of the first three experiments will be to examine the role of the VMH in the regulation of maternal behavior in estradiol-primed, virgin rats. Experiment 1 will analyze the timing of neurotoxin administration into the VMH and subsequent maternal behavior stimulation. Experiment 2 will determine if infusions of the sodium channel blocker, tetrodotoxin, will stimulate short-latency maternal behavior, while experiment 3 will examine the role of GABA infusions into the VMH and subsequent maternal behavior. The second specific aim is to determine the changes in receptor gene expression of the key pregnancy hormones, estrogen, progesterone, and prolactin, in estradiol-primed, virgin rats. Experiments 4,5 and 6 will use in situ hybridization histochemistiy (ISHH) to determine the changes in estrogen, progesterone, and prolactin receptor gene expression, respectively, in the VMH and MPOA following estradiol stimulation in virgin rats. These 3 experiments will also investigate the changes in receptor gene expression in the MPOA following neurotoxic lesions to the VMH. The third specific aim is to determine, using anatomical, tracktracing methods, whether neurons in the VMH that are activated in the presence of pups project to the MPOA (experiment 7). Experiment 8 will determine the neurotransmitter involved in the regulation of the MPOA by the VMH. Together, these studies will help elucidate the role of the VMH in maternal behavior in virgin rats and identify the neural basis of parental care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF MAP KINASE IN THE CELL CYCLE Principal Investigator & Institution: Ferrell, James E.; Associate Professor; Molecular Pharmacology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-1992; Project End 31-JUL-2006 Summary: (provided by applicant): We have been studying the interplay between cyclin B-Cdc2 and p42 MAPK (ERX2) in Xenopus oocytes, eggs, and cycling egg extracts. Work from our laboratory and others has shown that p42 MAPK is an important upstream activator of Cdc2 during progesterone-induced oocyte maturation. However, as yet we do not know the identity of the progesterone receptor that triggers p42 MAPK activation and oocyte maturation. p42 MAPK can also act as an inhibitor of Cdc2 activation, a role that appears to be physiologically important during the first embryonic cell cycle. The negative regulation of Cdc2 by p42 MAPK has been hypothesized to be a direct effect of p42 MAPK on Wee1, a negative regulator of Cdc2 that is present in
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embryos but absent from oocytes. However, the nature of this regulation is poorly understood. Cdc2 can also activate p42 MAPK, and this appears to be important for maintaining the normal timing of mitotic exit in cycling Xenopus egg extracts, and probably in somatic cells as well. The activation of p42 MAPK by Cdc2 depends upon the MEK1 protein, but does not require either of the known upstream activators of MEK1 identified in Xenopus oocytes and eggs (Mos and Raf-1). Here we propose four specific aims:1. To identify the MAPKKK.through which Cdc2 activates p42 MAPK.2. To determine how p42 MAPK negatively regulates Cdc2 during the first mitotic cell cycle.3. To identify the elusive progesterone receptor that initiates oocyte maturation.4. To examine the systems-level properties of a p42 MAPK cascade reconstituted with recombinant Xenopus proteins.Our overarching aim is to better understand the cell biology and biochemistry of oocyte maturation and early embryogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT Principal Investigator & Institution: Freemark, Michael S.; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-MAY-1988; Project End 31-MAY-2008 Summary: (provided by applicant): Prolactin (PRL) and placental lactogen (PL) stimulate fat deposition, weight gain, and leptin production in rodents and humans, suggesting that lactogens play roles in maternofetal lipid metabolism and obesity. The mechanisms by which lactogens promote fat storage and weight gain are unknown. We hypothesize: (a) that lactogens promote fat deposition through induction of adipogenesis, the process of differentiation of adipocytes from stromal precursors; (b) that adipogenic effects of lactogens are mediated through induction of transcription factors including PPARkhi-2; (c) that PPARkhi-2 induction is mediated through activation of Stat5; and (d) that adipogenic effects of lactogens are modulated by insulin, IGF-1, glucocorticoids, and sex steroids. To test these hypotheses we will examine effects of exogenous PRL and PL on adipogenesis in 3T3-L1 preadipocytes, primary mouse preadipocytes and embryonic fibroblasts and the effects of constitutive expression of PL in a novel 3T3-L1 cell line. To determine if lactogenic signaling is required for preadipocyte differentiation, we will compare rates of adipogenesis in preadipocytes of PRL receptor (PRLR)-deficient mice with rates of adipogenesis in cells of wild-type littermates. To characterize effects of lactogens on PPARkhi expression we will examine effects of PRL and PL on PPARkhi1 and 2 mRNA and protein levels in 3T3-L1 cells, primary preadipoyctes, mouse embryonic fibroblasts and will compare PPARkhi expression in tissues of PRLR deficient mice with that in wild-type littermates, We will examine effects of lactogens on transcriptional activation of the human and mouse PPARkhi-2 promoters expressed in 3T3-L1 cells and will compare the time course of expression of PPARkhi1I and 2 mRNAs in PRL-treated cells with that of ADD1 and c/EBPs beta, delta, and alpha. To test the hypothesis that induction of PPARkhi-2 is mediated through activation of Stat5, we will determine if lactogens induce binding of STAT 5 to consensus binding sites in the human and mPPAR c-2 promoters. We will examine the effect of mutating PPARkhi-2 Stat5 consensus sequences on lactogendependent activation of PPAR gamma2 transcription, and the effect of a dominantnegative STAT5 construct on the induction of PPARkhi mRNA and protein levels in 3T3-L1 cells. Finally, to test the hypothesis that the adipogenic effects of the lactogens are modulated by sex steroids, we will examine the effects of progesterone and estradiol on the adipogenic effects of PRL in 3T3-L 1 cells and the effects of progesterone supplementation on fat deposition and leptin production in PRLR-deficient mice. The
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results of our studies should provide new insist into the roles of pituitary and placental hormones in adipose development and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE INTERACTIONS AND HORMONAL RESPONSES IN THE UTERUS Principal Investigator & Institution: Bigsby, Robert M.; Associate Professor; Obstetrics and Gynecology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 15-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from the applicant's abstract) Knowing how tissue interactions affect physiology is important for understanding pathologies of hormonally regulated organs. In the uterus, tissue interactions mediate steroid hormone effects, playing key roles in events of early pregnancy. Although estrogen regulates cell signaling in a stroma-to-epithelium direction in the uterus, a paracrine factor mediating this effect has not been identified. Also, hormonal regulation of a pathway in the reciprocal direction has not been studied. In both human and rodent, estrogen stimulation of a progesterone dominated uterus causes proliferation of the endometrial stroma. Proposed studies will test the hypothesis: 1) Progesterone priming for and estrogen induction of cellular proliferation in the uterine stroma occurs indirectly through activation of progesterone receptor (PR) and estrogen receptor-alpha (ER alpha) in the overlying epithelium. 2) IGF-I is a paracrine mediator of steroid action in the uterus. The hypothesis will be tested using tissue recombinations grown in xenograft. Uterine epithelium (epi) and mesenchyme (mes) will be derived from neonatal wild-type mice, ER alpha knockout (ER alpha KO) mice, PR knockout (PRKO) mice, or IGF-I knockout mice. These knockout models were chosen because: ER alpha KO mouse uterus shows no growth response to estradiol stimulation, indicating that it is devoid of any growth-promoting ER; PRKO mouse uterus exhibits no stromal response to progesterone/estrogen treatment or to a decidualizing stimulus; in the IGF-I knockout mouse uterus estrogen stimulated cells are arrested in G2. The specific aims are: 1. Determine the tissue specificity of the steroid receptor-mediated events regulating cell proliferation. 2. Determine the role of tissue specific expression of IGF-I in mediation of steroid induced proliferation in the uterus. For each type of knockout animal, tissue will be separated and recombined in all 4 possible combinations: epi+/mes+, epi-/mes-, epi+/mes-, epi/mes+ (+, target gene status). Tissue recombinants will be grown in athymic mice. Effects of hormone treatments will be tested using tritiated thymidine incorporation or mitotic index as the endpoint. If hypothesis 1 proves correct, this will be a novel demonstration of hormonal regulation via an epithelium-to-stroma interaction, thereby leading to a new concept of hormone action in steroid-responsive organs. If IGF-I proves critical for tissue interactions it will be the first paracrine factor to be definitively identified as a mediator of steroid action in the uterus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TROPHOBLAST MDR EFFLUX SYSTEM AND FETAL PROTECTION Principal Investigator & Institution: Audus, Kenneth L.; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: Recent studies in animal models have indicated that the multi-drug resistant (MDR) gene product, P-glycoprotein (Pgp), of the placenta has a significant role in
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reducing chemical exposure to the fetus and the incidence of birth defects. Pgp is an active, polyspecific membrane- bound transporter expressed in tumor and normal tissues, including the placenta. In humans, Pgp is localized to the syncytio- and cytotrophoblasts and is expressed throughout pregnancy. However, Pgp's role in controlling the disposition of drugs and steroids between the fetal and maternal compartments is unknown. The objective of this proposal is to characterize the Pgp efflux mechanism of the trophoblast with respect to expression and transporting xenobiotics (e.g., anti-cancer agents, phenobarbital, rifampicin) and steroids of pregnancy (e.g., progesterone) and its regulation by these substances. Under Aim 1o of this proposal we will elucidate (a) the mRNA and protein expression, and (b) the localization of MDR1 in the human trophoblast. In Aim 2 we will determine (a) the functional significance and (b) the asymmetry of human trophoblast transport of selected xenobiotics and steroid hormones. Aim 3 studies are directed at characterization of the regulatory mechanism(s) by which certain xenobiotics and steroid hormones control (a) the expression and (b) the function of MDR1 of the human trophoblast. We expect that at the conclusion of this proposal we will have established the role of Pgp and related mechanisms (e.g. breast cancer resistance protein) of the trophoblast in transporting substrates that include xenobiotics and the steroid hormones. We also expect to establish a putative role and the biochemical mechanisms by which certain xenobiotics and steroid hormones modulate Pgp expression and/or function. Our long term goal is to develop a detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human trophoblast and to identify appropriate in vitro techniques that can lead the way to the future design and development of drugs for pregnancy that reduce risk to the health of the fetus and the mother. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TUMOR MARKERS TO PREDICT TREATMENT RESPONSE Principal Investigator & Institution: Dressler, Lynn G.; Comprehensive Cancer Center; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 10-SEP-2001; Project End 31-AUG-2006 Summary: (Applicant?s Description): This revised application for funding is part of a multidisciplinary CALGB research project targeting elderly women with breast cancer. This study is a laboratory companion to the clinical trial proposed by the CALGB, entitled," A Randomized Trial of Adjuvant Chemotherapy with Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil- "CMF" or Cyclophosphamide and Doxorubicin -"AC" versus Capecitabine in Women 65 Years and Older with Early?? Stage Breast cancer. The primary aim of the clinical trial is to compare the effectiveness of standard chemotherapy regimens (CMF or AC) with a less toxic, single agent (Capecitabine), with respect to five-year relapse free survival in women 65 years and older with early stage breast cancer. The laboratory companion is designed to evaluate tumor specimens (formalin-fixed paraffin-embedded, FFPE) that are collected as part of the CALGB clinical trial to examine the relationships between biological markers of tumor progression and clinical outcome in elderly women with early stage breast cancer. We have selected tumor markers that are associated with metabolic pathways of chemotherapy action as well as those associated with common pathways of tumor progression. We will evaluate whether specific markers of capecitabine metabolism, thymidylate synthetase, thymidine phosphorylase and dihyodropyrimidine dehydrogenase gene expression (mRNA) can predict recurrence and survival in patients
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treated with capecitabine. We will also determine whether local regional or distant failure can be predicted in this population based on a tumor marker profile that reflects markers of genetic instability/proliferation in the primary tumors, (protein expression of p53, erbB2/HER2, and KI-67 (MIB-1) as well as markers of invasion and metastasis (angeogenesis, focal adhesion kinase, VEGF and e-cadherin). The expression of these markers will be correlated with conventional markers of tumor size, histologic and nuclear grade, and estrogen and progesterone receptor status. In addition, comparisons of tumor marker expression between elderly and younger populations with node positive breast cancer (patients from this adjuvant chemotherapy trial and CALGB 8541) will be performed. It will also be possible to compare tumor marker expression between elderly patients with stage I and stage II breast cancer (patients from this adjuvant chemotherapy trial and CALGB 9343). Two subcontracts are included in this proposal, one to support the CALGB Pathology Coordinating Office functions at OSU relevant to this study and the other in support of the molecular studies being performed by USC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VAGINAL DRUG DELIVERY OF P-GLYCOPROTEIN SUBSTRATES Principal Investigator & Institution: Pauletti, Giovanni M.; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The long-term goal of our research is to improve systemic delivery of drugs with limited oral bioavailability due to extensive first-pass elimination by means of site-specific vaginal administration in the female. The central hypothesis of the present proposal is that progesterone regulates functional expression of P-glycoprotein (P-gp) in the vaginal mucosa leading to variable drug efflux. As a consequence, maximum vaginal bioavailability of P-gp substrates is restricted to a defined time window during the menstrual cycle. The MDR1 gene product P-gp is a prototype of membrane efflux systems that limit transcellular transport of drug molecules with broad specificity at strategic epithelial and endothelial membrane barriers, including the gastrointestinal mucosa. Thus, there are three specific aims proposed: (l) To test the hypothesis that progesterone regulates P-gp expression in human vaginal mucosa in vivo and in vitro. (2) To determine whether P-gp efflux activity in human vaginal epithelial cells in vitro is regulated by progesterone. (3) To test the prediction that progesterone regulates P-gp expression at the transcriptional level. Northern blot analysis will be conducted to quantify mRNA of P-gp in biopsies of human vaginal mucosa collected during the menstrual cycle as well as progesteronetreated immortalized human vaginal epithelial cells. Protein expression in response to cyclic hormonal changes will be determined by immunoblot analysis. Functional activity of P-gp will be assessed in vitro using intracellular accumulation of the P-gp substrate digoxin. Experiments will be designed to determine whether progesterone-induced changes in digoxin accumulation satisfy established criteria for P-gp-mediated efflux, including directionality, dependency on energy and substrate concentration, and sensitivity to selective inhibition. Finally, promoter/reporter constructs will be prepared to determine DNA sequences in the upstream region of the MDR1 gene that facilitate progesterone signaling. The significance of this research is that it will set the stage for future mechanistic studies to elucidate the interplay of female reproductive hormones in the regulation of vaginal P-gp. From the drug delivery point of view, the results may be applicable to determine an optimum time window during the menstrual cycle for effective vaginal delivery of P-gp substrates in order to maximize systemic bioavailability.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “progesterone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for progesterone in the PubMed Central database: •
16[alpha]-Substituted Analogs of the Antiprogestin RU486 Induce a Unique Conformation in the Human Progesterone Receptor Resulting in Mixed Agonist Activity. by Wagner BL, Pollio G, Leonhardt S, Wani MC, Lee DY, Imhof MO, Edwards DP, Cook CE, McDonnell DP.; 1996 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38743
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4-Aminopyridine Decreases Progesterone Production by Porcine Granulosa Cells. by Li Y, Ganta S, von Stein FB, Mason DE, Mitchell BM, Freeman LC.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155641
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8-Bromo-Cyclic AMP Induces Phosphorylation of Two Sites in SRC-1 That Facilitate Ligand-Independent Activation of the Chicken Progesterone Receptor and Are Critical for Functional Cooperation between SRC-1 and CREB Binding Protein. by Rowan BG, Garrison N, Weigel NL, O'Malley BW.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86491
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A dynamic shift of VEGF isoforms with a transient and selective progesteroneinduced expression of VEGF189 regulates angiogenesis and vascular permeability in human uterus. by Ancelin M, Buteau-Lozano H, Meduri G, Osborne-Pellegrin M, Sordello S, Plouet J, Perrot-Applanat M.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122895
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A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk. by De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, Hunter DJ.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129433
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A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors. by Krebs CJ, Jarvis ED, Chan J, Lydon JP, Ogawa S, Pfaff DW.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18847
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A paracrine role for the epithelial progesterone receptor in mammary gland development. by Brisken C, Park S, Vass T, Lydon JP, O'Malley BW, Weinberg RA.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20216
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A Progesterone Metabolite Stimulates the Release of Gonadotropin-Releasing Hormone from GT1-1 Hypothalamic Neurons via the [gamma]-Aminobutyric Acid Type A Receptor. by El-Etr M, Akwa Y, Fiddes RJ, Robel P, Baulieu E.; 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42043
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A Specific Membrane Binding Protein for Progesterone in Rat Brain: Sex Differences and Induction by Estrogen. by Tischkau SA, Ramirez VD.; 1993 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45857
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Activation of the kinin system in the ovary during ovulation: Role of endogenous progesterone. by Brann DW, Greenbaum LM, Mahesh VB, Gao X.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111191
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Activity and expression of progesterone metabolizing 5[alpha]-reductase, 20[alpha]hydroxysteroid oxidoreductase and 3[alpha]([beta])-hydroxysteroid oxidoreductases in tumorigenic (MCF-7, MDA-MB-231, T-47D) and nontumorigenic (MCF-10A) human breast cancer cells. by Wiebe JP, Lewis MJ.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154104
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Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. by Webster JI, Tonelli LH, Moayeri M, Simons SS Jr, Leppla SH, Sternberg EM.; 2003 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156265
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Antiprogestins Prevent Progesterone Receptor Binding to Hormone Responsive Elements in vivo. by Truss M, Bartsch J, Beato M.; 1994 Nov 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45225
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Brain 5[alpha]-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. by Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30228
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Chlamydia trachomatis Infection in the Female Reproductive Tract of the Rat: Influence of Progesterone on Infectivity and Immune Response. by Kaushic C, Murdin AD, Underdown BJ, Wira CR.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107992
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Counting the costs: Comparing depot medroxyprogesterone acetate and norethisterone oenanthate utilisation patterns in South Africa. by Smit J, Gray A, McFadyen L, Zuma K.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32302
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Crosslinking of progesterone receptor to DNA using tuneable nanosecond, picosecond and femtosecond UV laser pulses. by Russmann C, Truss M, Fix A, Naumer C, Herrmann T, Schmitt J, Stollhof J, Beigang R, Beato M.; 1997 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146765
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Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. by Tanenbaum DM, Wang Y, Williams SP, Sigler PB.; 1998 May 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27574
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Dimerization of Mammalian Progesterone Receptors Occurs in the Absence of DNA and is Related to the Release of the 90-kDa Heat Shock Protein. by DeMarzo AM, Beck CA, Onate SA, Edwards DP.; 1991 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50750
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Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor [alpha] knockout mouse uterus. by Curtis SW, Clark J, Myers P, Korach KS.; 1999 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22348
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E1A-Mediated Repression of Progesterone Receptor-Dependent Transactivation Involves Inhibition of the Assembly of a Multisubunit Coactivation Complex. by Xu Y, Klein-Hitpass L, Bagchi MK.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110830
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Effect of long-term treatment with steroid hormones or tamoxifen on the progesterone receptor and androgen receptor in the endometrium of ovariectomized cynomolgus macaques. by Wang H, Isaksson E, von Schoultz B, Cline JM, Sahlin L.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151802
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Effects of Estradiol and Progesterone on Susceptibility and Early Immune Responses to Chlamydia trachomatis Infection in the Female Reproductive Tract. by Kaushic C, Zhou F, Murdin AD, Wira CR.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101727
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Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review. by Wyatt K, Dimmock P, Jones P, Obhrai M, O'Brien S.; 2001 Oct 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57352
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Estrogen Receptor and Progesterone Receptor Genes are Expressed Differentially in Mouse Embryos During Preimplantation Development. by Hou Q, Gorski J.; 1993 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47588
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Estrogen, Progesterone and Epithelial Ovarian Cancer. by Ho SM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=239900
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Estrogen-induced transcription of the progesterone receptor gene does not parallel estrogen receptor occupancy. by Lee Y, Gorski J.; 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26377
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Expression of Endogenous Betaretroviruses in the Ovine Uterus: Effects of Neonatal Age, Estrous Cycle, Pregnancy, and Progesterone. by Palmarini M, Gray CA, Carpenter K, Fan H, Bazer FW, Spencer TE.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114717
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Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue. by Smith RA, Lea RA, Curran JE, Weinstein SR, Griffiths LR.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154135
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Expression of human estrogen receptor-[alpha] and -[beta], progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. by Lau KM, Mok SC, Ho SM.; 1999 May 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21927
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Gender-related plasma levels of progesterone, interleukin-8 and interleukin-10 during and after cardiopulmonary bypass in infants and children. by Trotter A, Muck K, Grill HJ, Schirmer U, Hannekum A, Lang D.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=83856
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Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2 /EP2 receptor pathway. by Elvin JA, Yan C, Matzuk MM.; 2000 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27877
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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. by Labriola L, Salatino M, Proietti CJ, Pecci A, Coso OA, Kornblihtt AR, Charreau EH, Elizalde PV.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140689
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Heterotetrameric Structure of the Human Progesterone Receptor. by Rehberger P, Rexin M, Gehring U.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49843
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Hormone-Induced Progesterone Receptor Phosphorylation Consists of Sequential DNA-Independent and DNA-Dependent Stages: Analysis with Zinc Finger Mutants and the Progesterone Antagonist ZK98299. by Takimoto GS, Tasset DM, Eppert AC, Horwitz KB.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48801
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Identification of XPR-1, a progesterone receptor required for Xenopus oocyte activation. by Tian J, Kim S, Heilig E, Ruderman JV.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18923
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Impact of progesterone receptor on cell-fate decisions during mammary gland development. by Shyamala G, Yang X, Cardiff RD, Dale E.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16189
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Jun Dimerization Protein 2 Functions as a Progesterone Receptor N-Terminal Domain Coactivator. by Wardell SE, Boonyaratanakornkit V, Adelman JS, Aronheim A, Edwards DP.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133955
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Ligand and DNA-Dependent Phosphorylation of Human Progesterone Receptor in vitro. by Bagchi MK, Tsai SY, Tsai M, O'Malley BW.; 1992 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48722
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Ligand-Dependent Conformational Changes in the Progesterone Receptor are Necessary for Events that Follow DNA Binding. by Allan GF, Tsai SY, Tsai M, O'Malley BW.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50634
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Membrane-bound progesterone receptors contain a cytochrome b5-like ligandbinding domain. by Mifsud W, Bateman A.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151170
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Midcycle Administration of a Progesterone Synthesis Inhibitor Prevents Ovulation in Primates. by Hibbert ML, Stouffer RL, Wolf DP, Zelinski-Wooten MB.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39879
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Modulation of AP-1 Activity by the Human Progesterone Receptor in Endometrial Adenocarcinoma Cells. by Bamberger A, Bamberger CM, Gellersen B, Schulte HM.; 1996 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39208
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Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor. by Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, Butts RN, Smith DF.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231784
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Mutation of Hip's Carboxy-Terminal Region Inhibits a Transitional Stage of Progesterone Receptor Assembly. by Prapapanich V, Chen S, Smith DF.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108806
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Newly Expressed Progesterone Receptor Cannot Activate Stable, Replicated Mouse Mammary Tumor Virus Templates but Acquires Transactivation Potential Upon Continuous Expression. by Smith CL, Archer TK, Hamlin-Green G, Hager GL.; 1993 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47950
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Nuclear Progesterone Receptor is Mainly Heat Shock Protein 90-Free in vivo. by Tuohimaa P, Pekki A, Blauer M, Joensuu T, Vilja P, Ylikomi T.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46820
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Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. by Lange CA, Shen T, Horwitz KB.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15511
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Progesterone and Glucocorticoid Receptors Recruit Distinct Coactivator Complexes and Promote Distinct Patterns of Local Chromatin Modification. by Li X, Wong J, Tsai SY, Tsai MJ, O'Malley BW.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155204
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Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. by Chan WK, Klock G, Bernard HU.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250897
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Progesterone and RU486: Opposing Effects on Human Sperm. by Yang J, Serres C, Philibert D, Robel P, Baulieu E, Jouannet P.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42982
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Progesterone Increases Susceptibility and Decreases Immune Responses to Genital Herpes Infection. by Kaushic C, Ashkar AA, Reid LA, Rosenthal KL.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152159
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Progesterone Inhibits Estrogen-Induced Cyclin D1 and cdk4 Nuclear Translocation, Cyclin E- and Cyclin A-cdk2 Kinase Activation, and Cell Proliferation in Uterine Epithelial Cells in Mice. by Tong W, Pollard JW.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84018
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Progesterone Modulates a Neuronal Nicotinic Acetylcholine Receptor. by Valera S, Ballivet M, Bertrand D.; 1992 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50251
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Progesterone receptor and dopamine receptors are required in [Delta]9tetrahydrocannabinol modulation of sexual receptivity in female rats. by Mani SK, Mitchell A, O'Malley BW.; 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14740
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Progesterone receptor knockout mice have an improved glucose homeostasis secondary to [beta]-cell proliferation. by Picard F, Wanatabe M, Schoonjans K, Lydon J, O'Malley BW, Auwerx J.; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137770
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Progesterone receptor structure and function altered by geldanamycin, an hsp90binding agent. by Smith DF, Whitesell L, Nair SC, Chen S, Prapapanich V, Rimerman RA.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230934
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Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility. by Tibbetts TA, DeMayo F, Rich S, Conneely OM, O'Malley BW.; 1999 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18405
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Progesterone receptors mediate male aggression toward infants. by Schneider JS, Stone MK, Wynne-Edwards KE, Horton TH, Lydon J, O'Malley B, Levine JE.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151447
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Progesterone Regulates the Activity of Collagenase and Related Gelatinases A and B in Human Endometrial Explants. by Marbaix E, Donnez J, Courtoy PJ, Eeckhout Y.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50642
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Progesterone Synthesized by Schwann Cells during Myelin Formation Regulates Neuronal Gene Expression. by Chan JR, Rodriguez-Waitkus PM, Ng BK, Liang P, Glaser M.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14919
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Progesterone-metabolite prevents protein kinase C-dependent modulation of [gamma]-aminobutyric acid type A receptors in oxytocin neurons. by Brussaard AB, Wossink J, Lodder JC, Kits KS.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16290
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Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. by Robker RL, Russell DL, Espey LL, Lydon JP, O'Malley BW, Richards JS.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18294
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Protective Effect of Medroxyprogesterone Acetate Plus Testosterone Against Radiation-Induced Damage to the Reproductive Function of Male Rats and Their Offspring. by Jegou B, Velez de la Calle JF, Bauche F.; 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52579
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Saccharomyces cerevisiae Dap1p, a Novel DNA Damage Response Protein Related to the Mammalian Membrane-Associated Progesterone Receptor. by Hand RA, Jia N, Bard M, Craven RJ.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154842
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Sequential recruitment of steroid receptor coactivator-1 (SRC-1) and p300 enhances progesterone receptor-dependent initiation and reinitiation of transcription from chromatin. by Liu Z, Wong J, Tsai SY, Tsai MJ, O'Malley BW.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60070
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Stimulation of 16-dehydroprogesterone and progesterone reductases of Eubacterium sp. strain 144 by hemin and hydrogen or pyruvate. by Glass TL, Burley CZ.; 1985 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238521
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The Antibiotic Azatyrosine Suppresses Progesterone or [Val12]p21 Ha-ras/Insulinlike Growth Factor I-Induced Germinal Vesicle Breakdown and Tyrosine Phosphorylation of Xenopus Mitogen-Activated Protein Kinase in Oocytes. by Campa MJ, Glickman JF, Yamamoto K, Chang K.; 1992 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49769
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The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism. by Bayaa M, Booth RA, Sheng Y, Liu XJ.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18811
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The elusive progesterone receptor in Xenopus oocytes. by Maller JL.; 2001 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33348
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The Extreme C Terminus of Progesterone Receptor Contains a Transcriptional Repressor Domain that Functions through a Putative Corepressor. by Xu J, Nawaz Z, Tsai SY, Tsai M, O'Malley BW.; 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=37966
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The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor. by Skinner DC, Evans NP, Delaleu B, Goodman RL, Bouchard P, Caraty A.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28006
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The Nuclear Corepressors NCoR and SMRT Are Key Regulators of Both Ligand- and 8-Bromo-Cyclic AMP-Dependent Transcriptional Activity of the Human Progesterone Receptor. by Wagner BL, Norris JD, Knotts TA, Weigel NL, McDonnell DP.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108850
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The Opposing Transcriptional Activities of the Two Isoforms of the Human Progesterone Receptor Are Due to Differential Cofactor Binding. by Giangrande PH, A. Kimbrel E, Edwards DP, McDonnell DP.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85605
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The Progesterone Antagonist RU486 Acquires Agonist Activity upon Stimulation of cAMP Signaling Pathways. by Beck CA, Weigel NL, Moyer ML, Nordeen SK, Edwards DP.; 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46527
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The temporal reliability of serum estrogens, progesterone, gonadotropins, SHBG and urinary estrogen and progesterone metabolites in premenopausal women. by Williams AE, Maskarinec G, Franke AA, Stanczyk FZ.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140038
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Transcriptional Hyperactivity of Human Progesterone Receptors Is Coupled to Their Ligand-Dependent Down-Regulation by Mitogen-Activated Protein KinaseDependent Phosphorylation of Serine 294. by Shen T, Horwitz KB, Lange CA.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87329
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Transcriptional regulation of the mouse steroid 5[alpha]-reductase type II gene by progesterone in brain. by Matsui D, Sakari M, Sato T, Murayama A, Takada I, Kim M, Takeyama KI, Kato S.; 2002 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101357
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Transforming Growth Factor [beta] Mediates the Progesterone Suppression of an Epithelial Metalloproteinase by Adjacent Stroma in the Human Endometrium. by Bruner KL, Rodgers WH, Gold LI, Korc M, Hargrove JT, Matrisian LM, Osteen KG.; 1995 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41339
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Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands. by Shyamala G, Yang X, Silberstein G, Barcellos-Hoff MH, Dale E.; 1998 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18483
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Two Distinct Mechanisms Control the Accumulation of Cyclin B1 and Mos in Xenopus Oocytes in Response to Progesterone. by Frank-Vaillant M, Jessus C, Ozon R, Maller JL, Haccard O.; 1999 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25591
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Two Domains of the Progesterone Receptor Interact with the Estrogen Receptor and Are Required for Progesterone Activation of the c-Src/Erk Pathway in Mammalian Cells. by Ballare C, Uhrig M, Bechtold T, Sancho E, Di Domenico M, Migliaccio A, Auricchio F, Beato M.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149459
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Yeast RSP5 and its human homolog hRPF1 potentiate hormone-dependent activation of transcription by human progesterone and glucocorticoid receptors. by Imhof MO, McDonnell DP.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231250
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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 progesterone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “progesterone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for progesterone (hyperlinks lead to article summaries): •
11beta-hydroxyprogesterone acts as a mineralocorticoid agonist in stimulating Na+ absorption in mammalian principal cortical collecting duct cells. Author(s): Rafestin-Oblin ME, Fagart J, Souque A, Seguin C, Bens M, Vandewalle A. Source: Molecular Pharmacology. 2002 December; 62(6): 1306-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435797&dopt=Abstract
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5'-p-Fluorosulfonylbenzoyl adenosine inhibits progesterone synthesis in human placental mitochondria. Author(s): Flores-Herrera O, Uribe A, Garcia-Perez C, Milan R, Martinez F. Source: Biochimica Et Biophysica Acta. 2002 November 8; 1585(1): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457710&dopt=Abstract
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6alpha-Methyl-16alpha,17alpha-cyclohexane progesterone and progesterone inhibit growth of doxorubicin-sensitive MCF-7 and HeLa tumor cells. Author(s): Shimanovskii NL, Semeikin AV, Fedotcheva TA, Fedosov AV, Kamernitskii AV, Levina IS. Source: Bulletin of Experimental Biology and Medicine. 2002 October; 134(4): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533767&dopt=Abstract
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A 2-year prospective study on the effects of depot medroxyprogesterone acetate on bone mass-response to estrogen and calcium therapy in individual users. Author(s): Merki-Feld GS, Neff M, Keller PJ. Source: Contraception. 2003 February; 67(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586317&dopt=Abstract
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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 decline in the levels of progesterone receptor coactivators in the pregnant uterus at term may antagonize progesterone receptor function and contribute to the initiation of parturition. Author(s): Condon JC, Jeyasuria P, Faust JM, Wilson JW, Mendelson CR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 5; 100(16): 9518-23. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886011&dopt=Abstract
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A functional polymorphism in the progesterone receptor gene is associated with an increase in breast cancer risk. Author(s): De Vivo I, Hankinson SE, Colditz GA, Hunter DJ. Source: Cancer Research. 2003 September 1; 63(17): 5236-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500352&dopt=Abstract
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A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk. Author(s): De Vivo I, Huggins GS, Hankinson SE, Lescault PJ, Boezen M, Colditz GA, Hunter DJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 September 17; 99(19): 12263-8. Epub 2002 Sep 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218173&dopt=Abstract
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A mutated progesterone receptor allele is more prevalent in unexplained infertility. Author(s): Pisarska MD, Carson SA, Casson PR, Tong X, Buster JE, Kieback DG. Source: Fertility and Sterility. 2003 September; 80(3): 651-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969718&dopt=Abstract
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A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate. Author(s): Cundy T, Ames R, Horne A, Clearwater J, Roberts H, Gamble G, Reid IR. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 January; 88(1): 7881. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519833&dopt=Abstract
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A study of extra genital effects of estrogen and progesterone. Author(s): Das AK, Majumdar A, Singh MA. Source: Indian J Physiol Pharmacol. 2002 April; 46(2): 175-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500492&dopt=Abstract
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Accumulation of uPA-PAI-1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer. Author(s): Schneider J, Pollan M, Tejerina A, Sanchez J, Lucas AR. Source: British Journal of Cancer. 2003 January 13; 88(1): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556966&dopt=Abstract
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Adjuvant endocrine treatment with medroxyprogesterone acetate or tamoxifen in stage I and II endometrial cancer--a multicentre, open, controlled, prospectively randomised trial. Author(s): von Minckwitz G, Loibl S, Brunnert K, Kreienberg R, Melchert F, Mosch R, Neises M, Schermann J, Seufert R, Stiglmayer R, Stosiek U, Kaufmann M. Source: European Journal of Cancer (Oxford, England : 1990). 2002 November; 38(17): 2265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441263&dopt=Abstract
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Aldosterone- and progesterone-membrane-binding proteins: new concepts of nongenomic steroid action. Author(s): Haseroth K, Christ M, Falkenstein E, Wehling M. Source: Current Protein & Peptide Science. 2000 December; 1(4): 385-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369906&dopt=Abstract
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An antiprogesterone, onapristone, enhances the gene expression of promatrix metalloproteinase 3/prostromelysin-1 in the uterine cervix of pregnant rabbit. Author(s): Imada K, Sato T, Hashizume K, Tanimoto A, Sasaguri Y, Ito A. Source: Biological & Pharmaceutical Bulletin. 2002 September; 25(9): 1223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230124&dopt=Abstract
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An Sp1-NF-Y/progesterone receptor DNA binding-dependent mechanism regulates progesterone-induced transcriptional activation of the rabbit RUSH/SMARCA3 gene. Author(s): Hewetson A, Chilton BS. Source: The Journal of Biological Chemistry. 2003 October 10; 278(41): 40177-85. Epub 2003 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890680&dopt=Abstract
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Analysis of estrogen receptor (ERalpha and ERbeta) and progesterone receptor (PR) polymorphisms in uterine leiomyomas. Author(s): Massart F, Becherini L, Marini F, Noci I, Piciocchi L, Del Monte F, Masi L, Falchetti A, Tanini A, Scarselli G, Brandi L. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 January; 9(1): Br25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552233&dopt=Abstract
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Analysis of the human progesterone receptor gene polymorphism PROGINS in Austrian ovarian cancer patients. Author(s): Whittemore AS, McGuire V. Source: International Journal of Cancer. Journal International Du Cancer. 2002 September 10; 101(2): 202; Author Reply 203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210000&dopt=Abstract
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Androgen receptor expression in ductal carcinoma in situ of the breast: relation to oestrogen and progesterone receptors. Author(s): Kasami M, Page DL. Source: Journal of Clinical Pathology. 2002 November; 55(11): 879; Author Reply 879. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401835&dopt=Abstract
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Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone. Author(s): Oelkers W. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2002 December; 7 Suppl 3: 1926; Discussion 42-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659403&dopt=Abstract
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Anti-proliferative effects of progesterone antagonists in the primate endometrium: a potential role for the androgen receptor. Author(s): Brenner RM, Slayden OD, Critchley HO. Source: Reproduction (Cambridge, England). 2002 August; 124(2): 167-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141929&dopt=Abstract
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Association of progesterone receptor and HER2 expressions with the survival time of patient with breast cancer. Author(s): Mai GF, Zheng H, Luo RC, Liao WJ, Zhang LS, He XB. Source: Di Yi June Yi Da Xue Xue Bao. 2003 April; 23(4): 372-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697480&dopt=Abstract
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Asymmetric binding of histone H1 stabilizes MMTV nucleosomes and the interaction of progesterone receptor with the exposed HRE. Author(s): Vicent GP, Melia MJ, Beato M. Source: Journal of Molecular Biology. 2002 November 29; 324(3): 501-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445785&dopt=Abstract
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Autoimmune progesterone dermatitis and its manifestation as anaphylaxis: a case report and literature review. Author(s): Snyder JL, Krishnaswamy G. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 May; 90(5): 469-77; Quiz 477, 571. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775127&dopt=Abstract
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Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: Confirmation of progesterone sensitivity by in vitro interferon-gamma release. Author(s): Halevy S, Cohen AD, Lunenfeld E, Grossman N. Source: Journal of the American Academy of Dermatology. 2002 August; 47(2): 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140482&dopt=Abstract
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Autoimmune progesterone dermatitis. Author(s): Oskay T, Kutluay L, Kaptanoglu A, Karabacak O. Source: Eur J Dermatol. 2002 November-December; 12(6): 589-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459536&dopt=Abstract
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Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status. Author(s): Sawh RN, Malpica A, Deavers MT, Liu J, Silva EG. Source: Human Pathology. 2003 April; 34(4): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733118&dopt=Abstract
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Bleeding patterns in women using intramuscular progesterone for luteal support in in-vitro fertilisation cycles. Author(s): Gurbuz B, Yalti S, Ficicioglu C, Delikara N, Alpay Z. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850858&dopt=Abstract
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Bone mineral density at various anatomic bone sites in women receiving combined oral contraceptives and depot-medroxyprogesterone acetate for contraception. Author(s): Wanichsetakul P, Kamudhamas A, Watanaruangkovit P, Siripakarn Y, Visutakul P. Source: Contraception. 2002 June; 65(6): 407-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127638&dopt=Abstract
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Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years. Author(s): Busen NH, Britt RB, Rianon N. Source: The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. 2003 April; 32(4): 257-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667729&dopt=Abstract
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Bone mineral density in adolescent and young Thai girls receiving oral contraceptives compared with depot medroxyprogesterone acetate: a cross-sectional study in young Thai women. Author(s): Tharnprisarn W, Taneepanichskul S. Source: Contraception. 2002 August; 66(2): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204782&dopt=Abstract
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Breast carcinoma in women over the age of 85: distinct histological pattern and androgen, oestrogen, and progesterone receptor status. Author(s): Honma N, Sakamoto G, Akiyama F, Esaki Y, Sawabe M, Arai T, Hosoi T, Harada N, Younes M, Takubo K. Source: Histopathology. 2003 February; 42(2): 120-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558743&dopt=Abstract
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C16 and C17 substituted derivatives of pregnenolone and progesterone as inhibitors of 17alpha-hydroxylase-C17, 20-lyase: synthesis and biological evaluation. Author(s): Haidar S, Hartmann RW. Source: Archiv Der Pharmazie. 2002; 335(11-12): 526-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596217&dopt=Abstract
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Carbon dioxide production during acetazolamide and medroxyprogesterone treatment. Author(s): Cole RP. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 April; 21(4): 733; Author Reply 734. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762366&dopt=Abstract
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Characterisation of oestrogen receptor, progesterone receptor, trefoil factor 1, and epidermal growth factor and its receptor in pancreatic cystic neoplasms and pancreatic ductal adenocarcinoma. Author(s): Yeh TS, Jan YY, Chiu CT, Ho YB, Chen TC, Lee KF, Chan KM, Hsu JC, Hwang TL, Chen MF. Source: Gut. 2002 November; 51(5): 712-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377812&dopt=Abstract
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Circadian rhythm of salivary cortisol, 17alpha-hydroxyprogesterone, and progesterone in healthy children. Author(s): Groschl M, Rauh M, Dorr HG. Source: Clinical Chemistry. 2003 October; 49(10): 1688-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500602&dopt=Abstract
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Clinical validation of a fully automated 17beta-estradiol and progesterone assay (VIDAS) for use in monitoring assisted reproduction treatment. Author(s): Anckaert E, Mees M, Schiettecatte J, Smitz J. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 August; 40(8): 824-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392313&dopt=Abstract
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Combination therapy of low-dose medroxyprogesterone acetate and oral estrogen does not affect endothelial function in the forearms of postmenopausal women. Author(s): Sanada M, Higashi Y, Nakagawa K, Tsuda M, Kodama I, Nagai N, Chayama K, Ohama K. Source: Menopause (New York, N.Y.). 2002 September-October; 9(5): 360-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218725&dopt=Abstract
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Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients. Author(s): Wagenaar M, Vos PJ, Heijdra YF, Teppema LJ, Folgering HT. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 November; 20(5): 1130-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449165&dopt=Abstract
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Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD. Author(s): Wagenaar M, Vos P, Heijdra Y, Teppema L, Folgering H. Source: Chest. 2003 May; 123(5): 1450-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740260&dopt=Abstract
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Comparison of different antibodies for detection of progesterone receptor in breast cancer. Author(s): Press M, Spaulding B, Groshen S, Kaminsky D, Hagerty M, Sherman L, Christensen K, Edwards DP. Source: Steroids. 2002 August; 67(9): 799-813. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123792&dopt=Abstract
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Comparison of the effects of 17beta-E2 and progesterone on the expression of osteoprotegerin in normal human osteoblast-like cells. Author(s): Liao EY, Luo XH, Su X. Source: J Endocrinol Invest. 2002 October; 25(9): 785-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398237&dopt=Abstract
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Complex role of histone H1 in transactivation of MMTV promoter chromatin by progesterone receptor. Author(s): Vicent GP, Koop R, Beato M. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650697&dopt=Abstract
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Confronting the hidden face of progesterone during the follicular phase. Author(s): de Ziegler D, Brioschi PA, Fanchin R, Bulletti C. Source: Journal of Assisted Reproduction and Genetics. 2003 January; 20(1): 29-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645865&dopt=Abstract
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Contact sites from human placental mitochondria: characterization and role in progesterone synthesis. Author(s): Uribe A, Strauss JF 3rd, Martinez F. Source: Archives of Biochemistry and Biophysics. 2003 May 15; 413(2): 172-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729614&dopt=Abstract
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Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China. Author(s): Wuu J, Hellerstein S, Lipworth L, Wide L, Xu B, Yu GP, Kuper H, Lagiou P, Hankinson SE, Ekbom A, Carlstrom K, Trichopoulos D, Adami HO, Hsieh CC. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 June; 11(3): 283-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131662&dopt=Abstract
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CP8668, a novel orally active nonsteroidal progesterone receptor modulator with tetrahydrobenzindolone skeleton. Author(s): Tabata Y, Iizuka Y, Shinei R, Kurihara K, Okonogi T, Hoshiko S, Kurata Y. Source: European Journal of Pharmacology. 2003 February 7; 461(1): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568918&dopt=Abstract
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Cyclic AMP and progesterone receptor cross-talk in human endometrium: a decidualizing affair. Author(s): Gellersen B, Brosens J. Source: The Journal of Endocrinology. 2003 September; 178(3): 357-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967329&dopt=Abstract
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Cyclo-oxygenase-2 (COX-2) mRNA expression correlates with progesterone receptor positivity in human breast cancer. Author(s): Singh-Ranger G, Kirkpatrick KL, Clark GM, Mokbel K. Source: Current Medical Research and Opinion. 2003; 19(2): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740157&dopt=Abstract
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Cyproterone, norethindrone, medroxyprogesterone and levonorgestrel are less potent local human growth hormone and insulin-like growth factor I secretion stimulators than progesterone in human breast cancer explants expressing the estrogen receptor. Author(s): Milewicz T, Kolodziejczyk J, Krzysiek J, Basta A, Sztefko K, Kurek S, Stachura J, Gregoraszczuk EL. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 August; 16(4): 319-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396561&dopt=Abstract
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Cytologic diagnosis of estrogen and progesterone receptors in breast imprints. Author(s): Sasaki M, Morimoto K, Koh M, Wakasa K, Haba T, Kinoshita H. Source: Acta Cytol. 2002 November-December; 46(6): 1056-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462082&dopt=Abstract
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Cytologic diagnosis of low grade endometrial stromal sarcoma by staining for estrogen and progesterone receptors. Author(s): Reich O, Pickel H, Regauer S. Source: Acta Cytol. 2002 July-August; 46(4): 790-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12146057&dopt=Abstract
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Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity. Author(s): Laureti S, Candeloro P, Aglietti MC, Giordano R, Arvat E, Ghigo E, Santeusanio F, Falorni A. Source: Clinical Endocrinology. 2002 November; 57(5): 677-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390344&dopt=Abstract
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Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male. Author(s): Brady BM, Anderson RA, Kinniburgh D, Baird DT. Source: Clinical Endocrinology. 2003 April; 58(4): 506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641635&dopt=Abstract
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Depomedroxyprogesterone acetate for hot flashes. Author(s): Barton D, Loprinzi C, Quella S, Sloan J, Pruthi S, Novotny P. Source: Journal of Pain and Symptom Management. 2002 December; 24(6): 603-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12551811&dopt=Abstract
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Difference of in vivo and in vitro antimineralocorticoid potency of progesterone. Author(s): Quinkler M, Diederich S. Source: Endocrine Research. 2002 November; 28(4): 465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530650&dopt=Abstract
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Differential activation of the IkappaBalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors. Author(s): Deroo BJ, Archer TK. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 August; 81(45): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361720&dopt=Abstract
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Differential amplification and overexpression of HER-2/neu, p53, MIB1, and estrogen receptor/progesterone receptor among medullary carcinoma, atypical medullary carcinoma, and high-grade invasive ductal carcinoma of breast. Author(s): Xu R, Feiner H, Li P, Yee H, Inghirami G, Delgado Y, Perle MA. Source: Archives of Pathology & Laboratory Medicine. 2003 November; 127(11): 1458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567723&dopt=Abstract
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Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors. Author(s): Akahira J, Suzuki T, Ito K, Kaneko C, Darnel AD, Moriya T, Okamura K, Yaegashi N, Sasano H. Source: Japanese Journal of Cancer Research : Gann. 2002 July; 93(7): 807-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149147&dopt=Abstract
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Differential regulation of secretory leukocyte protease inhibitor and elafin by progesterone. Author(s): King AE, Morgan K, Sallenave JM, Kelly RW. Source: Biochemical and Biophysical Research Communications. 2003 October 17; 310(2): 594-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14521952&dopt=Abstract
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Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. Author(s): Smid-Koopman E, Blok LJ, Kuhne LC, Burger CW, Helmerhorst TJ, Brinkmann AO, Huikeshoven FJ. Source: Journal of the Society for Gynecologic Investigation. 2003 January; 10(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517594&dopt=Abstract
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DNA aneuploidy in relation to the combination of analysis of estrogen receptor, progesterone receptor, p53 protein and epidermal growth factor receptor in 498 breast cancers. Author(s): Tsutsui S, Ohno S, Murakami S, Hachitanda Y, Oda S. Source: Oncology. 2002; 63(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187071&dopt=Abstract
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Do estrogen and progesterone play a role in the dry eye of Sjogren's syndrome? Author(s): Suzuki T, Schaumberg DA, Sullivan BD, Liu M, Richards SM, Sullivan RM, Dana MR, Sullivan DA. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 223-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114275&dopt=Abstract
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Does pre-treatment with micronized progesterone affect the ovarian response to a gonadotropin releasing hormone agonist flare-up protocol? Author(s): Loutradis D, Stefanidis K, Drakakis P, Kallianidis K, El Sheikh A, Milingos S, Siskos K, Michalas S. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2003 April; 17(2): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737670&dopt=Abstract
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Down-regulation of telomerase activity after progesterone treatment of human breast cancer cells: essential role of the cell cycle status. Author(s): Lebeau J, Fouchet P, Ory K, Chevillard S. Source: Anticancer Res. 2002 July-August; 22(4): 2161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174898&dopt=Abstract
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Effect of in vivo GnRH agonist and GnRH antagonist on hCG and insulin-stimulated progesterone production by human granulosa-lutein cells in vitro. Author(s): Mitwally MF, Casper RF. Source: Journal of Assisted Reproduction and Genetics. 2002 August; 19(8): 384-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182445&dopt=Abstract
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Effect of leptin on progesterone, human chorionic gonadotropin, and interleukin-6 secretion by human term trophoblast cells in culture. Author(s): Cameo P, Bischof P, Calvo JC. Source: Biology of Reproduction. 2003 February; 68(2): 472-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533410&dopt=Abstract
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Effect of medroxyprogesterone acetate on the efficiency of an oral protein-rich nutritional support in HIV-infected patients. Author(s): Rochon C, Prod'homme M, Laurichesse H, Tauveron I, Balage M, Gourdon F, Baud O, Jacomet C, Jouvency S, Bayle G, Champredon C, Thieblot P, Beytout J, Grizard J. Source: Reproduction, Nutrition, Development. 2003 March-April; 43(2): 203-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956319&dopt=Abstract
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Effect of medroxyprogesterone on arterial blood gases, leptin and neuropeptide Y in postmenopausal females. Author(s): Saaresranta T, Irjala K, Polo O. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1413-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503697&dopt=Abstract
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Effect of medroxyprogesterone on inspiratory flow shapes during sleep in postmenopausal women. Author(s): Saaresranta T, Aittokallio T, Polo-Kantola P, Helenius H, Polo O. Source: Respiratory Physiology & Neurobiology. 2003 March 3; 134(2): 131-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609480&dopt=Abstract
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Effect of progesterone combined with chemotherapy on epithelial ovarian cancer. Author(s): Chen X, Feng Y. Source: Chinese Medical Journal. 2003 March; 116(3): 388-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781043&dopt=Abstract
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Effect of raloxifene, 17beta-estradiol, and progesterone on mRNA for vascular endothelial growth factor isoforms 121 and 165 and thrombospondin-1 in Ishikawa cells. Author(s): Navarro FJ, Mirkin S, Archer DF. Source: Fertility and Sterility. 2003 June; 79(6): 1409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798890&dopt=Abstract
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Effect of short-term estrogen with and without progesterone therapy on circulating markers of endothelial activation and injury in postmenopausal women with unstable angina pectoris. Author(s): Chou ET, Schulman SP, Thiemann DR, Sohn RH, Bellantoni MF, Rade JJ. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745110&dopt=Abstract
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Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect. Author(s): Henmi H, Endo T, Kitajima Y, Manase K, Hata H, Kudo R. Source: Fertility and Sterility. 2003 August; 80(2): 459-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909517&dopt=Abstract
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Effects of estrogen and medroxyprogesterone acetate on subpopulations of triglyceride-rich lipoproteins and high-density lipoproteins. Author(s): Lamon-Fava S, Posfai B, Asztalos BF, Horvath KV, Dallal GE, Schaefer EJ. Source: Metabolism: Clinical and Experimental. 2003 October; 52(10): 1330-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564686&dopt=Abstract
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Effects of estrogen, progesterone, and combination exposure on interleukin-1 betainduced expression of VCAM-1, ICAM-1, PECAM, and E-selectin by human female iliac artery endothelial cells. Author(s): CMAJ. 2002 Aug 20;167(4):377-8 Source: The Journal of Surgical Research. 2002 June 15; 105(2): 215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12197697
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Effects of progesterone (P) and antiprogestin RU486 on LH and FSH release by incubated pituitaries from rats treated with the SERM LY11701 8-HCl and/or recombinant human FSH. Author(s): Bellido C, Aguilar R, Garrido-Gracia JC, Sanchez-Criado JE. Source: J Endocrinol Invest. 2002 September; 25(8): 702-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240902&dopt=Abstract
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Elevated progesterone: estradiol ratio--another test of ovarian reserve? Author(s): Younis JS. Source: Fertility and Sterility. 2003 September; 80(3): 679; Author Reply 679-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969737&dopt=Abstract
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Endometriosis-associated ovarian carcinoma: differential expression of vascular endothelial growth factor and estrogen/progesterone receptors. Author(s): Del Carmen MG, Smith Sehdev AE, Fader AN, Zahurak ML, Richardson M, Fruehauf JP, Montz FJ, Bristow RE. Source: Cancer. 2003 October 15; 98(8): 1658-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534882&dopt=Abstract
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Estradiol and progesterone regulate oxytocin receptor binding and expression in human breast cancer cell lines. Author(s): Amico JA, Rauk PN, Cai HM. Source: Endocrine. 2002 June; 18(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166628&dopt=Abstract
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Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women. Author(s): Hamada AL, Maruo T, Samoto T, Yoshida S, Nash H, Spitz IM, Johansson E. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2003 June; 17(3): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857433&dopt=Abstract
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Estrogen and progesterone as neuroprotective agents in the treatment of acute brain injuries. Author(s): Stein DG, Hoffman SW. Source: Pediatric Rehabilitation. 2003 January-March; 6(1): 13-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745891&dopt=Abstract
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Estrogen and progesterone modulate monocyte cell cycle progression and apoptosis. Author(s): Thongngarm T, Jenkins JK, Ndebele K, McMurray RW. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2003 March; 49(3): 129-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797519&dopt=Abstract
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Estrogen and progesterone receptor assay in paraffin-embedded breast cancer-reproducibility of assessment. Author(s): Chebil G, Bendahl PO, Ferno M; South Sweden Breast Cancer Group; North Sweden Breast Cancer Group. Source: Acta Oncologica (Stockholm, Sweden). 2003; 42(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665330&dopt=Abstract
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Estrogen and progesterone receptor expression in patients with uterine leiomyosarcoma and correlation with different clinicopathological parameters. Author(s): Bodner K, Bodner-Adler B, Kimberger O, Czerwenka K, Leodolter S, Mayerhofer K. Source: Anticancer Res. 2003 January-February; 23(1B): 729-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680175&dopt=Abstract
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Estrogen and progesterone receptor subtype expression in normal and malignant ovarian epithelial cell cultures. Author(s): Li AJ, Baldwin RL, Karlan BY. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 22-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861133&dopt=Abstract
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Estrogen and progesterone receptors in neoplastic and non-neoplastic thyroid lesions. Author(s): Lewy-Trenda I. Source: Pol J Pathol. 2002; 53(2): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140869&dopt=Abstract
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Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at King Chulalongkorn Memorial Hospital. Author(s): Lertsanguansinchai P, Chottetanaprasith T, Chatamra K, Sampatanukul P, Wannakrairot P, Rojpornpradit P, Shotelersuk K, Lertbutsayanukul C, Boonjunwetwat D, Vajragupta L. Source: J Med Assoc Thai. 2002 June; 85 Suppl 1: S193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188412&dopt=Abstract
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Estrogen and progesterone up-regulate glucose transporter expression in ZR-75-1 human breast cancer cells. Author(s): Medina RA, Meneses AM, Vera JC, Guzman C, Nualart F, Astuya A, de Los Angeles Garcia M, Kato S, Carvajal A, Pinto M, Owen GI. Source: Endocrinology. 2003 October; 144(10): 4527-35. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960090&dopt=Abstract
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Estrogen receptor alpha and activating protein-1 mediate estrogen responsiveness of the progesterone receptor gene in MCF-7 breast cancer cells. Author(s): Petz LN, Ziegler YS, Loven MA, Nardulli AM. Source: Endocrinology. 2002 December; 143(12): 4583-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446585&dopt=Abstract
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Estrogen receptor alpha and progesterone receptor A and B concentration and localization in the lower uterine segment in term parturition. Author(s): Winkler M, Kemp B, Classen-Linke I, Fischer DC, Zlatinsi S, Neulen J, Beier HM, Rath W. Source: Journal of the Society for Gynecologic Investigation. 2002 July-August; 9(4): 22632. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113882&dopt=Abstract
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Estrogen receptor-alpha mRNA in primary breast cancer: relationship to estrogen and progesterone receptor proteins and other prognostic factors. Author(s): Chearskul S, Bhothisuwan K, Churintrapun M, Semprasert N, Onreabroi S. Source: Asian Pac J Allergy Immunol. 2002 March; 20(1): 13-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125913&dopt=Abstract
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Expression and intracellular localization of progesterone receptors in cultured human gingival fibroblasts. Author(s): Kawahara K, Shimazu A. Source: Journal of Periodontal Research. 2003 June; 38(3): 242-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753360&dopt=Abstract
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Expression and transcriptional activity of progesterone receptor A and progesterone receptor B in mammalian cells. Author(s): Graham JD, Clarke CL. Source: Breast Cancer Research : Bcr. 2002; 4(5): 187-90. Epub 2002 July 02. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223122&dopt=Abstract
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Expression of a novel splicing variant deleting exons 4 and 6 of the progesterone receptor gene is a rare event in breast cancer. Author(s): Nagao K, Kohno N, Wakita K, Hikiji K, Yamamoto S, Hirata H, Hisatomi H. Source: Oncol Rep. 2003 March-April; 10(2): 305-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579263&dopt=Abstract
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Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors. Frequent expression of androgen receptor in a subset of malignant salivary gland tumors. Author(s): Nasser SM, Faquin WC, Dayal Y. Source: American Journal of Clinical Pathology. 2003 June; 119(6): 801-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817426&dopt=Abstract
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Expression of estrogen receptor (ER) (beta)cx protein in ER(alpha)-positive breast cancer: specific correlation with progesterone receptor. Author(s): Saji S, Omoto Y, Shimizu C, Warner M, Hayashi Y, Horiguchi S, Watanabe T, Hayashi S, Gustafsson JA, Toi M. Source: Cancer Research. 2002 September 1; 62(17): 4849-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208729&dopt=Abstract
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Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue. Author(s): Smith RA, Lea RA, Curran JE, Weinstein SR, Griffiths LR. Source: Breast Cancer Research : Bcr. 2003; 5(1): R9-12. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559052&dopt=Abstract
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Expression of progesterone receptors A and B and insulin-like growth factor-I in human myometrium and fibroids after treatment with a gonadotropin-releasing hormone analogue. Author(s): Wu X, Wang H, Englund K, Blanck A, Lindblom B, Sahlin L. Source: Fertility and Sterility. 2002 November; 78(5): 985-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413982&dopt=Abstract
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Expression of the progesterone receptor and progesterone- metabolising enzymes in the female and male human kidney. Author(s): Bumke-Vogt C, Bahr V, Diederich S, Herrmann SM, Anagnostopoulos I, Oelkers W, Quinkler M. Source: The Journal of Endocrinology. 2002 November; 175(2): 349-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429033&dopt=Abstract
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Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease. Author(s): Fenton SL, Luong QT, Sarafeim A, Mustard KJ, Pound J, Desmond JC, Gordon J, Drayson MT, Bunce CM. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 March; 17(3): 568-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646946&dopt=Abstract
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Functional properties of the N-terminal region of progesterone receptors and their mechanistic relationship to structure. Author(s): Takimoto GS, Tung L, Abdel-Hafiz H, Abel MG, Sartorius CA, Richer JK, Jacobsen BM, Bain DL, Horwitz KB. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 June; 85(2-5): 209-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943706&dopt=Abstract
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GABA receptors, progesterone and premenstrual dysphoric disorder. Author(s): Sundstrom Poromaa I, Smith S, Gulinello M. Source: Archives of Women's Mental Health. 2003 February; 6(1): 23-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715262&dopt=Abstract
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Growth effects of raloxifene, estradiol, medroxy-progesterone acetate, and progesterone on human endometrial adenocarcinoma cells. Author(s): Boostanfar R, Amezcua CA, Tourgeman DE, Roy S, Felix JC, Stanczyk FZ. Source: Fertility and Sterility. 2003 January; 79(1): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524096&dopt=Abstract
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Growth inhibition of MCF-7 human breast cancer cells by progesterone is associated with cell differentiation and phosphorylation of Akt protein. Author(s): Alkhalaf M, El-Mowafy A, Karam S. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 2002 October; 11(5): 481-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394246&dopt=Abstract
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HDLG5/KIAA0583, encoding a MAGUK-family protein, is a primary progesterone target gene in breast cancer cells. Author(s): Purmonen S, Ahola TM, Pennanen P, Aksenov N, Zhuang YH, Tuohimaa P, Ylikomi T. Source: International Journal of Cancer. Journal International Du Cancer. 2002 November 1; 102(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353226&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529413&dopt=Abstract
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Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-alpha and transforming growth factor-beta 1 output. Author(s): Zicari A, Ticconi C, Realacci M, Cela O, Santangelo C, Pietropolli A, Russo MA, Piccione E. Source: Journal of Reproductive Immunology. 2002 July-August; 56(1-2): 123-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106888&dopt=Abstract
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How oestrogen or progesterone might change a woman's susceptibility to HIV-1 infection. Author(s): Mingjia L, Short R. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 November; 42(5): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495087&dopt=Abstract
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Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles. Author(s): Fujimoto A, Osuga Y, Fujiwara T, Yano T, Tsutsumi O, Momoeda M, Kugu K, Koga K, Morita Y, Wada O, Taketani Y. Source: Journal of Assisted Reproduction and Genetics. 2002 December; 19(12): 550-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503886&dopt=Abstract
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Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization. Author(s): Cramer DW, Hornstein MD, McShane P, Powers RD, Lescault PJ, Vitonis AF, De Vivo I. Source: American Journal of Obstetrics and Gynecology. 2003 October; 189(4): 1085-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586360&dopt=Abstract
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Identification of estrogen and progesterone receptor mRNA expression in the conjunctiva of premenopausal women. Author(s): Fuchsjager-Mayrl G, Nepp J, Schneeberger C, Sator M, Dietrich W, Wedrich A, Huber J, Tschugguel W. Source: Investigative Ophthalmology & Visual Science. 2002 September; 43(9): 2841-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202500&dopt=Abstract
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Immunohistochemical analysis of 1,25-dihydroxyvitamin-D3-receptors, estrogen and progesterone receptors and Ki-67 in ovarian carcinoma. Author(s): Villena-Heinsen C, Meyberg R, Axt-Fliedner R, Reitnauer K, Reichrath J, Friedrich M. Source: Anticancer Res. 2002 July-August; 22(4): 2261-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174912&dopt=Abstract
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Immunohistochemical detection of progesterone receptors and the correlation with Ki-67 labeling indices in paraffin-embedded sections of meningiomas. Author(s): Gursan N, Gundogdu C, Albayrak A, Kabalar ME. Source: The International Journal of Neuroscience. 2002 April; 112(4): 463-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12325398&dopt=Abstract
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Immunohistochemical expression of heat shock protein 27, in normal hyperplastic and neoplastic endometrium: correlation with estrogen and progesterone receptor status, p53, pRb and proliferation associated indices (PCNA, MIB1). Author(s): Zagorianakou N, Ioachim E, Mitselou A, Kitsou E, Zagorianakou P, Makrydimas G, Salmas M, Agnantis NJ. Source: Eur J Gynaecol Oncol. 2003; 24(3-4): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807244&dopt=Abstract
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Improved continuation rate of depot-medroxyprogesterone acetate in adolescent mothers. Author(s): Omar H, Fowler A, D'Angelo S. Source: Int J Adolesc Med Health. 2002 April-June; 14(2): 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467187&dopt=Abstract
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In vitro and in vivo characterization of novel nonsteroidal progesterone receptor antagonists derived from the fungal metabolite PF1092C. Author(s): Tabata Y, Iizuka Y, Masuda NT, Shinei R, Kurihara K, Okonogi T, Hoshiko S, Kurata Y. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 October; 82(23): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477488&dopt=Abstract
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Increased endogenous level of melatonin in preovulatory human follicles does not directly influence progesterone production. Author(s): Nakamura Y, Tamura H, Takayama H, Kato H. Source: Fertility and Sterility. 2003 October; 80(4): 1012-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556825&dopt=Abstract
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Influence of progesterone and clomiphene on Tolosa-Hunt syndrome. Author(s): Levin N, Karussis D. Source: Neurology. 2002 November 26; 59(10): 1661-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451225&dopt=Abstract
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Infusion of epinephrine decreases serum levels of cortisol and 17hydroxyprogesterone in patients with rheumatoid arthritis. Author(s): Straub RH, Kittner JM, Heijnen C, Schedlowski M, Schmidt RE, Jacobs R. Source: The Journal of Rheumatology. 2002 August; 29(8): 1659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180725&dopt=Abstract
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Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors. Author(s): Rhodes ME, Frye CA. Source: Cognitive, Affective & Behavioral Neuroscience. 2001 September; 1(3): 287-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467128&dopt=Abstract
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Inhibition of progesterone secretion by oestradiol administered in the luteal phase of assisted conception cycles. Author(s): Tay PY, Lenton EA. Source: Med J Malaysia. 2003 June; 58(2): 187-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14569738&dopt=Abstract
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Inhibition of progesterone-induced VEGF production in human breast cancer cells by the pure antiestrogen ICI 182,780. Author(s): Hyder SM, Stancel GM. Source: Cancer Letters. 2002 July 8; 181(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430178&dopt=Abstract
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Inhibitory effects of progesterone on plasma membrane fluidity and tumorigenic potential of ovarian epithelial cancer cells. Author(s): McDonnel AC, Van Kirk EA, Isaak DD, Murdoch WJ. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 March; 228(3): 30814. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626776&dopt=Abstract
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Inter-ictal and post-ictal circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in epileptic children. Author(s): Grosso S, Luisi S, Mostardini R, Farnetani M, Cobellis L, Morgese G, Balestri P, Petraglia F. Source: Epilepsy Research. 2003 April; 54(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742593&dopt=Abstract
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Interleukin-1 beta stimulates progesterone production by in vitro human luteal cells: evidence of a mediatory role of prostaglandins. Author(s): Miceli F, Tropea A, Minici F, Navarra P, Lanzone A, Apa R. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2690-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788874&dopt=Abstract
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Interleukin-2, interferon-alpha and medroxyprogesterone acetate in metastatic renal cell carcinoma. Author(s): Naglieri E, Lopez M, Lelli G, Morelli F, Amodio A, Di Tonno P, Gebbia N, Di Seri M, Chetri MC, Rizzo P, Abbate I, Casamassima A, Selvaggi FP, Colucci G. Source: Anticancer Res. 2002 September-October; 22(5): 3045-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530040&dopt=Abstract
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Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study. Author(s): Bertelli G, Venturini M, Del Mastro L, Bergaglio M, Sismondi P, Biglia N, Venturini S, Porcile G, Pronzato P, Costantini M, Rosso R. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 June; 13(6): 883-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123333&dopt=Abstract
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Jun dimerization protein 2 functions as a progesterone receptor N-terminal domain coactivator. Author(s): Wardell SE, Boonyaratanakornkit V, Adelman JS, Aronheim A, Edwards DP. Source: Molecular and Cellular Biology. 2002 August; 22(15): 5451-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101239&dopt=Abstract
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Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance. Author(s): Wakatsuki A, Okatani Y, Fukaya T. Source: Circulation. 2003 May 27; 107(20): E197; Author Reply E197. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777328&dopt=Abstract
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Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance. Author(s): Kaunitz AM. Source: Circulation. 2003 March 11; 107(9): E67-8; Author Reply E67-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628963&dopt=Abstract
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Long-term use of contraceptive depot medroxyprogesterone acetate in young women impairs arterial endothelial function assessed by cardiovascular magnetic resonance. Author(s): Sorensen MB, Collins P, Ong PJ, Webb CM, Hayward CS, Asbury EA, Gatehouse PD, Elkington AG, Yang GZ, Kubba A, Pennell DJ. Source: Circulation. 2002 September 24; 106(13): 1646-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270857&dopt=Abstract
Studies
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Loss of progesterone receptor may lead to an invasive phenotype in human endometrial cancer. Author(s): Hanekamp EE, Kuhne EC, Smid-Koopman E, de Ruiter PE, Chadha-Ajwani S, Brinkmann AO, Burger CW, Grootegoed JA, Huikeshoven FJ, Blok LJ. Source: European Journal of Cancer (Oxford, England : 1990). 2002 November; 38 Suppl 6: S71-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409083&dopt=Abstract
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MAP kinases couple multiple functions of human progesterone receptors: degradation, transcriptional synergy, and nuclear association. Author(s): Qiu M, Lange CA. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 June; 85(2-5): 147-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943699&dopt=Abstract
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Mechanism of action of progesterone antagonists. Author(s): Leonhardt SA, Edwards DP. Source: Experimental Biology and Medicine (Maywood, N.J.). 2002 December; 227(11): 969-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486206&dopt=Abstract
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Mechanism of cortisol/progesterone antagonism in the regulation of 15hydroxyprostaglandin dehydrogenase activity and messenger ribonucleic acid levels in human chorion and placental trophoblast cells at term. Author(s): Patel FA, Funder JW, Challis JR. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2922-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788907&dopt=Abstract
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Medroxyprogesterone acetate treatment of abnormal uterine bleeding: factors predicting satisfaction. Author(s): Richter HE, Learman LA, Lin F, Varner RE, Hendrix SL, Summitt RL, Washington AE. Source: American Journal of Obstetrics and Gynecology. 2003 July; 189(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861135&dopt=Abstract
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Membrane-bound progesterone receptor expression in human aortic endothelial cells. Author(s): Welter BH, Hansen EL, Saner KJ, Wei Y, Price TM. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 August; 51(8): 1049-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871986&dopt=Abstract
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Membrane-bound progesterone receptors contain a cytochrome b5-like ligandbinding domain. Author(s): Mifsud W, Bateman A. Source: Genome Biology. 2002; 3(12): Research0068. Epub 2002 November 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537557&dopt=Abstract
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Myolipoma of soft tissue: an unusual tumor with expression of estrogen and progesterone receptors. Report of two cases and review of the literature. Author(s): Fernandez-Aguilar S, Saint-Aubain N, Dargent JL, Fayt I, Noel JC. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 November; 81(11): 1088-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421182&dopt=Abstract
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Natural history of estrogen receptor-negative, progesterone receptor-positive breast cancer. Author(s): Nikolic-Vukosavljevic D, Kanjer K, Neskovic-Konstantinovic Z, Vukotic D. Source: Int J Biol Markers. 2002 July-September; 17(3): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408471&dopt=Abstract
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Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study. Author(s): Lagiou P, Tamimi R, Mucci LA, Trichopoulos D, Adami HO, Hsieh CC. Source: Obstetrics and Gynecology. 2003 April; 101(4): 639-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681864&dopt=Abstract
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New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles. Author(s): Fensome A, Bender R, Cohen J, Collins MA, Mackner VA, Miller LL, Ullrich JW, Winneker R, Wrobel J, Zhang P, Zhang Z, Zhu Y. Source: Bioorganic & Medicinal Chemistry Letters. 2002 December 2; 12(23): 3487-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419390&dopt=Abstract
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No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina. Author(s): Lancaster JM, Wenham RM, Halabi S, Calingaert B, Marks JR, Moorman PG, Bentley RC, Berchuck A, Schildkraut JM. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2003 March; 12(3): 226-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646513&dopt=Abstract
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Non-classical 21-hydroxylase deficiency in children: association of adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of compound heterozygosity with severe mutations. Author(s): Cleve Clin J Med. 2002 Sep;69(9):680-1 Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(8): 892-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222971
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Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues. Author(s): Bramley T. Source: Reproduction (Cambridge, England). 2003 January; 125(1): 3-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622691&dopt=Abstract
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Norelgestromin as selective estrogen enzyme modulator in human breast cancer cell lines. Effect on sulfatase activity in comparison to medroxyprogesterone acetate. Author(s): Pasqualini JR, Caubel P, Friedman AJ, Philippe JC, Chetrite GS. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 February; 84(23): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711003&dopt=Abstract
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Novel 5-aryl-1,3-dihydro-indole-2-thiones. potent, orally active progesterone receptor agonists. Author(s): Fensome A, Koko M, Wrobel J, Zhang P, Zhang Z, Cohen J, Lundeen S, Rudnick K, Zhu Y, Winneker R. Source: Bioorganic & Medicinal Chemistry Letters. 2003 April 7; 13(7): 1317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657272&dopt=Abstract
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Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues. Author(s): Hisatomi H, Kohno N, Wakita K, Nagao K, Hirata H, Hikiji K, Harada S. Source: International Journal of Cancer. Journal International Du Cancer. 2003 June 10; 105(2): 182-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673676&dopt=Abstract
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Oestrogen and progesterone receptor expression influences DNA ploidy and the proliferation potential of breast cancer cells. Author(s): Andronas M, Dlay SS, Sherbet GV. Source: Anticancer Res. 2003 May-June; 23(3C): 3029-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926157&dopt=Abstract
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Ovarian carcinoma of hypercalcemic type: myoid features and lack of estrogen and progesterone receptors. Author(s): Zamecnik M, Michal M. Source: Virchows Archiv : an International Journal of Pathology. 2003 February; 442(2): 186-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680415&dopt=Abstract
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Overexpression of mdm2 and p53 and association with progesterone receptor expression in benign meningiomas. Author(s): Das A, Tan WL, Teo J, Smith DR. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2002 September; 22(3): 194-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416559&dopt=Abstract
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Overexpression of wild-type p53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone. Author(s): Alkhalaf M, El-Mowafy AM. Source: The Journal of Endocrinology. 2003 October; 179(1): 55-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529565&dopt=Abstract
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Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. Author(s): Wren BG, Day RO, McLachlan AJ, Williams KM. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 104-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841880&dopt=Abstract
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Pharmacologic doses of medroxyprogesterone may cause bone loss through glucocorticoid activity: an hypothesis. Author(s): Ishida Y, Ishida Y, Heersche JN. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2002 August; 13(8): 601-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181616&dopt=Abstract
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Possible involvement of hypersecretion of progesterone from an adrenal adenoma without androgen excess in primary amenorrhea. Author(s): Nishikawa T. Source: Intern Med. 2002 November; 41(11): 912. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487155&dopt=Abstract
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Post-abortion depot medroxyprogesterone acetate continuation rates: a randomized trial of cyclic estradiol. Author(s): Goldberg AB, Cardenas LH, Hubbard AE, Darney PD. Source: Contraception. 2002 October; 66(4): 215-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413614&dopt=Abstract
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Pregnancy estriol, estradiol, progesterone and prolactin in relation to birth weight and other birth size variables (United States). Author(s): Mucci LA, Lagiou P, Tamimi RM, Hsieh CC, Adami HO, Trichopoulos D. Source: Cancer Causes & Control : Ccc. 2003 May; 14(4): 311-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846361&dopt=Abstract
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Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. Author(s): Brancazio LR, Murtha AP, Heine RP. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1087-8; Author Reply 1087-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968095&dopt=Abstract
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Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. Author(s): Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Source: The New England Journal of Medicine. 2003 June 12; 348(24): 2379-85. Erratum In: N Engl J Med. 2003 September 25; 349(13): 1299. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802023&dopt=Abstract
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Progesterone activates fatty acid amide hydrolase (FAAH) promoter in human T lymphocytes through the transcription factor Ikaros. Evidence for a synergistic effect of leptin. Author(s): Maccarrone M, Bari M, Di Rienzo M, Finazzi-Agro A, Rossi A. Source: The Journal of Biological Chemistry. 2003 August 29; 278(35): 32726-32. Epub 2003 June 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799380&dopt=Abstract
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Progesterone and glucocorticoid receptors recruit distinct coactivator complexes and promote distinct patterns of local chromatin modification. Author(s): Li X, Wong J, Tsai SY, Tsai MJ, O'Malley BW. Source: Molecular and Cellular Biology. 2003 June; 23(11): 3763-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748280&dopt=Abstract
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Progesterone and preterm delivery--deja vu all over again. Author(s): Greene MF. Source: The New England Journal of Medicine. 2003 June 12; 348(24): 2453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802032&dopt=Abstract
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Progesterone as a mediator of gonadotrophin action in the corpus luteum: beyond steroidogenesis. Author(s): Stouffer RL. Source: Human Reproduction Update. 2003 March-April; 9(2): 99-117. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751773&dopt=Abstract
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Progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate. Author(s): Dart R, Ramanujam P, Dart L. Source: The American Journal of Emergency Medicine. 2002 November; 20(7): 575-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442232&dopt=Abstract
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Progesterone as a regulator of granulosa cell viability. Author(s): Peluso JJ. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2003 June; 85(2-5): 167-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943701&dopt=Abstract
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Progesterone crosstalks with insulin-like growth factor signaling in breast cancer cells via induction of insulin receptor substrate-2. Author(s): Cui X, Lazard Z, Zhang P, Hopp TA, Lee AV. Source: Oncogene. 2003 October 9; 22(44): 6937-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534541&dopt=Abstract
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Progesterone effects during sequential hormone replacement therapy. Author(s): Andreen L, Bixo M, Nyberg S, Sundstrom-Poromaa I, Backstrom T. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 571-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720542&dopt=Abstract
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Progesterone in gestational diabetes mellitus: guilty or not guilty? Author(s): Branisteanu DD, Mathieu C. Source: Trends in Endocrinology and Metabolism: Tem. 2003 March; 14(2): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591170&dopt=Abstract
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Progesterone increase under DHEA-substitution in males. Author(s): Nadjafi-Triebsch C, Huell M, Burki D, Rohr UD. Source: Maturitas. 2003 July 25; 45(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818469&dopt=Abstract
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Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity. Author(s): Laskarin G, Tokmadzic VS, Strbo N, Bogovic T, Szekeres-Bartho J, Randic L, Podack ER, Rukavina D. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2002 October; 48(4): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516630&dopt=Abstract
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Progesterone induces cellular differentiation in MDA-MB-231 breast cancer cells transfected with progesterone receptor complementary DNA. Author(s): Lin VC, Jin R, Tan PH, Aw SE, Woon CT, Bay BH. Source: American Journal of Pathology. 2003 June; 162(6): 1781-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759236&dopt=Abstract
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Progesterone induces the proliferation of urothelial cells in an epidermal growth factor dependent manner. Author(s): Teng J, Wang ZY, Bjorling DE. Source: The Journal of Urology. 2003 November; 170(5): 2014-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532844&dopt=Abstract
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Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations. Author(s): Carmody BJ, Arora S, Wakefield MC, Weber M, Fox CJ, Sidawy AN. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 October; 36(4): 833-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368746&dopt=Abstract
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Progesterone metabolism in human leukemic monoblast U937 cells. Author(s): Suzuki T, Murry BA, Darnel AD, Sasano H. Source: Endocrine Journal. 2002 October; 49(5): 539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507272&dopt=Abstract
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Progesterone production and actions in the human central nervous system and neurogenic tumors. Author(s): Inoue T, Akahira J, Suzuki T, Darnel AD, Kaneko C, Takahashi K, Hatori M, Shirane R, Kumabe T, Kurokawa Y, Satomi S, Sasano H. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 5325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414909&dopt=Abstract
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Progesterone receptor as an indicator of sperm function. Author(s): Gadkar S, Shah CA, Sachdeva G, Samant U, Puri CP. Source: Biology of Reproduction. 2002 October; 67(4): 1327-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297552&dopt=Abstract
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Progesterone receptor expression in angioleiomyoma of the nasal cavity. Author(s): Marioni G, Marchese-Ragona R, Fernandez S, Bruzon J, Marino F, Staffieri A. Source: Acta Oto-Laryngologica. 2002 June; 122(4): 408-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125998&dopt=Abstract
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Progesterone receptor expression in neurofibromas. Author(s): McLaughlin ME, Jacks T. Source: Cancer Research. 2003 February 15; 63(4): 752-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591720&dopt=Abstract
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Progesterone receptor interacting coregulatory proteins and cross talk with cell signaling pathways. Author(s): Edwards DP, Wardell SE, Boonyaratanakornkit V. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 December; 83(1-5): 173-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650714&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684155&dopt=Abstract
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Progesterone receptor mRNA variant containing novel exon insertions between exon 4 and exon 5 in human uterine endometrium. Author(s): Yamanaka T, Hirata S, Shoda T, Hoshi K. Source: Endocrine Journal. 2002 August; 49(4): 473-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402980&dopt=Abstract
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Progesterone receptor quantification as a strong prognostic determinant in postmenopausal breast cancer women under tamoxifen therapy. Author(s): Lamy PJ, Pujol P, Thezenas S, Kramar A, Rouanet P, Guilleux F, Grenier J. Source: Breast Cancer Research and Treatment. 2002 November; 76(1): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408377&dopt=Abstract
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Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. Author(s): Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 15; 21(10): 1973-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743151&dopt=Abstract
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Progesterone receptor-positive eruptive syringoma associated with diabetes. Author(s): Timpanidis PC, Lakhani SR, Groves RW. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5 Suppl): S1034. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734492&dopt=Abstract
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Progesterone receptor-regulated gene networks in implantation. Author(s): Bagchi IC, Cheon YP, Li Q, Bagchi MK. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 September 1; 8: S85261. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957875&dopt=Abstract
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Progesterone receptors - animal models and cell signaling in breast cancer: Role of steroid receptor coactivators and corepressors of progesterone receptors in breast cancer. Author(s): Gao X, Nawaz Z. Source: Breast Cancer Research : Bcr. 2002; 4(5): 182-6. Epub 2002 June 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223121&dopt=Abstract
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Progesterone receptors A and B differentially affect the growth of estrogendependent human breast tumor xenografts. Author(s): Sartorius CA, Shen T, Horwitz KB. Source: Breast Cancer Research and Treatment. 2003 June; 79(3): 287-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846413&dopt=Abstract
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Progesterone receptors--animal models and cell signalling in breast cancer. Diverse activation pathways for the progesterone receptor: possible implications for breast biology and cancer. Author(s): Lanari C, Molinolo AA. Source: Breast Cancer Research : Bcr. 2002; 4(6): 240-3. Epub 2002 September 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473170&dopt=Abstract
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Progesterone receptors--animal models and cell signalling in breast cancer. Implications for breast cancer of inclusion of progestins in hormone replacement therapies. Author(s): Schairer C. Source: Breast Cancer Research : Bcr. 2002; 4(6): 244-8. Epub 2002 October 07. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473171&dopt=Abstract
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Progesterone regulates IL12 expression in pregnancy lymphocytes by inhibiting phospholipase A2. Author(s): Par G, Geli J, Kozma N, Varga P, Szekeres-Bartho J. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2003 January; 49(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733588&dopt=Abstract
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Progesterone skin cream and measurements of absorption. Author(s): Gambrell RD Jr. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544669&dopt=Abstract
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Progesterone upregulates GATA-1 on erythroid progenitors cells in liquid culture. Author(s): da Silva Santos Duarte A, Sales TS, Mengel JO, Costa FF, Saad ST. Source: Blood Cells, Molecules & Diseases. 2002 September-October; 29(2): 213-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490288&dopt=Abstract
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Progesterone upregulates TGF-b isoforms (b1, b2, and b3) expression in normal human osteoblast-like cells. Author(s): Luo XH, Liao EY, Su X. Source: Calcified Tissue International. 2002 October; 71(4): 329-34. Epub 2002 August 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154395&dopt=Abstract
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Progesterone, neurosteroids, and the hormonal basis of catamenial epilepsy. Author(s): Rogawski MA. Source: Annals of Neurology. 2003 March; 53(3): 288-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601696&dopt=Abstract
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Progesterone: a novel adjunct to intravesical chemotherapy. Author(s): Lewin J, Cooper A, Birch B. Source: Bju International. 2002 November; 90(7): 736-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410758&dopt=Abstract
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Progesterone-induced apoptosis in immortalized normal and malignant human ovarian surface epithelial cells involves enhanced expression of FasL. Author(s): Syed V, Ho SM. Source: Oncogene. 2003 October 9; 22(44): 6883-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534535&dopt=Abstract
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Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Author(s): da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 419-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592250&dopt=Abstract
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Quality assurance for detection of estrogen and progesterone receptors by immunohistochemistry in Austrian pathology laboratories. Author(s): Regitnig P, Reiner A, Dinges HP, Hofler G, Muller-Holzner E, Lax SF, Obrist P, Rudas M, Quehenberger F. Source: Virchows Archiv : an International Journal of Pathology. 2002 October; 441(4): 328-34. Epub 2002 September 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404057&dopt=Abstract
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Quantitation of estradiol receptors alpha and beta and progesterone receptors in human breast tumors by real-time reverse transcription-polymerase chain reaction. Correlation with protein assays. Author(s): de Cremoux P, Tran-Perennou C, Elie C, Boudou E, Barbaroux C, Poupon MF, De Rycke Y, Asselain B, Magdelenat H. Source: Biochemical Pharmacology. 2002 August 1; 64(3): 507-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147303&dopt=Abstract
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Quantitative fluorescence cytometric measurement of estrogen and progesterone receptors: correlation with the hormone binding assay. Author(s): Gritzapis AD, Baxevanis CN, Missitzis I, Katsanou ES, Alexis MN, Yotis J, Papamichail M. Source: Breast Cancer Research and Treatment. 2003 July; 80(1): 1-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889594&dopt=Abstract
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Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups. Author(s): Chu KC, Anderson WF. Source: Breast Cancer Research and Treatment. 2002 June; 74(3): 199-211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206512&dopt=Abstract
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Reduced vaginal bleeding in postmenopausal women who receive combined norethindrone acetate and low-dose ethinyl estradiol therapy versus combined conjugated equine estrogens and medroxyprogesterone acetate therapy. Author(s): Simon JA, Liu JH, Speroff L, Shumel BS, Symons JP. Source: American Journal of Obstetrics and Gynecology. 2003 January; 188(1): 92-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548201&dopt=Abstract
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Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in neonates, children and young adults. Author(s): Elmlinger MW, Kuhnel W, Ranke MB. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 November; 40(11): 1151-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521235&dopt=Abstract
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Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases. Author(s): Cornet PB, Picquet C, Lemoine P, Osteen KG, Bruner-Tran KL, Tabibzadeh S, Courtoy PJ, Eeckhout Y, Marbaix E, Henriet P. Source: The Journal of Biological Chemistry. 2002 November 8; 277(45): 42496-504. Epub 2002 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215426&dopt=Abstract
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Regulation of exercise carbohydrate metabolism by estrogen and progesterone in women. Author(s): D'Eon TM, Sharoff C, Chipkin SR, Grow D, Ruby BC, Braun B. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 November; 283(5): E1046-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376334&dopt=Abstract
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Regulation of human endometrial transforming growth factor beta1 and beta3 isoforms through menstrual cycle and medroxyprogesterone acetate treatment. Author(s): Reis FM, Ribeiro MF, Maia AL, Spritzer PM. Source: Histology and Histopathology. 2002; 17(3): 739-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168782&dopt=Abstract
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Regulation of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP, and progesterone secretion in luteinized granulosa cells from normally ovulating women with polycystic ovary disease. Author(s): Ben-Shlomo I, Goldman S, Shalev E. Source: Fertility and Sterility. 2003 March; 79 Suppl 1: 694-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620479&dopt=Abstract
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Regulation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression by estradiol and progesterone in human endometrium. Author(s): Guzeloglu-Kayisli O, Kayisli UA, Al-Rejjal R, Zheng W, Luleci G, Arici A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 October; 88(10): 5017-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557489&dopt=Abstract
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Relationship between progesterone receptor level in endometrium and bleeding pattern in depot medroxyprogesterone acetate users. Author(s): Chotnopparatpattara P, Taneepanichskul S, Treratanachat S, Charuruks N. Source: J Med Assoc Thai. 2003 February; 86(2): 172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678156&dopt=Abstract
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Relative binding activity of new antigestagens with progesterone receptors in human hyperplastic endometrium. Author(s): Kamernitskii AV, Levina IS, Kareva EN, Kirpichnikova NV, Mgdesyan KK, Ovchinnikova EV. Source: Bulletin of Experimental Biology and Medicine. 2002 November; 134(5): 445-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802447&dopt=Abstract
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Renal inactivation, mineralocorticoid generation, and 11beta-hydroxysteroid dehydrogenase inhibition ameliorate the antimineralocorticoid effect of progesterone in vivo. Author(s): Quinkler M, Meyer B, Oelkers W, Diederich S. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3767-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915667&dopt=Abstract
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Repressors of androgen and progesterone receptor action. Author(s): Agoulnik IU, Krause WC, Bingman WE 3rd, Rahman HT, Amrikachi M, Ayala GE, Weigel NL. Source: The Journal of Biological Chemistry. 2003 August 15; 278(33): 31136-48. Epub 2003 May 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771131&dopt=Abstract
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Risk of breast cancer classified by joint estrogen receptor and progesterone receptor status among women 20-44 years of age. Author(s): Britton JA, Gammon MD, Schoenberg JB, Stanford JL, Coates RJ, Swanson CA, Potischman N, Malone KE, Brogan DJ, Daling JR, Brinton LA. Source: American Journal of Epidemiology. 2002 September 15; 156(6): 507-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225998&dopt=Abstract
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Role of progesterone antagonists and new selective progesterone receptor modulators in reproductive health. Author(s): Olive DL. Source: Obstetrical & Gynecological Survey. 2002 November; 57(11 Suppl 4): S55-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454529&dopt=Abstract
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Role of progesterone in structural and biochemical remodeling of endometrium. Author(s): Rosario G, Sachdeva G, Okulicz WC, Ace CI, Katkam RR, Puri CP. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 September 1; 8: S92435. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957856&dopt=Abstract
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Seizure exacerbation associated with inhibition of progesterone metabolism. Author(s): Herzog AG, Frye CA. Source: Annals of Neurology. 2003 March; 53(3): 390-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601707&dopt=Abstract
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Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Author(s): Higaki Y, Usami N, Shintani S, Ishikura S, El-Kabbani O, Hara A. Source: Chemico-Biological Interactions. 2003 February 1; 143-144: 503-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604236&dopt=Abstract
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Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells. Author(s): Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC. Source: The Journal of Biological Chemistry. 2003 June 13; 278(24): 21474-82. Epub 2003 April 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672823&dopt=Abstract
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Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women. Author(s): Muttukrishna S, Sharma S, Barlow DH, Ledger W, Groome N, Sathanandan M. Source: Human Reproduction (Oxford, England). 2002 October; 17(10): 2535-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351524&dopt=Abstract
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Sex-specific alterations in neutrophil apoptosis: the role of estradiol and progesterone. Author(s): Molloy EJ, O'Neill AJ, Grantham JJ, Sheridan-Pereira M, Fitzpatrick JM, Webb DW, Watson RW. Source: Blood. 2003 October 1; 102(7): 2653-9. Epub 2003 June 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791649&dopt=Abstract
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Solar urticaria due to progesterone compounds in oral contraceptives. Author(s): Morison WL. Source: Photodermatology, Photoimmunology & Photomedicine. 2003 June; 19(3): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914601&dopt=Abstract
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Sperm binding to the human zona pellucida and calcium influx in response to GnRH and progesterone. Author(s): Morales P, Pizarro E, Kong M, Pasten C. Source: Andrologia. 2002 October; 34(5): 301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390088&dopt=Abstract
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Stimulation of voltage-dependent calcium channels during capacitation and by progesterone in human sperm. Author(s): Gonzalez-Martinez MT, Bonilla-Hernandez MA, Guzman-Grenfell AM. Source: Archives of Biochemistry and Biophysics. 2002 December 15; 408(2): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464273&dopt=Abstract
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Structure-function relationships of rat liver CYP3A9 to its human liver orthologs: sitedirected active site mutagenesis to a progesterone dihydroxylase. Author(s): Xue L, Zgoda VG, Arison B, Almira Correia M. Source: Archives of Biochemistry and Biophysics. 2003 January 1; 409(1): 113-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464250&dopt=Abstract
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Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC1. Author(s): Chauchereau A, Amazit L, Quesne M, Guiochon-Mantel A, Milgrom E. Source: The Journal of Biological Chemistry. 2003 April 4; 278(14): 12335-43. Epub 2003 January 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529333&dopt=Abstract
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Supplemental progesterone to prevent preterm birth. Author(s): Iams JD. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592229&dopt=Abstract
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Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation. Author(s): Tsuda K, Kinoshita Y, Nishio I. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 August; 15(8): 702-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160193&dopt=Abstract
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The antiinflammatory properties of medroxyprogesterone acetate. Author(s): Rachon D. Source: Circulation. 2002 November 26; 106(22): E185; Author Reply E185. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451020&dopt=Abstract
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The correlation between the response to progestogen treatment and the expression of progesterone receptor B and 17beta-hydroxysteroid dehydrogenase type 2 in human endometrial carcinoma. Author(s): Utsunomiya H, Suzuki T, Ito K, Moriya T, Konno R, Sato S, Yaegashi N, Okamura K, Sasano H. Source: Clinical Endocrinology. 2003 June; 58(6): 696-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780745&dopt=Abstract
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The correlations between estradiol, estrone, estriol, progesterone, and sex hormonebinding globulin and anterior cruciate ligament stiffness in healthy, active females. Author(s): Romani W, Patrie J, Curl LA, Flaws JA. Source: Journal of Women's Health (2002). 2003 April; 12(3): 287-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804359&dopt=Abstract
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The differential expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67 in endometrial polyps. Author(s): Taylor LJ, Jackson TL, Reid JG, Duffy SR. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 September; 110(9): 794-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511960&dopt=Abstract
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The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors, progesterone receptors, and Ki-67 antigen. Author(s): Tregon ML, Blumel JE, Tarin JJ, Cano A. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627041&dopt=Abstract
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The effect of catecholamines, acetylcholine and histamine on progesterone release by human granulosa cells in a granulosa cell superfusion system. Author(s): Bodis J, Koppan M, Kornya L, Tinneberg HR, Torok A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 August; 16(4): 259-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396553&dopt=Abstract
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The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram. Author(s): Bokhari S, Bergmann SR. Source: Journal of the American College of Cardiology. 2002 September 18; 40(6): 1092-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354433&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397212&dopt=Abstract
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The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer. Author(s): Lee SH, Chung MA, Quddus MR, Steinhoff MM, Cady B. Source: American Journal of Surgery. 2003 October; 186(4): 348-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14553848&dopt=Abstract
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The effect of progesterone and synthetic progestins on serum- and estradiolstimulated proliferation of human breast cancer cells. Author(s): Seeger H, Wallwiener D, Mueck AO. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2003 February; 35(2): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734785&dopt=Abstract
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The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes. Author(s): Astle S, Khan RN, Thornton S. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 June; 110(6): 589-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798477&dopt=Abstract
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The effects of progesterone on matrix metalloproteinases in cultured human gingival fibroblasts. Author(s): Lapp CA, Lohse JE, Lewis JB, Dickinson DP, Billman M, Hanes PJ, Lapp DF. Source: J Periodontol. 2003 March; 74(3): 277-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710746&dopt=Abstract
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The effects of short-term medroxyprogesterone acetate and micronized progesterone on glucose metabolism and lipid profiles in patients with polycystic ovary syndrome: a prospective randomized study. Author(s): Bagis T, Gokcel A, Zeyneloglu HB, Tarim E, Kilicdag EB, Haydardedeoglu B. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4536-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364431&dopt=Abstract
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The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21. Author(s): Auchus RJ, Sampath Kumar A, Andrew Boswell C, Gupta MK, Bruce K, Rath NP, Covey DF. Source: Archives of Biochemistry and Biophysics. 2003 January 1; 409(1): 134-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464252&dopt=Abstract
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The human kidney is a progesterone-metabolizing and androgen-producing organ. Author(s): Quinkler M, Bumke-Vogt C, Meyer B, Bahr V, Oelkers W, Diederich S. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2803-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788891&dopt=Abstract
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The impact of estrogen and progesterone on asthma. Author(s): Haggerty CL, Ness RB, Kelsey S, Waterer GW. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 March; 90(3): 284-91; Quiz 291-3, 347. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669890&dopt=Abstract
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The impact of progesterone receptor expression on relapse in the long-term clinical course of 93 benign meningiomas. Author(s): Strik HM, Strobelt I, Pietsch-Breitfeld B, Iglesias-Rozas JR, Will B, Meyermann R. Source: In Vivo. 2002 July-August; 16(4): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224136&dopt=Abstract
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The induction of baboon glycodelin expression by progesterone is not through Sp1. Author(s): Jaffe RC, Donnelly KM, Fazleabas AT. Source: Molecular Human Reproduction. 2003 January; 9(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529418&dopt=Abstract
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The inhibitory function in human progesterone receptor N termini binds SUMO-1 protein to regulate autoinhibition and transrepression. Author(s): Abdel-Hafiz H, Takimoto GS, Tung L, Horwitz KB. Source: The Journal of Biological Chemistry. 2002 September 13; 277(37): 33950-6. Epub 2002 July 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114521&dopt=Abstract
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The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy. Author(s): Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O. Source: Human Reproduction (Oxford, England). 2002 September; 17(9): 2315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202418&dopt=Abstract
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The oestrogen-progesterone receptor ratio: an indicator of breast cancer evolution. Author(s): Cherubini M, Baxa P, Guarino G. Source: Chir Ital. 2002 July-August; 54(4): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239750&dopt=Abstract
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The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors. Author(s): Lindgren PR, Backstrom T, Cajander S, Damber MG, Mahlck CG, Zhu D, Olofsson JI. Source: International Journal of Oncology. 2002 September; 21(3): 583-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168103&dopt=Abstract
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The potential of preoperative beta-hCG and progesterone levels to predict failure of laparoscopic linear salpingostomy in ectopic pregnancies. Author(s): Tews G, Ebner T, Yaman C, Polz W, Sommergruber M, Hartl J. Source: The Journal of the American Association of Gynecologic Laparoscopists. 2002 November; 9(4): 460-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386356&dopt=Abstract
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The production of progesterone and 5,6-epoxyeicosatrienoic acid by human granulosa cells. Author(s): Zosmer A, Elder MG, Sullivan MH. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 August; 81(45): 369-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361727&dopt=Abstract
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The role of mitogen-activated protein kinase in insulin and insulin-like growth factor I (IGF-I) signaling cascades for progesterone and IGF-binding protein-1 production in human granulosa cells. Author(s): Seto-Young D, Zajac J, Liu HC, Rosenwaks Z, Poretsky L. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843192&dopt=Abstract
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The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis. Author(s): Anderson E. Source: Breast Cancer Research : Bcr. 2002; 4(5): 197-201. Epub 2002 July 24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223124&dopt=Abstract
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Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Author(s): Leonetti HB, Wilson KJ, Anasti JN. Source: Fertility and Sterility. 2003 January; 79(1): 221-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524095&dopt=Abstract
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Topical progesterone. Author(s): Lee JR. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 374-7; Author Reply 3779. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851524&dopt=Abstract
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Topical progesterone. Author(s): Burry KA. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 373-4; Author Reply 3779. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851523&dopt=Abstract
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Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women. Author(s): Wren BG, Champion SM, Willetts K, Manga RZ, Eden JA. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544672&dopt=Abstract
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Twice-weekly transdermal estradiol and vaginal progesterone as continuous combined hormone replacement therapy in postmenopausal women: a 1-year prospective study. Author(s): Cicinelli E, de Ziegler D, Galantino P, Pinto V, Barba B, Morgese S, Schonauer S. Source: American Journal of Obstetrics and Gynecology. 2002 September; 187(3): 556-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237627&dopt=Abstract
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Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells. Author(s): Ballare C, Uhrig M, Bechtold T, Sancho E, Di Domenico M, Migliaccio A, Auricchio F, Beato M. Source: Molecular and Cellular Biology. 2003 March; 23(6): 1994-2008. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612073&dopt=Abstract
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Unfolding the action of progesterone receptors. Author(s): Li X, O'Malley BW. Source: The Journal of Biological Chemistry. 2003 October 10; 278(41): 39261-4. Epub 2003 July 31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893816&dopt=Abstract
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Up-regulation and nuclear localization of beta-catenin in endometrial carcinoma in response to progesterone therapy. Author(s): Saegusa M, Hamano M, Kuwata T, Yoshida T, Hashimura M, Akino F, Watanabe J, Kuramoto H, Okayasu I. Source: Cancer Science. 2003 January; 94(1): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708483&dopt=Abstract
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Vaginal micronized progesterone in continuous hormone replacement therapy. A prospective randomized study. Author(s): Ferrero S, Gerbaldo D, Fulcheri E, Cristoforoni P. Source: Minerva Ginecol. 2002 December; 54(6): 519-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432337&dopt=Abstract
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Vaginal rings delivering progesterone and estradiol may be a new method of hormone replacement therapy. Author(s): Maruo T, Mishell DR, Ben-Chetrit A, Hochner-Celnikier D, Hamada AL, Nash HA. Source: Fertility and Sterility. 2002 November; 78(5): 1010-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413986&dopt=Abstract
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WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation. Author(s): Banerjee S, Saxena N, Sengupta K, Tawfik O, Mayo MS, Banerjee SK. Source: Neoplasia (New York, N.Y.). 2003 January-February; 5(1): 63-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659671&dopt=Abstract
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Zona pellucida-induced acrosome reaction in human sperm: dependency on activation of pertussis toxin-sensitive G(i) protein and extracellular calcium, and priming effect of progesterone and follicular fluid. Author(s): Schuffner AA, Bastiaan HS, Duran HE, Lin ZY, Morshedi M, Franken DR, Oehninger S. Source: Molecular Human Reproduction. 2002 August; 8(8): 722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149403&dopt=Abstract
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CHAPTER 2. NUTRITION AND PROGESTERONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and progesterone.
Finding Nutrition Studies on Progesterone 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 “progesterone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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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 is a typical result when searching for recently indexed consumer information on progesterone: •
By the way, doctor. I noticed that you listed Crinone, a vaginal progesterone, in one of your articles on products for hormone replacement therapy. Does it really offer as much protection against endometrial cancer as oral progestogens do? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 December; 7(4): 8 1070910X
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Can estrogen be taken without progesterone? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 2000 October; 12(8): 8 1042-1882
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I have recently started taking Prempro (0.625 mg conjugated estrogens/2.5 mg medroxyprogesterone acetate). There is so much written about the benefits of taking estrogen, but I am wondering about the effects of the progesterone component. Will it counteract the benefits of estrogen? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 January; 6(5): 8 1070910X
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I recently had a hysterectomy in which my cervix was not removed. What is the correct hormone replacement therapy for me? Do I have to take progesterone? Will the estrogen increase my risk of cervical cancer? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1998 September; 6(1): 8 1070910X
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Natural progesterone. Author(s): Reproductive Endocrinology and Fertility Division, University of Cincinnati, USA. Source: Liu, J Health-News. 1998 March 31; 4(4): 3 1081-5880
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Progesterone. Source: Anonymous Harv-Womens-Health-Watch. 1999 July; 6(11): 2-3 1070-910X
The following information is typical of that found when using the “Full IBIDS Database” to search for “progesterone” (or a synonym): •
Ultrasonic morphology of the corpora lutea and central luteal cavities during selection of recipients for embryo transfer. Source: Garcia, A. Salaheddine, M. Reproduction-in-Domestic-Animals (Germany). (2000). volume 35(3-4) page 113-118.
Additional physician-oriented references include: •
15-Ketodihydro-PGF(2 alpha), progesterone and uterine involution in primiparous cows with induced retained placenta and post-partal endometritis treated with oxytetracycline and flunixin. Author(s): Department of Obstetrics and Gynaecology, Centre for Reproductive Biology in Uppsala, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
[email protected] Source: Konigsson, K Gustafsson, H Kindahl, H Reprod-Domest-Anim. 2002 February; 37(1): 43-51 0936-6768
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15-ketodihydro-PGF2 alpha, progesterone and cortisol profiles in heifers after induction of parturition by injection of dexamethasone. Author(s): Department of Obstetrics and Gynaecology, Centre for Reproductive Biology in Uppsala, Swedish University of Agricultural Sciences, Uppsala, Sweden.
[email protected] Source: Konigsson, K Kask, K Gustafsson, H Kindahl, H Parvizi, N Acta-Vet-Scand. 2001; 42(1): 151-9 0044-605X
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17beta-estradiol, progesterone and testosterone concentrations in cystic fluids and response to GnRH treatment after emptying of ovarian cysts in dairy cows. Author(s): Institute of Obstetrics and Veterinary Gynaecology, University of Milan, Italy. Source: Cairoli, F Vigo, D Battocchio, M Faustini, M Veronesi, M C Maffeo, G ReprodDomest-Anim. 2002 October; 37(5): 294-8 0936-6768
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Alfa 1 adrenergic potentiation of progesterone accumulation stimulated by vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in cultured rat granulosa cells. Author(s): Department of Clinical Neuroendocrinology Medical Centre of Postgraduate Education, 04-158 Warsaw, Poland.
[email protected] Source: Wasilewska Dziubinska, E Borowiec, M Chmielowska, M Wolinska Witort, E Baranowska, B Neuroendocrinol-Lett. 2002 April; 23(2): 141-8 0172-780X
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Alterations in ovarian follicular progesterone secretion by elevated exposures to the drinking water disinfection by-product dibromoacetic acid: examination of the potential site(s) of impact along the steroidogenic pathway. Author(s): Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
[email protected] Source: Goldman, Jerome M Murr, Ashley S Toxicology. 2002 February 28; 171(2-3): 8393 0300-483X
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Angiotensin converting enzyme in bovine ovarian follicular fluid and its relationship with oestradiol and progesterone. Author(s): Institute of Anatomy and Physiology, the Royal Veterinary and Agricultural University, Frederiksberg C, Denmark.
[email protected] Source: Nielsen, A H Schauser, K H Svenstrup, B Poulsen, K Reprod-Domest-Anim. 2002 April; 37(2): 81-5 0936-6768
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Bisphenol A increases progesterone receptor immunoreactivity in the hypothalamus in a dose-dependent manner and affects sexual behaviour in adult ovariectomized rats. Author(s): Department of Physiology, Yokohama City University School of Medicine, Yokohama, Japan.
[email protected] Source: Funabashi, T Sano, A Mitsushima, D Kimura, F J-Neuroendocrinol. 2003 February; 15(2): 134-40 0953-8194
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Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women. Author(s): School of Medicine, University of California, San Francisco, California 94143, USA. Source: Cummings, J A Brizendine, L Menopause. 2002 Jul-August; 9(4): 253-63 10723714
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Demonstration of mixed properties of RU486 in progesterone receptor (PR)transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues. Author(s): Department of Clinical Research, Singapore General Hospital, Republic of Singapore 169608. Source: Lin, V C Aw, S E Ng, E H Ng, E H Tan, M G Br-J-Cancer. 2001 December 14; 85(12): 1978-86 0007-0920
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Dexamethasone enhances follicle stimulating hormone-induced P450scc mRNA expression and progesterone production in pig granulosa cells. Author(s): Department of Medical Research, Chang-Hua Christian Hospital, Taiwan, ROC. Source: Yang, J G Yu, C C Li, P S Chin-J-Physiol. 2001 September 30; 44(3): 111-9 03044920
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Effect of estrogen and progesterone on the expression of 1, 25-dihydroxyvitamin D receptors mRNA in the liver of ovariectomized rats. Author(s): Department of Endocrionology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. Source: Zhou, Y Ye, R Q Cai, D H Zhang, H Di-Yi-Jun-Yi-Da-Xue-Xue-Bao. 2002 Jun; 22(6): 521-3 1000-2588
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Effect of oestrous synchronization with estradiol 17beta and progesterone on follicular wave dynamics in dairy heifers. Author(s): Pharming B.V., Polsbroek, The Netherlands. Source: Garcia, A Salaheddine, M Reprod-Domest-Anim. 2001 December; 36(6): 301-7 0936-6768
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Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women. Author(s): Sydney Menopause Centre, Royal Hospital for Women, Barker Street, Randwick, New South Wales 2031, Australia. Source: Wren, B G McFarland, K Edwards, L O'Shea, P Sufi, S Gross, B Eden, J A Climacteric. 2000 September; 3(3): 155-60 1369-7137
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Effects of ketoconazole on progesterone and cAMP production in MA-10 mouse Leydig tumor cells. Author(s): Department of Veterinary Medicine, College of Veterinary Medicine, National Chang Hsing University, Taichung, Taiwan, ROC.
[email protected] Source: Chang, C L Fung, H P Biol-Pharm-Bull. 2002 June; 25(6): 794-7 0918-6158
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Estradiol/progesterone substitution in the luteal phase improves pregnancy rates in stimulated cycles--but only in younger women. Author(s): The Center for Human Reproduction and the Foundation for Reproductive Medicine, Chicago, Illinois 60610, USA. Source: Gleicher, N Brown, T Dudkiewicz, A Karande, V Rao, R Balin, M Campbell, D Pratt, D Early-Pregnancy. 2000 January; 4(1): 64-73 1537-6583
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High levels of cholesteryl esters, progesterone and estradiol in the testis of aging male Fischer 344 rats: feminizing Leydig cell tumors. Author(s): School of Health Sciences, Kyorin University, Tokyo, Japan. Source: Konishi, H Okajima, H Okada, Y Yamamoto, H Fukai, K Watanabe, H ChemPharm-Bull-(Tokyo). 1991 February; 39(2): 501-4 0009-2363
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Inhibitors of receptor tyrosine kinases do not suppress progesterone-induced [Ca2+]i signalling in human spermatozoa. Author(s): School of Biosciences, University of Birmingham, B15 2TT, UK.
[email protected] Source: Kirkman Brown, J C Lefievre, L Bray, C Stewart, P M Barratt, C L R Publicover, S J Mol-Hum-Reprod. 2002 April; 8(4): 326-32 1360-9947
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Interaction of prostaglandin F(2alpha) and prostaglandin E(2) on progesterone production in human granulosa-luteal cells. Author(s): Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, B.C., Canada. Source: Vaananen, J E Tong, B L Vaananen, C C Chan, I H Yuen, B H Leung, P C BiolSignals-Recept. 2001 Nov-December; 10(6): 380-8 1422-4933
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Micronized progesterone regulation of the endometrial glandular cycling pool. Author(s): LAC, USC Medical Center, Los Angeles, CA, USA. Source: Moyer, D L Felix, J C Kurman, R J Cuffie, C A Int-J-Gynecol-Pathol. 2001 October; 20(4): 374-9 0277-1691
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Natural vaginal progesterone is associated with minimal psychological side effects: a preliminary study. Author(s): Department of Obstetrics and Gynecology, Columbia College of Physicians and Surgeons, New York, New York, USA. Source: Shantha, S Brooks Gunn, J Locke, R J Warren, M P J-Womens-Health-GendBased-Med. 2001 December; 10(10): 991-7 1524-6094
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Nongenomic action of progesterone in rat aorta: role of nitric oxide and prostaglandins. Author(s): Catedra de Analisis Clinicos II, Departamento de Biologia, Bioquimica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN, Bahia Blanca, Argentina. Source: Selles, Juana Polini, Nelida Alvarez, Cristina Massheimer, Virginia Cell-Signal. 2002 May; 14(5): 431-6 0898-6568
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Progesterone and estradiol enhance lipid mediated transfection of Sk-Br-3 mammalian cancer cells. Author(s): Department of Obstetrics and Gynecology, Medical University of Lubeck, Ratzeburger Allee 160, Germany.
[email protected] Source: Koster, Frank Felberbaum, Ricardo Finas, Dominique Wunsch, Kurt Schulz, Christiane Diedrich, Klaus Hauser, Charlotte Int-J-Mol-Med. 2002 June; 9(6): 617-20 1107-3756
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Progesterone induced modulations of serum hormonal profiles in adult male and female rats. Author(s): Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, 27599, USA.
[email protected] Source: Jeyaraj, D A Mani Maran, R R Aruldhas, M M Govindarajulu, P Endocr-Res. 2001 Feb-May; 27(1-2): 223-32 0743-5800
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Regulation of cyclooxygenase activity and progesterone production in the rat corpus luteum by inducible nitric oxide synthase. Author(s): Department of Obstetrics and Gynecology, Hadassah University Hospital, Mt Scopus, Jerusalem, IL-91240, Israel.
[email protected] Source: Hurwitz, A Finci Yeheskel, Z Milwidsky, A Mayer, M Reproduction. 2002 May; 123(5): 663-9 1470-1626
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Relationship between ultrasonographic assessment of the corpus luteum and plasma progesterone concentrations during the oestrus cycle in monovular ewes. Source: Bulnes, A. Gonzalez de Santiago Moreno, J. Gomez Brunet, A. Lopez Sebastian, A. Reproduction-in-Domestic-Animals (Germany). (2000). volume 35(2) page 65-68. sheep corpus luteum ultrasonics diagnosis progesterone 0936-6768
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Schistosomiasis (mansoni) has a negative impact on serum levels of estradiol, progesterone and prolactin in the female baboon (Papio cynocephalus anubis). Author(s): SLU, Uppsala (Sweden) Source: Farah, I.O. Andersson, E. Mwenda, J. Wango, E. Hau, J. Scandinavian-Journalof-Laboratory-Animal-Science (Denmark). (2001). volume 28(4) page 193-199. monkeys schistosoma mansoni oestrogens progesterone prolactin laboratory animals 0901-3393
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Steroid hormone progesterone induces cell proliferation and abnormal mitotic processes in rat liver. Author(s): Department of Clinical Sciences, Health Sciences Center and Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Spain.
[email protected] Source: Boada, Luis D Zumbado, Manuel del, Rio Isidoro Blanco, Alfonso Torres, Santiago Monterde, Jose G Afonso, Juan L Cabrera, Juan J Diaz Chico, Bonifacio N ArchToxicol. 2002 January; 75(11-12): 707-16 0340-5761
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The effect of timing of administration of oestradiol benzoate on characteristics of oestrus, timing of ovulation and fertility in Bos indicus heifers synchronised with a progesterone releasing intravaginal insert. Author(s): Department of Veterinary Science, University of Melbourne, Werribee, Victoria. Source: Cavalieri, J Coleman, C Rodrigues, H Macmillan, K L Fitzpatrick, L A Aust-VetJ. 2002 April; 80(4): 217-23 0005-0423
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The lipoxygenase pathways are involved in LH-stimulated progesterone production in bovine corpus luteum. Author(s): Department of Animal Science, Faculty of Agriculture, Okayama University, Japan. Source: Taniguchi, Hiroaki Uenoyama, Yoshihisa Miyamoto, Yoko Okuda, Kiyoshi Prostaglandins-Other-Lipid-Mediat. 2002 January; 67(1): 49-60 1098-8823
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The roles of estrogen and progesterone in regulating carbohydrate and fat utilization at rest and during exercise. Author(s): Department of Exercise Science, University of Massachusetts, Amherst 01003, USA. Source: D'Eon, Tara Braun, Barry J-Womens-Health-Gend-Based-Med. 2002 April; 11(3): 225-37 1524-6094
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Zona pellucida-induced acrosome reaction in human sperm: dependency on activation of pertussis toxin-sensitive G(i) protein and extracellular calcium, and priming effect of progesterone and follicular fluid. Author(s): The Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, USA. Source: Schuffner, A A Bastiaan, H S Duran, H E Lin, Z Y Morshedi, M Franken, D R Oehninger, S Mol-Hum-Reprod. 2002 August; 8(8): 722-7 1360-9947
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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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to progesterone; 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: •
Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Zinc Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. PROGESTERONE
ALTERNATIVE
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to progesterone. 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 progesterone 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 “progesterone” (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 progesterone: •
(-)-Epigallocatechin gallate inhibits mos activation-mediated xenopus oocyte maturation induced by progesterone. Author(s): Yasokawa M, Sugimoto I, Fukuma M, Goto N, Kobayashi N, Yasuda H, Ogura K, Iwashita J, Nagata K, Hiji Y, Hashimoto E. Source: Febs Letters. 1999 December 17; 463(3): 317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10606745&dopt=Abstract
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17Beta-estradiol and progesterone supplementation in extremely low-birth-weight infants. Author(s): Trotter A, Maier L, Grill HJ, Wudy SA, Pohlandt F. Source: Pediatric Research. 1999 April; 45(4 Pt 1): 489-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203139&dopt=Abstract
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17Beta-estradiol, its metabolites, and progesterone inhibit cardiac fibroblast growth. Author(s): Dubey RK, Gillespie DG, Jackson EK, Keller PJ. Source: Hypertension. 1998 January; 31(1 Pt 2): 522-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9453356&dopt=Abstract
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A 2-year prospective study on the effects of depot medroxyprogesterone acetate on bone mass-response to estrogen and calcium therapy in individual users. Author(s): Merki-Feld GS, Neff M, Keller PJ. Source: Contraception. 2003 February; 67(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586317&dopt=Abstract
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A phase II trial of mitomycin C, 5'-deoxy-5-fluorouridine, etoposide and medroxyprogesterone acetate (McVD-MPA) as a salvage chemotherapy to anthracycline-resistant tumor in relapsed breast cancer and its mechanism(s) of antitumor action. Author(s): Kim R, Osaki A, Tanabe K, Kojima J, Toge T. Source: Oncol Rep. 2001 May-June; 8(3): 597-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295087&dopt=Abstract
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A phase II/pharmacokinetic trial of high-dose progesterone in combination with paclitaxel. Author(s): Aebi S, Schnider TW, Los G, Heath DD, Darrah D, Kirmani S, McClay EF, D'Agostino H, Plaxe SC, Fink D, De las Alas MM, Howell SB, Christen RD. Source: Cancer Chemotherapy and Pharmacology. 1999; 44(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453729&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724519&dopt=Abstract
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Antiproliferative effects of low-dose micronized progesterone. Author(s): Kim S, Korhonen M, Wilborn W, Foldesy R, Snipes W, Hodgen GD, Anderson FD. Source: Fertility and Sterility. 1996 February; 65(2): 323-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8566256&dopt=Abstract
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Binding of p23 and hsp90 during assembly with the progesterone receptor. Author(s): Johnson JL, Toft DO. Source: Molecular Endocrinology (Baltimore, Md.). 1995 June; 9(6): 670-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8592513&dopt=Abstract
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Brain androgen and progesterone metabolizing enzymes: biosynthesis, distribution and function. Author(s): Lephart ED, Lund TD, Horvath TL. Source: Brain Research. Brain Research Reviews. 2001 November; 37(1-3): 25-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744072&dopt=Abstract
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C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. Author(s): Leonessa F, Kim JH, Ghiorghis A, Kulawiec RJ, Hammer C, Talebian A, Clarke R. Source: Journal of Medicinal Chemistry. 2002 January 17; 45(2): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784143&dopt=Abstract
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Changes of circulating leptin levels during normal menstrual cycle: relationship to estradiol and progesterone. Author(s): Lin KC. Source: Kaohsiung J Med Sci. 1999 October; 15(10): 597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603707&dopt=Abstract
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Cisplatin, adriamycin, etoposide, megestrol acetate versus melphalan, 5-fluorouracil, medroxyprogesterone acetate in the treatment of endometrial carcinoma. Author(s): Cornelison TL, Baker TR, Piver MS, Driscoll DL. Source: Gynecologic Oncology. 1995 November; 59(2): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7590480&dopt=Abstract
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Clearing up confusion over yams and progesterone. Author(s): Dentali S. Source: Alternative Therapies in Health and Medicine. 1996 July; 2(4): 19-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8795909&dopt=Abstract
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Combined effect of navelbine with medroxyprogesterone acetate against human breast carcinoma MCF-7 cells in vitro. Author(s): Sugiyama K, Shimizu M, Akiyama T, Ishida H, Okabe M, Tamaoki T, Akinaga S. Source: British Journal of Cancer. 1998 June; 77(11): 1737-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9667641&dopt=Abstract
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Differing effects of endocrine-disrupting chemicals on basal and FSH-stimulated progesterone production in rat granulosa-luteal cells. Author(s): Nejaty H, Lacey M, Whitehead SA. Source: Experimental Biology and Medicine (Maywood, N.J.). 2001 June; 226(6): 570-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11395928&dopt=Abstract
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Diverse effects of tyrosine kinase inhibitors on follicle-stimulating hormonestimulated estradiol and progesterone production from rat granulosa cells in serumcontaining medium and serum-free medium containing epidermal growth factor. Author(s): Haynes-Johnson D, Lai MT, Campen C, Palmer S. Source: Biology of Reproduction. 1999 July; 61(1): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10377043&dopt=Abstract
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Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats. Author(s): Panossian A, Kochikian A, Gabrielian E, Muradian R, Stepanian H, Arsenian F, Wagner H. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 1999 July; 6(3): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439479&dopt=Abstract
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Effect of anticoagulants and sampling time on results of progesterone determination in canine blood samples. Author(s): Thuroczy J, Wolfling A, Tibold A, Balogh L, Janoki GA, Solti L. Source: Reproduction in Domestic Animals = Zuchthygiene. 2003 October; 38(5): 386-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950690&dopt=Abstract
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Effect of dietary selenium supplementation on the plasma progesterone concentration in cows. Author(s): Kamada H, Hodate K. Source: The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science. 1998 January; 60(1): 133-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9492375&dopt=Abstract
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Effect of estrogen agonists and antagonists on induction of progesterone receptor in a rat hypothalamic cell line. Author(s): Fitzpatrick SL, Berrodin TJ, Jenkins SF, Sindoni DM, Deecher DC, Frail DE. Source: Endocrinology. 1999 September; 140(9): 3928-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465261&dopt=Abstract
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Effect of genistein, tyrphostin and herbimycin on prolactin-stimulated progesterone production by porcine theca and luteal cells. Author(s): Gregoraszczuk E, Slomczynska M, Stoklosowa S. Source: Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society. 1999 September; 50(3): 477-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10574476&dopt=Abstract
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Effect of intraovarian factors on porcine follicular cells: cumulus expansion, granulosa and cumulus cell progesterone production. Author(s): Jezova M, Scsukova S, Nagyova E, Vranova J, Prochazka R, Kolena J.
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Source: Animal Reproduction Science. 2001 January 31; 65(1-2): 115-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182513&dopt=Abstract •
Effect of large dietary doses of beta-carotene on plasma retinoid and beta-carotene levels and on progesterone production in the granulosa cells of Japanese quail. Author(s): Pusztai A, Agota G, Bardos L. Source: Acta Vet Hung. 2000; 48(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11402678&dopt=Abstract
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Effect of luteinizing hormone (LH), PGE2, 8-EPI-PGE1, 8-EPI-PGE2, trichosanthin, and pregnancy specific protein B (PSPB) on secretion of progesterone in vitro by corpora lutea (CL) from nonpregnant and pregnant cows. Author(s): Weems YS, Lammoglia MA, Vera-Avila HR, Randel RD, King C, Sasser RG, Weems CW. Source: Prostaglandins & Other Lipid Mediators. 1998 January; 55(1): 27-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9661216&dopt=Abstract
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Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells. Author(s): Panno ML, Salerno M, Pezzi V, Sisci D, Maggiolini M, Mauro L, Morrone EG, Ando S. Source: Journal of Cancer Research and Clinical Oncology. 1996; 122(12): 745-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8954172&dopt=Abstract
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Effect of peripheral concentrations of progesterone on follicular growth and fertility in ewes. Author(s): Johnson SK, Dailey RA, Inskeep EK, Lewis PE. Source: Domestic Animal Endocrinology. 1996 January; 13(1): 69-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8625617&dopt=Abstract
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Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect. Author(s): Henmi H, Endo T, Kitajima Y, Manase K, Hata H, Kudo R. Source: Fertility and Sterility. 2003 August; 80(2): 459-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909517&dopt=Abstract
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Effects of demethylzeylasteral and celastrol on spermatogenic cell Ca2+ channels and progesterone-induced sperm acrosome reaction. Author(s): Bai JP, Shi YL, Fang X, Shi QX. Source: European Journal of Pharmacology. 2003 March 7; 464(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600689&dopt=Abstract
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Effects of dietary fat on follicular development and circulating concentrations of lipids, insulin, progesterone, estradiol-17 beta, 13,14-dihydro-15-keto-prostaglandin F(2 alpha), and growth hormone in estrous cyclic Brahman cows. Author(s): Lammoglia MA, Willard ST, Hallford DM, Randel RD. Source: Journal of Animal Science. 1997 June; 75(6): 1591-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9250522&dopt=Abstract
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Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: a PET study. Author(s): Moses EL, Drevets WC, Smith G, Mathis CA, Kalro BN, Butters MA, Leondires MP, Greer PJ, Lopresti B, Loucks TL, Berga SL. Source: Biological Psychiatry. 2000 October 15; 48(8): 854-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063980&dopt=Abstract
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Effects of estrogen and progesterone on urinary bladder in female rabbit: evaluation by quantitative morphometric analysis. Author(s): Hashimoto T, Ishigooka M, Zermann DH, Sasagawa I, Nakada T. Source: Urology. 1999 March; 53(3): 642-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10096402&dopt=Abstract
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Effects of Lepidium meyenii Walp and Jatropha macrantha on blood levels of estradiol-17 beta, progesterone, testosterone and the rate of embryo implantation in mice. Author(s): Oshima M, Gu Y, Tsukada S. Source: The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science. 2003 October; 65(10): 1145-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14600359&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774816&dopt=Abstract
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Evaluation of the ICAGEN-Target canine ovulation timing diagnostic test in detecting canine plasma progesterone concentrations. Author(s): Manothaiudom K, Johnston SD, Hegstad RL, Hardy SK. Source: Journal of the American Animal Hospital Association. 1995 January-February; 31(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7820766&dopt=Abstract
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Expression pattern and role of a 60-kilodalton progesterone binding protein in regulating granulosa cell apoptosis: involvement of the mitogen-activated protein
Alternative Medicine 131
kinase cascade. Author(s): Peluso JJ, Bremner T, Fernandez G, Pappalardo A, White BA. Source: Biology of Reproduction. 2003 January; 68(1): 122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493703&dopt=Abstract •
Ginseng flowers stimulate progesterone production from bovine luteal cells. Author(s): Wu LS, Sheu SY, Huang CC, Chiu CH, Huang JC, Yang JR, Lian WX, Lai CH, Chen YP, Lin JH. Source: The American Journal of Chinese Medicine. 2000; 28(3-4): 371-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154050&dopt=Abstract
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Herbal treatments for menopause. Black cohosh, soy and micronized progesterone. Author(s): Pick M. Source: Adv Nurse Pract. 2000 May; 8(5): 29-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235332&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529413&dopt=Abstract
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Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein. Author(s): Ushigome F, Takanaga H, Matsuo H, Yanai S, Tsukimori K, Nakano H, Uchiumi T, Nakamura T, Kuwano M, Ohtani H, Sawada Y. Source: European Journal of Pharmacology. 2000 November 10; 408(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11070177&dopt=Abstract
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Inhibitors of receptor tyrosine kinases do not suppress progesterone-induced [Ca2+]i signalling in human spermatozoa. Author(s): Kirkman-Brown JC, Lefievre L, Bray C, Stewart PM, Barratt CL, Publicover SJ. Source: Molecular Human Reproduction. 2002 April; 8(4): 326-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912280&dopt=Abstract
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Inhibitory effect of free radicals derived from organic hydroperoxide on progesterone synthesis in human term placental mitochondria. Author(s): Klimek J, Wozniak M, Szymanska G, Zelewski L.
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Source: Free Radical Biology & Medicine. 1998 May; 24(7-8): 1168-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9626571&dopt=Abstract •
Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma. Author(s): Kriegmair M, Oberneder R, Hofstetter A. Source: Urology. 1995 May; 45(5): 758-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7747370&dopt=Abstract
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Intracellular regulation of estradiol and progesterone production by cultured bovine granulosa cells. Author(s): Legault S, Bailey JL, Fortier MA, Rouillier P, Guilbault LA. Source: Molecular Reproduction and Development. 1999 December; 54(4): 371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10542377&dopt=Abstract
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Intravascular infusion of lipid into ewes stimulates production of progesterone and prostaglandin. Author(s): Burke JM, Carroll DJ, Rowe KE, Thatcher WW, Stormshak F. Source: Biology of Reproduction. 1996 July; 55(1): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8793072&dopt=Abstract
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Isocupressic acid blocks progesterone production from bovine luteal cells. Author(s): Wu LS, Chen JC, Sheu SY, Huang CC, Kuo YH, Chiu CH, Lian WX, Yang CJ, Kaphle K, Lin JH. Source: The American Journal of Chinese Medicine. 2002; 30(4): 533-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568280&dopt=Abstract
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Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side effects of gonadotropin-releasing hormone agonist without changing its efficacy in endometriosis. Author(s): Makarainen L, Ronnberg L, Kauppila A. Source: Fertility and Sterility. 1996 January; 65(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8557151&dopt=Abstract
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Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep. Author(s): Saaresranta T, Polo-Kantola P, Rauhala E, Polo O. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2001 December; 18(6): 989-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829107&dopt=Abstract
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Metabolism of a [18F]fluorine labeled progestin (21-[18F]fluoro-16 alpha-ethyl-19norprogesterone) in humans: a clue for future investigations.
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Author(s): Verhagen A, Studeny M, Luurtsema G, Visser GM, De Goeij CC, Sluyser M, Nieweg OE, Van der Ploeg E, Go KG, Vaalburg W. Source: Nuclear Medicine and Biology. 1994 October; 21(7): 941-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9234348&dopt=Abstract •
Mitomycin C, methotrexate, and vincristine with medroxyprogesterone acetate or prednisolone for doxorubicin resistant advanced breast cancer--a randomized control study. Author(s): Tashiro H, Nomura Y. Source: Anticancer Res. 1995 September-October; 15(5B): 2229-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8572630&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704030&dopt=Abstract
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Natural progesterone. Author(s): Liu J. Source: Health News. 1998 March 31; 4(4): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9553604&dopt=Abstract
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Progesterone accelerates the onset of capacitation in mouse sperm via T-type calcium channels. Author(s): Senuma M, Yamano S, Nakagawa K, Irahara M, Kamada M, Aono T. Source: Archives of Andrology. 2001 April-June; 47(2): 127-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11554684&dopt=Abstract
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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636333&dopt=Abstract
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Progesterone potentiating effect of Dipsacus mitis D. Don for its contraceptive action in hamster. Author(s): Kitchlu S, Mehrotra PK, Singh S. Source: Indian J Exp Biol. 1999 April; 37(4): 402-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641178&dopt=Abstract
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Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa. Author(s): Luconi M, Krausz C, Barni T, Vannelli GB, Forti G, Baldi E. Source: Molecular Human Reproduction. 1998 March; 4(3): 251-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9570271&dopt=Abstract
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Proliferative effects of combination estrogen and progesterone replacement therapy on the normal postmenopausal mammary gland in a murine model. Author(s): Raafat AM, Hofseth LJ, Haslam SZ. Source: American Journal of Obstetrics and Gynecology. 2001 February; 184(3): 340-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228484&dopt=Abstract
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Protein tyrosine kinase activity of lavendustin A and the phytoestrogen genistein on progesterone synthesis in cultured rat ovarian cells. Author(s): Whitehead SA, Lacey M. Source: Fertility and Sterility. 2000 March; 73(3): 613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689022&dopt=Abstract
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Purification, characterization and partial peptide microsequencing of progesterone 5 beta-reductase from shoot cultures of Digitalis purpurea. Author(s): Gartner DE, Keilholz W, Seitz HU. Source: European Journal of Biochemistry / Febs. 1994 November 1; 225(3): 1125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7957203&dopt=Abstract
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Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Author(s): Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G. Source: Analytical and Bioanalytical Chemistry. 2003 October 25 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14579009&dopt=Abstract
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Relationships of peri-partum, plasma concentrations of progesterone, oestrogens and 13,14-dihydro-15-ketoprostaglandin F2alpha in heifers and of anatomical measurements of dam and calf with difficulty of calving in early-bred Hereford x Friesian heifers. Author(s): Olujohungbe AA, Bryant MJ, Cobby JM, Pope GS. Source: Animal Reproduction Science. 1998 June 30; 52(1): 1-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9728810&dopt=Abstract
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Sex differences in anxiety, sensorimotor gating and expression of the alpha4 subunit of the GABAA receptor in the amygdala after progesterone withdrawal. Author(s): Gulinello M, Orman R, Smith SS.
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Source: The European Journal of Neuroscience. 2003 February; 17(3): 641-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581182&dopt=Abstract •
Single cell analysis of tyrosine kinase dependent and independent Ca2+ fluxes in progesterone induced acrosome reaction. Author(s): Tesarik J, Carreras A, Mendoza C. Source: Molecular Human Reproduction. 1996 April; 2(4): 225-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9238684&dopt=Abstract
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Stimulation of protein tyrosine phosphorylation by platelet-activating factor and progesterone in human spermatozoa. Author(s): Luconi M, Bonaccorsi L, Krausz C, Gervasi G, Forti G, Baldi E. Source: Molecular and Cellular Endocrinology. 1995 February 27; 108(1-2): 35-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7758838&dopt=Abstract
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Stimulation of tyrosine phosphorylation by progesterone and its 11-OH derivatives: dissection of a Ca(2+)-dependent and a Ca(2+)-independent mechanism. Author(s): Martinez F, Tesarik J, Martin CM, Soler A, Mendoza C. Source: Biochemical and Biophysical Research Communications. 1999 February 5; 255(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082649&dopt=Abstract
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The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Author(s): Recker RR, Davies KM, Dowd RM, Heaney RP. Source: Annals of Internal Medicine. 1999 June 1; 130(11): 897-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10375338&dopt=Abstract
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The effect of microtubule-disrupting drugs on morphology, progesterone and prorenin secretion of bovine cultured ovarian theca cells. Author(s): Brunswig-Spickenheier B, Bilinska B, Stoklosowa S. Source: Acta Histochemica. 1996 November; 98(4): 389-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8960303&dopt=Abstract
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The effects of feeding an Asian or Western diet on sperm numbers, sperm quality and serum hormone levels in cynomolgus monkeys (Macaca fascicularis) injected with testosterone enanthate (TE) plus depot medroxyprogesterone acetate (DMPA). Author(s): Suhana N, Sutyarso, Moeloek N, Soeradi O, Sri Sukmaniah S, Supriatna J. Source: International Journal of Andrology. 1999 April; 22(2): 102-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194642&dopt=Abstract
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The progesterone receptor and ubiquitin are differentially regulated within the endometrial glands of the natural and stimulated cycle. Author(s): Bebington C, Doherty FJ, Ndukwe G, Fleming SD. Source: Molecular Human Reproduction. 2000 March; 6(3): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694275&dopt=Abstract
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The role of mitogen-activated protein kinase in insulin and insulin-like growth factor I (IGF-I) signaling cascades for progesterone and IGF-binding protein-1 production in human granulosa cells. Author(s): Seto-Young D, Zajac J, Liu HC, Rosenwaks Z, Poretsky L. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843192&dopt=Abstract
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Topical progesterone cream application and overdosing. Author(s): Ilyia EF, McLure D, Farhat MY. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 1998 Spring; 4(1): 5-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9553828&dopt=Abstract
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Transvaginal progesterone: evidence for a new functional 'portal system' flowing from the vagina to the uterus. Author(s): Cicinelli E, de Ziegler D. Source: Human Reproduction Update. 1999 July-August; 5(4): 365-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465526&dopt=Abstract
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Tyrosine kinase inhibition reduces the plateau phase of the calcium increase in response to progesterone in human sperm. Author(s): Bonaccorsi L, Luconi M, Forti G, Baldi E. Source: Febs Letters. 1995 May 1; 364(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750549&dopt=Abstract
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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WebMDHealth: 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 progesterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Endometriosis Source: Healthnotes, Inc.; www.healthnotes.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com
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Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com PMS Source: Integrative Medicine Communications; www.drkoop.com PMS Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Premenstrual Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Sleep Apnea Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Androstenedione Source: Healthnotes, Inc.; www.healthnotes.com Angelica Sinensis Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Astragalus SP Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Calciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Chaste Tree Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca
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Chasteberry Source: Prima Communications, Inc.www.personalhealthzone.com Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Chinese Angelica Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Damiana Alternative names: Turnera diffusa Source: Healthnotes, Inc.; www.healthnotes.com Danggui Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Dioscorea Villosa Source: Integrative Medicine Communications; www.drkoop.com Dong Quai Alternative names: Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Estrogen Source: Prima Communications, Inc.www.personalhealthzone.com Estrogens (combined) Source: Healthnotes, Inc.; www.healthnotes.com German Chamomile Alternative names: Matricaria recutita Source: Integrative Medicine Communications; www.drkoop.com
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GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Matricaria Recutita Source: Integrative Medicine Communications; www.drkoop.com Medroxyprogesterone Source: Healthnotes, Inc.; www.healthnotes.com Mifepristone Source: Healthnotes, Inc.; www.healthnotes.com Natural Progesterone Cream Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10099,00.html Oral Contraceptives Source: Prima Communications, Inc.www.personalhealthzone.com Origanum Alternative names: Oregano; Origanum vulgare Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Prempro Source: Healthnotes, Inc.; www.healthnotes.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Source: Integrative Medicine Communications; www.drkoop.com
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Sarsaparilla Alternative names: Smilax spp. Source: Healthnotes, Inc.; www.healthnotes.com Tang Kuei Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com Wild Yam Alternative names: Dioscorea villosa Source: Healthnotes, Inc.; www.healthnotes.com Wild Yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Source: Prima Communications, Inc.www.personalhealthzone.com Wild Yam Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10070,00.html
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON PROGESTERONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to progesterone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “progesterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on progesterone, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Progesterone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to progesterone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
16a-hydroxylation of Progesterone by Rat Liver by Salti, Ibrahim Saba; AdvDeg from University of Toronto (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK09566
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17-beta Estradiol and Progesterone-induced Alterations in Human Type-1/type-2 Cytokine Balance and the Role of Costimulatory and Apoptotic Mechanisms by Maniatis, Eleni; PhD from The Univ. of Texas H.S.C. at Houston Grad. Sch. of Biomed. Sci., 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3046062
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Characterization of Progesterone Receptor in Bovine Corpora Lutea by Bolden-tiller, Olga Untella; PhD from University of Missouri - Columbia, 2002, 198 pages http://wwwlib.umi.com/dissertations/fullcit/3074376
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Differentiation of Bovine Ovarian Follicles during the Periovulatory Period: Receptors for Progesterone and Oxytocin and Effects of Oxytocin on Theca Cells by Jo, Misung; PhD from Cornell University, 2002, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3037319
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Effect of Alpha-melanocyte Stimulating Hormone on Lordosis Role of Estrogen, Progesterone, and Serotonin by Raible, Lyn Helene; PhD from The University of British Columbia (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24195
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Effect of Pregnancy and Role of Progesterone Metabolites in the Regulation of the Activity of Enzymes Bound to the Hepatic Endoplasmic Reticulum by Kardish, Richard; PhD from University of Toronto (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK36710
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Effects of Progesterone Treatment on Sickness Behaviors and the Inflammatory Response to Brain Injury in the Rat by Grossman, Kimberly Joy; PhD from Emory University, 2002, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3072633
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Effects of the Menstrual Cycle on Protein Metabolism during Exercise (ovarian Hormones, Urea Nitrogen Excretion, Progesterone, Sweat, Estradiol) by Lamont, Linda S., PhD from Kent State University, 1984, 161 pages http://wwwlib.umi.com/dissertations/fullcit/8508387
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Enzymeimmunoassay of Progesterone in Milk for Progesterone Profiles and Relationship with Reproductive Performance in Holstein Cows by Christie, Kenneth A; DVSC from University of Guelph (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL44913
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Estrogen and Progesterone Levels in Bovine Milk by Narendran, Rajasingham; PhD from University of Guelph (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31096
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Estrogen and Progesterone Regulation of Uterine Cell Proliferation Differentiation by Chen, Bo; PhD from Yeshiva University, 2003, 224 pages http://wwwlib.umi.com/dissertations/fullcit/3090287
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Estrous Synchronization in Beef Heifers Using Progesterone Intravaginal Insert (cidr), and a Two-injection System of Prostaglandin (lutalyse Rtm), in Conjunction with Two Breeding Regimen by Capt, Emmett Eugene, IV; Ms from Stephen F. Austin State University, 2003, 32 pages http://wwwlib.umi.com/dissertations/fullcit/1413877
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Functional Analyses of the Estrogen and Progesterone Receptors by Thackray, Varykina G.; PhD from University of Colorado Health Sciences Center, 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3056503
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Hormonal Regulation of Myometrial Gap Junctions Control by Estrogen, Progesterone and Prostaglandins by Mackenzie, Leslie Wayne; PhD from Mcmaster University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66171
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Immunocytochemical Localization of Estrogen and Progesterone Receptors in Normal Hyperplastic and Neoplastic Human Endometria by Bergeron, Christine; PhD from Mcgill University (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL57350
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Progesterone and Corticosteroid Interaction during Pregnancy in Ewes by Hua, Yi; PhD from University of Florida, 2002, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3084005
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Progesterone and Estrogens in Intrauterine Tissues during Pregnancy and Labour by Power, Stephen George Alexander; PhD from The University of Western Ontario (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL36082
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Progesterone Metabolism in the Previable Human Fetus by Bird, Charles E; AdvDeg from McGill University (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK01273
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Progesterone Signaling in Ovarian Epithelial Tumors by Zhou, Hong; PhD from University of Southern California, 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3094406
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Retention of Early Pregnancy and Its Relationship to Serum Progesterone in Dairy Cattle by Starbuck, Melanie J.; Ms from West Virginia University, 2002, 64 pages http://wwwlib.umi.com/dissertations/fullcit/1409759
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Steroid Estrogen, Progesterone and Androgen Concentrations in the Plasma of the Domestic Fowl in Relation to the Ovulation Cycle by Peterson, Andrew James; PhD from Mcgill University (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15965
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The Alleviation of Premenstrual Syndrome a Double-blind Placebo-controlled Trial of Progesterone by Maddocks, Sarah E; PhD from Queen's University at Kingston (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL38430
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The Biology of Fatherhood: a Novel Role for Progesterone Receptors in Male Physiology and Behavior by Schneider, Johanna S.; PhD from Northwestern University, 2003, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3087971
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The Effects of Estrogen, Progesterone and Ionized Calcium on Seizures during the Menstrual Cycle of Mature Female Epileptics by Jacono, John; PhD from The University of Western Ontario (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29462
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The Effects of Estrogen, Progesterone, and Testosterone on the Viability and Proliferation of A549 Lung Macrophages in Cell Culture by Hall, Deshannon; Ms from The University of Mississippi Medical Center, 2002, 97 pages http://wwwlib.umi.com/dissertations/fullcit/1408842
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The Effects of Progesterone and Estradiol on the Spontaneous and Gnrh-induced Secretion of Lh and Fsh in the Anestrous and Cyclic Ewe by Rieger, Donald; PhD from The University of Saskatchewan (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK56009
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The in Vivo Conversion Products of Parenterally Administered Progesterone in the Hen by Chen, Percival H; AdvDeg from McGill University (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK03946
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The Role of Progesterone Metabolites and Psychosocial Factors in Mood during Pregnancy and Postpartum: a Biopsychosocial Model by Ross, Lori Elizabeth; PhD from University of Toronto (Canada), 2002, 260 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74735
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND PROGESTERONE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning progesterone.
Recent Trials on Progesterone The following is a list of recent trials dedicated to progesterone.8 Further information on a trial is available at the Web site indicated. •
Comparison of Nolvadex 20 mg and placebo combination to Nolvadex 20 mg and ZD1839 (IRESSA(tm)) 250 mg combination in patients with metastatic breast cancer and estrogen receptor (ER) and/or progesterone (PR) positive tumours Condition(s): Breast Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): AstraZeneca Purpose - Excerpt: This study is being carried out to see if ZD1839 is effective in treating metastatic breast cancer in combination with Nolvadex, and if so, how it compares with Nolvadex alone. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069290
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Progesterone Treatment of Blunt Traumatic Brain Injury Condition(s): Traumatic Brain Injury Study Status: This study is currently recruiting patients. Sponsor(s): Emory University; National Institutes of Health (NIH)
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These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: The purpose of this study is to determine if progesterone treatment safely reduces brain swelling and damage after injury. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048646 •
Progesterone vs Placebo Therapy for Women with Epilepsy Condition(s): Epilepsy Study Status: This study is currently recruiting patients. Sponsor(s): Beth Israel Deaconess Medical Center Purpose - Excerpt: There is considerable evidence to suggest that natural progesterone has anti-seizure properties. The purpose of this study is to determine if progesterone supplement during the second half of the menstrual cycle lessens seizure frequency in women with epilepsy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029536
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Treatment of Uterine Fibroids with CDB-2914, an Progesterone Receptor Antagonist
Experimental Selective
Condition(s): Leiomyoma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This study will evaluate the selective progesterone receptor modulator CDB-2914 for treating uterine fibroids in pre-menopausal women. It will compare fibroid size, hormone levels and symptoms in women who take CDB-2914 with that of women who take a placebo (an inactive substance). The study will also evaluate the endocrine effects of chronic daily administration of CDB-2914, including possible effects on the menstrual cycle and on adrenal gland function. Pre-menopausal women between 33 and 50 years of age who have predictable menstrual cycles of normal length and uterine fibroids of at least 2 cm in size may be eligible for this study. Only women who need and want hysterectomy for treatment of fibroids will be enrolled. Candidates will be screened with a medical history and physical examination, including a breast and pelvic examination, blood and urine tests, and completion of a questionnaire about quality of life. They will be taught to use a kit to test their urine for LH, a hormone produced in large amounts just before ovulation, and will be given a calendar to record the LH surge, as well as any spotting, bleeding, or other symptoms. The study will take place over four menstrual cycles, after which hysterectomy will be performed. Participants will undergo the following procedures: - First (pre-treatment) cycle: Participants will undergo magnetic resonance imaging (MRI) and a special ultrasound test called saline hysterosonogram. MRI uses radio waves and a magnetic field to image body tissues. The subject lies in a narrow metal cylinder (the scanner) for about an hour during the imaging. A contrast material is injected into a vein to brighten the images.
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The saline hysterosonogram involves placing a speculum in the vagina, as if for a Pap test, and then putting a very small amount of liquid inside the uterus, using a small plastic tube. An ultrasound examination is then done by inserting a probe into the vagina. The probe emits and receives sound waves that are used to form a picture of the internal structures. - Second through fourth menstrual cycles - Participants will have a pregnancy test on the first or second day of each cycle. Those who are not pregnant will take CDB-2914 once a day for three menstrual cycles, or up to 102 days if the cycles are irregular. At specific times during the cycles, subject will have blood tests to measure the effect of CDB-2914 on hormones, blood count, blood chemistries, and liver function, and ultrasound tests to check the number and size of follicles in the ovaries. They will test their urine to detect the LH surge and will have additional hormone blood tests. At three times during the study-during the first, second and third menstrual cycles-subjects will bring a 24-hour urine collection to the clinic for measurements of cortisol and adrenal gland function. A transvaginal ultrasound study will be repeated after 4 to 6 weeks of treatment to check fibroid growth. A repeat saline hysterosonogram and MRI will be done within 2 weeks of surgery to count the number of fibroids and measure their size. Women who have completed the study to the end of the four menstrual cycles and still require hysterectomy will stop taking CDB-2914. They will complete another quality of life questionnaire. Their blood levels of CDB-2914 will be measured, and they will have a hysterectomy, in which the uterus, and possibly the ovaries, will be removed. Subjects will be discharged from the hospital 2 to 4 days after surgery and will return to the clinic for post-operative evaluation after 4 to 6 weeks. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044876
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “progesterone” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON PROGESTERONE 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.9 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 “progesterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on progesterone, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Progesterone By performing a patent search focusing on progesterone, 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 9Adapted
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 progesterone: •
Endometriosis mouse model Inventor(s): Boyd; Jeffrey (New York, NY), Strauss; Jerome J. (Wyndmoor, PA), Van Deerlin; Peter (Wynnewood, PA), Yamamoto; Karen K. (San Clemente, CA) Assignee(s): Reprogen, Inc. (Irvine, CA), The Trustees of the Universiy of Pennsylvania (Philadelphia, PA) Patent Number: 6,429,353 Date filed: March 25, 1998 Abstract: The invention provides an endometriosis mouse model wherein severely compromised immune deficient (SCID) female mice are transplanted with human xenografts of normal endometrial tissue, but result in mice with human endometriosis. Typically, the xenografts are treated with a micronized estrogen source prior to transplantation or implantation and the endogenous progesterone of the mice is eliminated also prior to transplantation of the human xenograft. These diseased mice are useful in the study of endometriosis. Excerpt(s): This invention relates to an endometriosis mouse model wherein severely compromised immune deficient (SCID) female mice are transplanted with human xenografts of normal endometrial tissue, but result in mice with human endometriosis tissue. These diseased mice are useful in the study of endometriosis, in particular to identify nucleic acid sequences or amino acid sequences that up- or down- regulate the diseased state, or that are endometriosis specific. Endometriosis is a disease affecting women of reproductive age, causing substantial debilitation, such as pelvic pain, and possible sterility or infertility, depending upon the severity of the condition. Most experts agree that endometriosis originates from retrograde menstruation of normal endometrial fragments that then implant on to peritoneal surfaces, from vascular or lymphatic dissemination of endometriosis lesions to other parts of the body, and/or from metaplasia, i.e., the abnormal transformation of one differentiated tissue into another. Modem Approaches to Endometriosis., eds. E. Thomas and J. Rocky, Kluwer Academic Publishers Boston (1991). Typically, diagnosing endometriosis requires an invasive procedure, which results in the possibility of infection and other disadvantages associated with surgery. At present, the most effective therapy for treatment of endometriosis is surgical intervention, along with the administration of growth factor antagonists; ovarian suppression treatments, such as gonadotropin-releasing hormone (GnRH) agonists; and immunomodulators to inhibit the implantation of endometrial cells into undesired tissues. Therefore, it is desirable to develop procedures, techniques, and treatments that are easier to use and are more effective in the diagnosis and/or treatment of the disease. Web site: http://www.delphion.com/details?pn=US06429353__
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Hexahydropyrazolo[4,3,-c]pyridine metabolites Inventor(s): Khojasteh; S. Cyrus (Berkeley, CA), O'Donnell; John P. (N. Stonington, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,531,449 Date filed: March 8, 2001 Abstract: The invention provides metabolites of the compound 2-amino-N-[2-(3a(R)benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1-(R)benzyl-oxymethyl-2-oxo-ethyl]-isobutyramide, the racemic-diastereomeric mixtures and optical isomers thereof, the prodrugs thereof, and the pharmaceutically acceptable salts of the metabolites, racemic-diastereomeric mixtures, optical isomers, and prodrugs; to pharmaceutical compositions thereof; and to methods of using the metabolites and the compositions in the treatment of diseases associated with reduced levels of growth hormone.The invention further provides a kit comprising a metabolite of the compound 2-amino-N-[2-(3a(R)-benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3c]pyridin-5-yl)-1-(R)-benzyl-oxymethyl-2-oxo-ethyl]-isobutyramide a racemicdiastereomeric mixture or optical isomer thereof, a prodrug thereof, or a pharmaceutically acceptable salt of the metabolite, racemic-diastereomeric mixture, optical isomers, or prodrug, and a pharmaceutically acceptable carrier, vehicle or diluent in a first unit dosage form; estrogen, progesterone, Premarin.RTM., or a bisphosphonate compound, preferably alendronate, and a pharmaceutically acceptable carrier, vehicle or diluent in a second unit dosage form; and a container. Excerpt(s): The invention relates to metabolites of the compound 2-amino-N-[2-(3a(R)benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1-(R)benzyl-oxymethyl-2-oxo-ethyl]-isobutyramide, pharmaceutical compositions thereof, and to methods of using the metabolites and the pharmaceutical compositions in the treatment of diseases associated with reduced levels of growth hormone. (3) increased mobilization of free fatty acids and use thereof for energy. Deficiency in growth hormone production results in a variety of medical disorders. In children, it causes dwarfism. In adults, the consequences of acquired GH deficiency include profound reduction in lean body mass and concomitant increase in total body fat, particularly in the truncal region. Decreased skeletal and cardiac muscle mass and muscle strength lead to a significant reduction in exercise capacity. Bone density is also reduced. Administration of exogenous GH has been shown to reverse many of these metabolic changes. Additional benefits of therapy have included reduction in LDL cholesterol and improved psychological well-being. Web site: http://www.delphion.com/details?pn=US06531449__
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Hormone response element that binds an androgen and progesterone receptor Inventor(s): Haendler; Bernhard (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 6,518,041 Date filed: November 22, 1999 Abstract: The invention relates to a novel HRE (hormone response element) which binds to an androgen or progesterone regulated receptor.
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Excerpt(s): The invention relates to a new HRE (hormone response element, hormone receptor binding site), which is bonded by an androgen and progesterone receptor, its sequence and its use. Steroid receptors are transcription factors that have a ligand binding site, a DNA binding site and several transactivation functions. If the ligand binds the steroid, the conformation of the receptor changes. By this change in conformation, the receptor can form a dimer and bind to a specific, two-stranded DNA sequence, the so-called HRE (hormone response element, hormone receptor binding site) and interact with coactivators and other transcription factors. As a consequence, the transcription of the target gene, thus the gene that is regulated by the HRE, is activated. These HREs are usually components of promoter regions of such target genes, but they can also be found in the intron areas or in the 3'-part of the gene. For the HRE of the androgen receptor, a consensus sequence (SEQ ID NO: 4) GG(T/A)ACAnnnTGTTCT has been found (Roche et al. 1992, Mol. Endocrinol. 6, 2229-2235). In this case, n refers to any nucleotide. The half-elements, which are the defined nucleotides before or after the "nnn" sequence, are approximately palindromic. It was shown that the sequence (SEQ ID NO: 5) GGTACAtctTGTTCA, which occurs in the promoter of the highly androgenregulated CRISP-i-gene, has a high binding affinity to the androgen receptor (Schwidetzky et al. 1997, Biochem. J. 321, 325-332). This sequence is referred to in the following consensus-HRE. It is detected, however, not only by the androgen receptor but also by the glucocorticoid and progesterone receptor. The HRE, however, binds the promoter region of the probasin gene selectively to the androgen receptor and not to the glucocorticoid receptor (F. Claessens et al. 1996, J. Biol. Chem. 271, 19013-19016). No information on the binding of the progesterone receptor is present here. By an in vitro selection method, a new DNA sequence named IDR17, which can bind the androgen receptor, was recently found (Zhou et al. 1997, J. Biol. Chem. 272, 8227-8235). Various tests showed that this sequence has a high selectivity for the androgen receptor in comparison to the glucocorticoid receptor. A comparison with the progesterone receptor was not described. The sequence IDR17 is a sequence that was found in vitro; there is no indication as to whether it also occurs in vivo and has a function there as an HRE. The knowledge on HREs is helpful in the development of medications for the treatment of hormone-dependent diseases. In the treatment of prostate cancer with antiandrogens, which inhibit the binding of the androgen receptor to the consensus HRE, it is frequently shown that not all androgen-regulated genes are adjusted downward and/or the antiandrogens are no longer active after a certain treatment time. These findings thereupon point to the fact that different HREs must be provided that regulate various genes and are responsible for the hormone-dependency. For successful hormone therapy, it is therefore desirable to know other HREs to which the androgen receptor binds. Specifically active natural hormones, synthetic hormones or antihormones could then be identified. The latter can then turn on or off the genes that are relevant for the diseases. To date, only a few genes that are regulated by androgens and their HREs are known. Examples of this are the probasin gene and the C3(1) gene, which are both induced in rat prostates by androgen (F. Claessens et al. 1989, Biochem. Biophys. Res. Commun. 164, 833-840; P. S. Rennie et al. 1993, Mol. Endocrinol. 7, 23-36). In the rat epididymis, the pem gene is expressed in an androgen-dependent manner (S. Malti et al. 1996, J. Biol. Chem. 271, 17536-17546). The approximate position of two initial transcription sites is described, but the HRE is not known. Web site: http://www.delphion.com/details?pn=US06518041__
Patents 155
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Hormone-secreting cells maintained in long-term culture Inventor(s): Brothers; Ann Janice (Fairfax, CA) Assignee(s): Pacific Biomedical Research, Inc. [Cell Mart, Inc.] (Reno, NV) Patent Number: 6,372,493 Date filed: April 28, 1999 Abstract: Methods are provided for the establishment and maintenance in long term culture of hormone secreting cells. Cells are derived from tumorous or non-tumorous animal or human tissues, including ovary, endometrium, trophoblast, pituitary, thyroid, and pancreas. The cells secrete into the culture medium hormones such as estrogens, progestins, follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotrophin, thyroxin, glucagon, and insulin, depending on the tissue of origin of individual cell cultures. Contact with an appropriate secretogogue causes the cells to respond with increased hormone secretion. For instance, ovarian follicular cells respond to follicle-stimulating hormone with increased estrogen and progesterone secretion. Pancreatic cells respond to elevated glucose with increased insulin secretion. The cells proliferate in in vitro for up to one year or longer, during which time they retain their hormone-secretion profile. The cells may be frozen for storage, and retain their hormone-secretion profile after thawing. The cell cultures are useful for the production of human hormones, for the bio-assay of drugs such as therapeutic gonadotrophin, for the testing of drug efficacy and design, and for toxicity testing of drugs and chemicals. The cells may also be implanted in an individual to replace deficient hormone secretion. For instance, insulin secreting pancreatic cells may be implanted in a diabetic individual as an adjunct or replacement therapy for exogenously administered insulin. Excerpt(s): The invention relates to long-term proliferating in vitro cultures of hormonesecreting cells and to methods for establishing, maintaining, and propagating hormonesecreting cells in culture. Hormone-secreting cells are highly differentiated and specialized for the synthesis and secretion of typically one or two specific hormones. Examples of hormone-secreting cells include certain cells of the pituitary gland, the endometrium, the ovary and the pancreas. The pituitary gland contains cells specialized for the synthesis and secretion of glycoprotein hormones known as gonadotrophins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which act on the gonads. The gonadotrophins secreted by the pituitary enter the blood stream and reach the gonads, where they exert their affects. Within the ovary, upon stimulation with gonadotrophins, granulosa cells surrounding an ovum differentiate within the preovulatory follicle to synthesize and secrete estrogen and progesterone. Specialized cells of the endometrium also synthesize and secrete estrogen and progesterone. Within the pancreas,.beta.-cells of the islets respond to increased blood glucose concentration with an increase in insulin secretion. Conventional cell culture technology is sufficient for the propagation of certain cell types in vitro such as fibroblasts taken from normal tissue or from tumors. It has long been a goal of scientists to maintain hormonesecreting cells in vitro, however standard culture conditions do not promote the longterm survival or proliferation of hormone-secreting cells. For practical purposes, it would be desirable to establish in culture cells which both proliferate and perform their specialized functions, i.e., synthesis and secretion of specific hormones. Web site: http://www.delphion.com/details?pn=US06372493__
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Intra-vaginal device for pigs Inventor(s): Burccraff; Shane (Hamilton, NZ), Pharaoh; James Frederick (Hamilton, NZ), Rathbone; Michael John (Hamilton, NZ) Assignee(s): Interag (Hamilton, NZ) Patent Number: 6,444,224 Date filed: March 2, 2000 Abstract: Disclosed herein is a porcine intra-vaginal device of a shape and size adapted to be positionable in the vaginal tract across the hymenal ring of a target animal (e.g., a gilt) to extend to both sides of the hymenal ring of the animal. The device once inserted delivers progesterone from a progesterone impreganated matrix on either side of the hymenal ring, the progesterone releasing surface being at least 150 cm.sup.2 in total area. Variable geometry means (preferably for vestibular engagement) ensure retention of the devices (e.g., for at least 7 to 14 days) where, in the preferred device, the progesterone load of from 1.9 to 2.5 g within 1.2 mm of the release surface can, by maintaining a progesterone blood plasma level (equating to a progestrone blood plasma level in excess of 4 ng/mL measured in an ovariectomised animal), ensure or prompt the onset of oestrus within 3 to 5 days after device removal. Excerpt(s): This application is a 371 of PCT/N298/00064 filed May 27, 1998. The present invention relates to improvements in and/or relating to intra-vaginal devices suitable for insertion and retention within pigs. Intra-vaginal devices are frequently used to deliver an active substance into an animal. Web site: http://www.delphion.com/details?pn=US06444224__
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Method of making nanoparticles of substantially water insoluble materials Inventor(s): Hassan; EmadEldin M. (Coventry House, Apt. B2 8048 Oxford Ave., Philadelphia, PA 19111) Assignee(s): none reported Patent Number: 6,623,761 Date filed: December 22, 2000 Abstract: This invention relates to a novel process of manufacture of nanoparticles of substantially water insoluble materials from emulsions. The emulsions have the ability to form a single liquid phase upon dilution of the external phase, instantly producing dispersible solid nanoparticles. The formed nanoparticles have average diameter of about 10 to 200 nm and are suitable for drug delivery and targeting of water insoluble therapeutic or diagnostic agents. Examples of such agents are methotrexate, progesterone, testosterone, prednisolone, and ibuprofen. Such agents can be used in a wide range of therapeutic and diagnostic treatments including treatment for cancer, hormonal therapy, and pain management. Excerpt(s): This invention relates to nanoparticles of substantially water insoluble materials, methods of preparation, and use thereof. In particular, the invention relates to nanoparticles of therapeutic and diagnostic agents, method of preparation thereof, and pharmaceutically useful dispersions containing these nanoparticles. This invention further relates to methods of treatment using these nanoparticles. Nanoparticles of substantially water insoluble materials (i.e. materials that have water solubility of less than 0.1%) have a wide variety of applications, including therapeutic and diagnostic
Patents 157
agents, paints, inks, dyes, and semiconductors. In most cases, performance of these nanoparticles dramatically improves as the nanoparticle size is reduced to 200 nanometers or less. Nanoparticles of therapeutic and diagnostic agents, in particular of a pharmaceutical compound ("drug") are customarily delivered with a solid or liquid carrier. Liquid containing nanoparticles such as emulsions, microemulsions and liposomes, however, usually suffer from the inherent physical instability of fluids resulting from globule dissociation. Solid polymeric or lipid nanoparticles have more structural stability, yet the rate of biodegradation of the nanoparticles and/or controlled release of the agent in the nanoparticles may not take place as intended, thereby adversely affecting optimal agent delivery and targeting. In addition, only a relatively small amount of the agent or drug can be encapsulated in fluid or solid carriers, requiring large, and sometimes impractical size dosages. Carrier-free nanoparticles, made entirely of a water insoluble therapeutic agent or drug, have been introduced as an alternative solution for the above limitations and drawbacks. There are two major techniques described in the prior art, to produce solid drug nanoparticles. These techniques are known as wet grinding, and antisolvent precipitation. Other general techniques for nanoparticle formation, such as solvent evaporation and emulsion polymerization, are either not suitable or have not proved to be successful in making carrier-free drug nanoparticles. Web site: http://www.delphion.com/details?pn=US06623761__ •
Method of treating inflammatory conditions with progesterone analogs Inventor(s): Schreiber; Alan D. (Philadelphia, PA) Assignee(s): University of Pennsylvania (Philadelphia, PA) Patent Number: 6,610,674 Date filed: September 8, 2000 Abstract: The present invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis, using progesterone or progesterone analogs such as medroxyprogesterone acetate. Excerpt(s): This invention provides methods for treating inflammatory conditions, including but not limited to, inflammatory bowel disease (ulcerative colitis, Crohn's disease, and proctitis), other noninfectious, inflammatory conditions of the GI tract (microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, pill induced esophagitis, celiac disease, recurrent polyps, and hemorrhoids), and psoriasis using progesterone and progesterone analogs. Proctitis, inflammation of the rectum, is invariably present in UC and is sometimes present in CD. It may also occur independently from these diseases. Proctitis is another manifestation of IBD with pathology similar to UC. A patient presenting with proctitis may later develop fullblown UC or CD. Physicians and medical researchers have not been successful in identifying a cause for these diseases, although several theories have been postulated. The diseases may be caused by a pathogen or other antigen that initiates the inflammatory response in the bowel, accompanied by a defect in the ability to downregulate the immune response. Once initiated, many of the pathophysiological events in IBD are related to amplification of the inflammatory process. In response to antigens, cytokines and other inflammatory mediators are released. Some cytokines promote T
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cell activity. The inflammatory cascade continues with IL-2, helper T cells, B-cell proliferation, and antibody synthesis. Stimulated neutrophils and macrophages accumulate and further damage the tissue by releasing reactive oxygen species and other biologically active products. Additional acute inflammatory cells respond to the tissue damage, whether or not the primary initiating stimulus has ceased. Web site: http://www.delphion.com/details?pn=US06610674__ •
Pharmaceutical composition with a synthetic natural progesterone and oestradiol base and its preparation process Inventor(s): Agnus; Benoit (Bry sur Marne, FR), Besins; Antoine (Paris, FR) Assignee(s): Laboratoires Besins Iscovesco (Paris, FR) Patent Number: 6,656,929 Date filed: March 16, 1999 Abstract: The object of this invention is a pharmaceutical composition with a synthetic natural progesterone and oestradiol base coming in the form of a tablet, characterised by the fact that it has a disintegration time of less than 15 minutes, preferably less than 10 minutes, and more preferably still less than 5 minutes. Excerpt(s): The object of the present invention is a pharmaceutical composition with a synthetic natural progesterone and oestradiol base coming in the form of a tablet, as well as a method for its preparation. In the context of the present invention, "synthetic natural progesterone" is understood to mean a synthesized progesterone the chemical formula of which corresponds to the "natural" progesterone, such as is found in the female body. On the other hand, "synthetic progestagens" are entirely synthetic molecules such as trimegestone, norethisterone and others, the structure of which does not correspond to that of the natural progesterone. Menopause in women can cause, indeed aggravate, certain pathologies such as oesteoporosis or cardiovascular illnesses. Web site: http://www.delphion.com/details?pn=US06656929__
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Pharmaceuticals for modulating hormone responsiveness Inventor(s): Dedhar; Shoukat (#1-219 East 8th St., North Vancouver B.C., CA V7L 1Y9) Assignee(s): none reported Patent Number: 6,518,397 Date filed: July 24, 1997 Abstract: This invention relates to isolated and purified proteins, such as calreticulin and mimetics and inhibitors of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease. The proteins include or bind to an amino acid sequence [SEQ ID NO: 1] KXFFX.sup.1 R, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins
Patents 159
which include this sequence may promote hormone receptor induced gene transcription. Excerpt(s): The physiology of many organs in mammals is regulated by hormones. These hormones include steroid hormones, thyroid hormones, metabolites of vitamins, such as all trans retinoic acid, 9-cis retinoic acid, vitamin D and its metabolite 1,25 dihydroxyvitamin D3. These hormones bind to intracellular receptors which regulate expression of genes (O'Malley, 1990). There are a variety of receptors which respond to hormones. Osteoblasts and osteoclasts respond to steroid hormones, vitamin D and retinoic acid. Mammary epithelial cells and breast carcinoma cells respond to estrogens, progesterone, retinoic acid and glucocorticoids. Lymphocytes respond to glucocorticoids. The response of receptors to hormones is particularly important in the development of a number of diseases, including cancer, osteoporosis and chronic inflammatory disease. For example, the vitamin D receptor is strongly implicated in the evolution of osteoporosis (Morrison, 1994). Web site: http://www.delphion.com/details?pn=US06518397__ •
Progesterone antagonists for the production of pharmaceutical agents for the treatment of dysfunctional uterine bleeding Inventor(s): Chwalsz; Kristof (Berlin, DE), Stockemann; Klaus (Berlin, DE) Assignee(s): Schering Aktiengesellschaft (Berlin, DE) Patent Number: 6,451,780 Date filed: July 12, 2000 Abstract: Competitive progesterone antagonists (antigestagens) are suitable for the production of pharmaceutical agents for the treatment of forms of dysfunctional uterine bleeding (metrorrhagias, menorrhagias, hypermenorrhea). Excerpt(s): This invention relates to the use of at least one compound with a progesterone-antagonistic (PA) action for the production of pharmaceutical agents for the treatment of dysfunctional uterine bleeding. Forms of dysfunctional uterine bleeding (dysfunctional or abnormal uterine bleeding, metrorrhagias and menorrhagias, hypermenorrhea) are forms of pathological bleeding that are not attributable to organic changes in the uterus (such as, e.g., endometrial carcinoma, myomas, polyps, etc.), systemic coagulation disorders, or a pathological pregnancy (e.g., ectopic pregnancy, impending abortion) (American College of Obstetricians and Gynecologists, 1982). The average blood loss during normal menstruation is about 30 ml, whereby the period lasts for an average of 5 days. If the blood loss exceeds 80 ml, it is classified as pathological (Zahradnik HP, (1992) Menstruation. In Kaser O et al. (editors) Gynakologie und Geburtshilfe [Gynecology and Obstetrics], Vol. 1/2, Georg Thieme Verlag Stuttgart, New York: 7.31-7.51). Web site: http://www.delphion.com/details?pn=US06451780__
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Synchronizing of animal oestrus and intra vaginal devices useful therein Inventor(s): Bunt; Craig Robert (Hamilton, NZ), Burggraaf; Shane (Hamilton, NZ), Rathbone; Michael John (Hamilton, NZ) Assignee(s): Interag (Hamilton, NZ) Patent Number: 6,423,039 Date filed: October 30, 1998 Abstract: An intra vaginal device which is of a variable geometry and which includes a silicone matrix impregnated with progesterone, the confirmation and content of the progesterone impregnated matrix being such as to optimize effectiveness with a lower initial loading of progesterone. Excerpt(s): The present invention relates to improvements in and/or relating to the synchronising of animal oestrus and intra vaginal devices useful therein together with related means and methods. It is useful for farmers to synchronise the oestrus of animals whether they be cattle beasts (whether for dairy or beef purposes) sheep, goats, horses, or the like where artificial insemination is practised. By way of example, in relation to cattle beasts, in a normal 365 day year 282 days on average is taken up of the year with the gestation period itself. With approximately 30 days to recover after delivery of its progeny each cow therefore has an average of only two and a half cycles if there is to be a timely management of the herd. Thus it is important over that remaining period of less than 53 days to ensure each cow in a herd becomes pregnant. The traditional method of mating dairy cows with bulls is now largely superseded by the use of artificial insemination procedures which offer the prospect of rapid herd improvements although bulls are still presented to the herd frequently to catch those animals that have not conceived by the artificial insemination procedure. Web site: http://www.delphion.com/details?pn=US06423039__
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System for thermometry-based breast assessment including cancer risk Inventor(s): Jenkins; Kevin (1 The Croft, Marsh Baldon, Oxfordshire OX44 9LN, GB), Young; Colin Alfred (20 North Quay, Abingdon Marina, Abingdon, Oxfordshire, OX14 5RY, GB), Young; David Ernest (Bowler's Piece, 16 Couching Street, Watlington, Oxfordshire OX49 5QQ, GB) Assignee(s): none reported Patent Number: 6,419,636 Date filed: November 9, 2000 Abstract: A system for thermometry-based breast assessment has an analog electronic sensor and an adjustable mechanical harness. In order to sample breast surface temperature, and to collect, store, and display data relating thereto, the system has remote data-logging control. The system allows breast temperatures to be measured, with great accuracy and reliability, for selected periods for up to seven days at any desired rational sampling rate. Collected breast surface temperature data may then be uploaded into a computer for elaboration using a dedicated computer program. Breast surface temperatures may be measured at a specific point during the menstrual cycle, determined by progesterone levels in the urine when the system is used to determine the risk of breast cancer occurring later in women who do not currently have the disease or it may be used at other times for other purposes.
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Excerpt(s): The present invention is in the field of biotechnology and specifically relates to the field of breast assessment and breast cancer screening in women. For well over twenty years, thermometric assessment of the human female breast surface has been under investigation as a tool in the armamentarium of those concerned with the detection and treatment of breast cancer. In a subsequently abandoned application publication number GB 2,203,250 A, Simpson again teaches a garment in the form of a brassiere with a miniaturized electronic heat measuring device which has a number of cup temperature sensors. In a further embodiment there is disclosed another brassiere "having a single sensor net of high thermal conductivity wire centered on the nipple and extending for a few centimeters around each nipple". Web site: http://www.delphion.com/details?pn=US06419636__ •
Testing method Inventor(s): Lamming; G. Eric (Melton Mowbray, GB) Assignee(s): Milk Development Council (GB), University of Nottingham (GB) Patent Number: 6,602,676 Date filed: April 7, 2000 Abstract: This invention relates to a method of predicting pregnancy, particularly, in a cow, the method comprising taking a milk sample from the cow in which a milk progesterone concentration of >3 ng ml.sup.-1 by Day 4 post insemination is indicative that the animal is pregnant. The invention also relates to methods of improving pregnancy success by timely supply of progesterone or a functional equivalent thereof (progestagen); to methods of assessing suitability for progesterone replacement therapy; and to methods of embryo transfer. Excerpt(s): This invention relates to a method of testing and is particularly though not exclusively concerned with a method of testing progesterone levels and pregnancy in cows. Reproductive performance is one of the important factors determining the profitability of dairy herds. Ideally, the calving interval should average one year, but this can only be achieved if the pregnancy success and detection of oestrous rates are high and the interval between parturition and first service is less than 90 days (Bulma, D. C. and Lamming G. E. J Reprod. Fert (1978) 54: 447-58). The basic physiology of pregnancy in cows is relatively well understood. Following ovulation, the release of an oocyte for fertilisation, which usually occurs 6-12 hours after the end of oestrous (occasionally up to 36 hours later), the rapidly growing corpus luteum (CL) is formed from follicular cells remaining in the ovary. One of the main functions of the CL is to secrete the steroid hormone progesterone (P.sub.4). During a normal 21-day oestrous cycle an animal shows measurable P.sub.4 levels between days 4-19 post oestrous and following the demise of the CL a period of 6 to 7 days with low P.sub.4 concentrations. Web site: http://www.delphion.com/details?pn=US06602676__
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Patent Applications on Progesterone As of December 2000, U.S. patent applications are open to public viewing.10 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 progesterone: •
17-Side chain alkynyl-and 20-oxopregna-derivatives of vitamin D, methods for their production and pharmaceutical compositions thereof Inventor(s): Hesse, Robert Henry; (Winchester, MA), Pechet, Maurice Murdoch; (Cambridge, MA), Setty, Sundara Katugam Srinivasasetty; (Cambridge, MA) Correspondence: Richard E. Fichter; Bacon & Thomas, Pllc; Fourth Floor; 625 Slaters Lane; Alexandria; VA; 22314-1176; US Patent Application Number: 20020188142 Date filed: March 7, 2002 Abstract: 1-Hydroxy pregnacalciferol derivatives of formula (I) and their corresponding 5,6-trans isomers wherein R.sup.1 is hydroxyl or lower alkoxy and R.sup.2 is optionally hydroxylated or lower alkoxylated lower alkynyl and R.sup.1 is C(R.sup.A) (R.sup.B)CH.sub.3 where R.sup.A is optionally hydroxylated or lower alkoxylated lower alkynyl and R.sup.B is hydroxyl or lower alkoxy or R.sup.A and R.sup.B together represent oxo and R.sup.2 is hydrogen, hydroxyl or lower alkoxy, and R.sup.3 and R.sup.4 represent hydrogen atoms, exhibit anti-progesterone activity and may be useful as antineoplastic, antifertility, antiproliferative, immunosuppressive and/or antiinflammatory agents. Excerpt(s): This invention relates to new 1-hydroxy pregnacalciferol derivatives, more especially to 1-hydroxy pregnacalciferol derivatives having anti-progesterone activity. Vitamin D.sub.3 has long been known to play a key role in the metabolism of calcium. The discovery that the D vitamins undergo hydroxylation in vivo led to the synthesis of many analogues of vitamin D whose evaluation indicated that hydroxyl groups at the 1.alpha.-position and at either the 24R- or 25-position were essential for the compound or metabolite thereof to exhibit a substantial effect on calcium metabolism. Subsequent work indicated that the natural metabolite 1.alpha., 25-dihydroxy vitamin D.sub.3 exhibited-cell modulating activity, including stimulation of cell maturation and differentiation, as well as immunosuppressive effects, and also exhibited an immunopotentiating effect, stimulating the production of bactericidal oxygen metabolites and the chemotactic response of leukocytes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Beta-catenin is a strong and independent prognostic factor for cancer Inventor(s): Hung, Mien-Chie; (Houston, TX), Lin, Shiaw-Yih; (Houston, TX), Xia, Weiya; (Missouri City, TX) Correspondence: Fulbright & Jaworski L.L.P.; Melissa L. Sistrunk; Suite 5100; 1301 Mckinney; Houston; TX; 77010-3095; US Patent Application Number: 20030064384 Date filed: April 2, 2002 Abstract: Cyclin D1 is one of the targets of.beta.-catenin in breast cancer cells. Transactivation of.beta.-catenin correlated significantly with cyclin D1 expression both in eight breast cell lines in vitro and in 123 patient samples. More importantly, high.beta.-catenin activity significantly correlated with poor prognosis of the patients and is a strong and independent prognostic factor in breast cancer (p<0.001). Moreover, by multivariate analyses, the inventors found that activated.beta.-catenin is a strong prognostic factor which provided additional and independent predictive information on patients survival rate even when other prognostic factors, including lymph node metastasis, tumor size, estrogen receptor and progesterone receptor status, were taken into account (p<0.001). This invention demonstrates that.beta.-catenin is involved in breast cancer formation and/or progression and may serve as a target for breast cancer therapy. Excerpt(s): This application claims priority to United States Provisional Patent Application Serial No. 60/281,108 filed Apr. 2, 2001, incorporated by reference herein in its entirety. The present invention relates generally to the field of cancer prognostics. More particularly, it provides compositions and methods for use as a prognostic marker for cancer. Cancer is a serious health issue for millions of individuals. Breast cancer is the most common form of cancer occurring in females in the US with the incidence of breast cancers in the United States projected to be 192,200 cases of invasive breast cancer diagnosed and 40,600 breast cancer-related deaths to occur in 2001 (American Cancer Society statistics). Estimates indicate that one in eight women who reach the age of 85 will develop breast cancer (American Cancer Society, Atlanta Ga., 1994, p. 13). Furthermore, ovarian cancer affects many women and includes three basic types: epithelial carcinoma, germ cell cancer, and stromal cell cancer. The most common kind of ovarian tumor is epithelial carcinoma, which starts in the epithelial cells found in the outer layer of cells in the ovaries. The second type of ovarian cancer is germ cell cancer, which starts in the cells that form eggs in the ovary. Only about 5 percent of ovarian cancers are germ cell cancer. Finally, stromal cell ovarian cancer begins in the stromal cells, which produce female hormones and form the tissue that holds the ovaries together. Only about 5 percent of all ovarian cancer is stromal cell cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Bicyclic androgen and progesterone receptor modulator compounds and methods Inventor(s): Farmer, Luc; (Foxborough, MA), Hamann, Lawrence G.; (Cherry Hill, NJ), Higuchi, Robert; (Solana Beach, CA), Martinborough, Esther; (San Diego, CA), Motamedi, Mehrnouch; (San Diego, CA), Pio, Barbara; (San Diego, CA), Tegley, Christopher; (San Diego, CA), Van Oerveren, Cornelis Arjan; (San Diego, CA), West, Sarah; (San Diego, CA), Zhi, Lin; (San Diego, CA) Correspondence: Richard H. Pagliery; Brobeck, Phleger & Harrison Llp; 12390 EL Camino Real; San Diego; CA; 92130-2081; US Patent Application Number: 20030130505 Date filed: November 18, 2002 Abstract: The present invention is directed to compounds, pharmaceutical compositions, and methods for modulating processes mediated by AR and PR. More particularly, the invention relates to nonsteroidal compounds and compositions that are high affinity, high specificity agonists, partial agonists (i.e., partial activators and/or tissue-specific activators) and antagonists for AR and PR. Also provided are methods of making such compounds and pharmaceutical compositions, as well as critical intermediates used in their synthesis. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/150,987, filed Aug. 27, 1999, the entire disclosure of which is incorporated by reference herein. This invention relates to nonsteroidal compounds that are modulators (i.e., agonists, partial agonists and antagonists) of androgen and progesterone receptors, and to methods for the making and use of such compounds. Intracellular receptors (IRs) form a class of structurally-related genetic regulators scientists have named "ligand dependent transcription factors" (R. M. Evans, Science, 240:889, 1988). Steroid receptors are a recognized subset of the IRs, including androgen receptor (AR), progesterone receptor (PR), estrogen receptor (ER), glucocorticoid receptor (GR), and mineralocoticoid receptor (MR). Regulation of a gene by such factors requires both the IR itself and a corresponding ligand, which has the ability to selectively bind to the IR in a way that affects gene transcription. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination preparation for contraception based on naural estrogens Inventor(s): Dittgen, Michael; (Apolda, DE), Fricke, Sabine; (Jena, DE), Hoffmann, Herbert; (Jena, DE), Moore, Claudia; (Jena, DE), Oettel, Michael; (Jena, DE), Ostertag, Monika; (Gottingen, DE) Correspondence: Striker, Striker & Stenby; 103 East Neck Road; Huntington; NY; 11743; US Patent Application Number: 20020107229 Date filed: September 12, 2001 Abstract: The combination preparation for contraception includes from 2 to 4 first stage daily dosage portions each including an effective amount of at least one natural estrogen as sole active ingredient, from 16 to 22 second stage daily dosage portions each including an effective amount of a combination of at least one natural estrogen and at least one natural or synthetic gestogen as active ingredient; from 2 to 4 third stage daily dosage portions each including an effective amount of at least one natural estrogen as
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sole active ingredient; and from 2 to 4 final stage daily dosage portions containing a pharmaceutically acceptable placebo. The estrogen may be estradiol, an estradiol compound that is metabolized to estradiol when taken into the body, a conjugated equine estrogen or a phytoestrogen. The natural or synthetic gestogen can be natural progesterone or a synthetic gestogens, such as medroxyprogesterone acetate. Excerpt(s): The present invention relates to a multistage contraceptive preparation based on natural estrogens. Oral contraceptives were first marketed 60 years ago. By continuous research it has been possible to reduce the required dosages of hormones in a stepwise manner. Currently low dosage oral contraceptives exist which chiefly comprise an estrogen component and a gestogen component. The hormone dosage of these contraceptives is delivered in different combinations and dosages in the form of combination preparations (one-stage preparation) or multistage combination preparations (staged preparations) and sequenced preparations (two-stage preparations) over time periods of from 21 to 28 days. One-stage preparations (usually designated as combination preparations) are characterized by a constant dosage of certain estrogens and gestogens each day. Because of the uniform delivery of gestogen ingredients with estrogen components from the first application day, the combination preparation is a highly reliable contraceptive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions for preventing hormone induced adverse effects Inventor(s): Levy, Joseph; (Omer, IL), Sharoni, Yoav; (Omer, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030004146 Date filed: March 5, 2001 Abstract: A unit dosage form suitable for once daily administration to a human comprising a physiologically effective amount of at least one hormone selected from the group consisting of steroidal estrogen, estradiol, estrone, medroxyprogesterone, norethindrone, norethisterone, progestin, norgestrel, and progesterone, and at least one carotenoid wherein said carotenoid is in an amount effective to prevent the adverse effects which may result from the administration of said hormone. Excerpt(s): The present invention provides compositions for preventing adverse effects associated with the administration of hormones such as phytoestrogens and steroidal estrogens. Hormone intake by humans can occur through, inter alia, consumption of pharmaceutical compositions, foodstuffs, nutritional supplements and nutraceuticals. Such hormones include phytoestrogens, or nonsteroidal estrogens, steroidal estrogens and progestins. Phytoestrogens comprise, for example, genistein, daidzein and glycitein, and their respective glucoside, malonylglucoside and acetylglucoside derivatives. Estrogens and progestins are known to be used for hormone replacement therapy (HRT) and in contraceptive medications. HRT with estrogens or with estrogen/progestin combinations has been the standard method for treating symptoms associated with menopause (Ernster VL et al. (1988) Benefits and Risks of Menopausal Estrogen and/or Progestin Hormone Use, Prev. Med. 17:201-223). The onset of menopause in mature adult women, which is accompanied by reduced estrogen production, is associated with an array of symptoms. These symptoms include hot and cold flashes, palpitations, dizziness, headaches, altered secretions as well as weight loss and gain. Reduced levels of circulating estrogen in post-menopausal women are also associated with increased
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risks of osteoporosis and coronary heart disease. Treatment protocols using estrogen alone significantly reduce the risks of cardiovascular disease and osteoporosis, if treatment begins at menopause. The protective effect of estrogen against heart disease is related to its ability to raise levels of circulating HDL and lower levels of LDL. In contrast with such beneficial effects, long-term use of estrogens is positively correlated with an increased risk for endometrial cancer development. This risk may be reduced by simultaneous administration of a progestin, which prevents overgrowth of endometrial cells. Hence, an estrogen/progestin combined HRT protocol is recommended for a woman with an intact uterus. This form of combination therapy however, apparently diminishes the beneficial effects of estrogen on the plasma lipid profile (Lobo R. 1992. The Role of Progestins in Hormone Replacement Therapy; Am. J Obstet. Gynecol. 166:1997-2004). Furthermore, some progestins are associated with an increased risk of mammary cancer development (Staffa J. A. et al. 1991. Progestins and Breast Cancer: An Epidemiologic Review, 57: 473-491; King R. J. B. 1991. A Discussion of the Roles of Estrogen and Progestin in Human Mammary Carcinogenesis, J. Ster. Biochem. Molec. Bio. 39:8111-8118). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Contraception method using competitive progesterone antagonists and novel compounds useful therein Inventor(s): Chwalisz, Krzystof; (Berlin, DE), Elger, Walter; (Berlin, DE), Ottow, Eckhard; (Berlin, DE), Schmidt-Gollwitzer, Karin; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030191102 Date filed: March 31, 2003 Abstract: Competitive progesterone antagonists, including two novel steroids, viz., 11.beta.,19-[4-(cyanophenyl)-o-phenylene]-17.beta.-hydroxy-17.alpha.-(3-h- ydroxyprop1(Z)-enyl)-4-androsten-3-one and 11.beta.,19-[4-(3-pyridinyl)-o- -phenylene]-17.beta.hydroxy-17.alpha.-(3-hydroxyprop-1(Z)-enyl)-4-androst- en-3-one, inhibit formation of endometrial glands at below their ovulation inhibiting dose and the abortive dose, and thus achieve oral contraception in females without adversely affecting the menstrual cycle and without risk of aborting a previous implanted fertilized egg or a fetus. Excerpt(s): This invention relates to a novel contraceptive method employing a competitive progesterone antagonist and to novel progesterone antagonists useful therein. By inhibiting the formation of endometrial glands and epithelium growth, the implantation of a fertilized egg in the uterus is rendered impossible (inhibition of the uterine receptivity). The employment of competitive progesterone antagonists according to the invention can thus be used for contraception in the female. RU 486 (11.beta.-[4-N,N-(dimethylamino)phenyl]-17.beta.-hydroxy-17.- alpha.-propinyl-estra4,9(10)-dien-3-one; EP-A-0057115) and other 11.beta.-aryl or 11.beta.,19-arylenesubstituted steroids are compounds which can displace progesterone and the glucocorticoids from their respective receptors. These substances are pharmacologically distinguished by strong progesterone- and glucocorticoid-antagonistic effects. These properties determine their previously practiced therapeutic uses. RU 486 is useful, e.g., as a progesterone antagonist for therapeutic termination of pregnancy and also as a glucocorticoid antagonist for treatment of Cushing's syndrome in the wake of a
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pathologically increased secretory activity of the suprarenal cortex. The abortive dose of RU 486 is 200-600 mg in the female. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Crystal Inventor(s): Carrondo, Maria Armenia; (Paco de Arcos, PT), Donner, Peter; (Berlin, DE), Egner, Ursula; (Berlin, DE), Matias, Pedro M.; (Porto Salvo, PT) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030167999 Date filed: September 9, 2002 Abstract: A crystal comprising an androgen receptor ligand binding domain (AR-LBD) is provided. The crystal structures of the human Androgen Receptor Ligand Binding Domain (hAR-LBD) in comparison with the human Progesterone Receptor Ligand Binding Domains (hPR-(hPR-LBD) complexed with the same ligand metribolone (R1881) are also provided. The three-dimensional structures of the hAR LBD as well as the hPR LBD show the typical nuclear receptor fold. The change of two residues in the ligand binding pocket (LBP) between hPR and hAR seems to be the most likely source for the specificity of the R1881 ligand binding to hAR LBD. The structural implications of the 14 known mutations in the LBP of the hAR LBD associated with either prostate cancer (PC) or the partial androgen receptor insensitivity syndrome (PAIS) or complete androgen receptor insensitivity syndrome (CAIS) are analysed. The effects of most of these mutants may be explained on the basis of the crystal structure. Excerpt(s): The present invention relates to a crystal structure. In particular, the present invention relates to a crystal structure for a ligand binding domain (LBD). In particular, the present invention relates to a crystal structure for a ligand binding domain (LBD) optionally having a ligand which is associated therewith. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cyanopyrroles Inventor(s): Collins, Mark A.; (Norristown, PA), Edwards, James P.; (San Diego, CA), Jones, Todd K.; (Solana Beach, CA), Mackner, Valerie A.; (Conshohocken, PA), Tegley, Christopher M.; (Thousand Oaks, CA), Wrobel, Jay E.; (Lawrenceville, NJ), Zhi, Lin; (San Diego, CA) Correspondence: Howson And Howson; One Spring House Corporation Center; Box 457; 321 Norristown Road; Spring House; PA; 19477; US Patent Application Number: 20030158182 Date filed: January 15, 2003 Abstract: This invention provides a progesterone receptor antagonist of formula 1 having the structure 1wherein T is O, S, or absent; R.sub.1, and R.sub.2 are each, independently, hydrogen, alkyl, substituted alkyl; or R.sub.1 and R.sub.2 are taken together form a ring and together contain --CH.sub.2(CH.sub.2).sub.nCH.sub.2--, -CH.sub.2CH.sub.2CMe.sub.2CH.sub.2- CH.sub.2--, --O(CH.sub.2)pCH.sub.2--, -O(CH.sub.2).sub.qO--, --CH.sub.2CH.sub.2OCH.sub.2CH.sub.2--, or --
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CH.sub.2CH.sub.2NR.sub.7CH.su- b.2CH.sub.2--;n=1-5; p=1-4; q=1-4;R.sub.3 is hydrogen, OH, NH.sub.2, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR.sup.A;R.sup.A is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sub.4 is hydrogen, halogen, CN, NH.sub.2, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sub.5 is hydrogen, alkyl, or substituted alkyl;R.sub.6 is hydrogen, alkyl, substituted alkyl, or COR.sup.B;R.sup.B is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl;R.sub.7 is hydrogen or alkyl, or a pharmaceutically acceptable salt thereof. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 10/043,513, filed Jan. 9, 2002, which is a divisional of U.S. patent application Ser. No. 09/552,544, filed April 19, 2000, now U.S. Pat. No. 6,407,161, which claims the benefit of the priority of U.S. Patent Application No. 60/183,050, filed May 4, 1999, now abandoned. Intracellular receptors (IR) form a class of structurally related gene regulators known as "ligand dependent transcription factors" (R. M. Evans, Science, 240, 889, 1988). The steroid receptor family is a subset of the IR family, including progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR). The natural hormone, or ligand, for the PR is the steroid progesterone, but synthetic compounds, such as medroxyprogesterone acetate or levonorgestrel, have been made which also serve as ligands. Once a ligand is present in the fluid surrounding a cell, it passes through the membrane via passive diffusion, and binds to the IR to create a receptor/ligand complex. This complex binds to specific gene promoters present in the cell's DNA. Once bound to the DNA the complex modulates the production of mRNA and protein encoded by that gene. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Dosage forms and methods for oral delivery of progesterone Inventor(s): Ho, Thomas Chun; (Irvine, CA), Hsia, David Chung; (Irvine, CA), Tan, Domingo Yap; (Irvine, CA), Weihmuller, Fredric C.; (Huntington Beach, CA) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030143276 Date filed: February 24, 2003 Abstract: Oral progesterone unit dosage forms comprising micronized progesterone and a solid polymeric carrier are provided. The dosage forms, upon oral administration, provide a therapeutically effective blood level of progesterone to a subject. The therapeutically effective blood level of progesterone may range from about 0.1 ng/ml to about 400 ng/ml. The dosage forms can be prepared for immediate as well as sustained release. The oral progesterone dosage form can be combined with an estrogen dosage form to provide combination hormone therapy. Excerpt(s): This application is a continuation of pending U.S. application Ser. No. 09/473,548, filed Dec. 28, 1999 the disclosure of which is hereby incorporated by reference in its entirety. This invention relates to oral dosage forms of hormones and methods for their delivery to subjects needing hormone therapy. Agnus et al., U.S. Pat. No. 6,086,916, col. 1, line 56- col. 2, line 4, discusses Gram [Novo Nordisk]WO 95/05807 as "describ[ing] tablets containing progesterone and a polyethylene glycol, as well as an excipient chosen from the group containing starches, starch-containing components,
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modified starches, celluloses, modified celluloses, pectins and tragacanth. [T]he presence of polyethylene glycol and of the excipient in the tablets results in a favourable effect on the bio-availability of orally administered progesterone. * * * [T]he tablets * * * contain high percentages of excipients." Gram's Abstract states that she provides an oral progeseterone that "may, conveniently, contain a PEG, and a further excipient selected from the group comprising a starch, a cellulose, pecting, and tragacanth." The polyethylene glycols are refrred to as "liquid or solid polymers". Page 7, lines 20-22. Examples with progesterone and estradiol include maize starch, lactose, polyethylene glycol 6000, croscarmellose sodium, magnesium stearate and taclum powder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Elemental nanoparticles of substantially water insoluble materials Inventor(s): Hassan, EmadEldin M.; (Philadelphia, PA) Correspondence: Dann Dorfman Herrell & Skillman; Suite 720; 1601 Market Street; Philadelphia; PA; 19103-2307; US Patent Application Number: 20020119916 Date filed: December 22, 2000 Abstract: This invention relates to a novel process of manufacture of nanoparticles of substantially water insoluble materials from emulsions. The emulsions have the ability to form a single liquid phase upon dilution of the external phase, instantly producing dispersible solid nanoparticles. The formed nanoparticles have average diameter of about 10 to 200 nm and are suitable for drug delivery and targeting of water insoluble therapeutic or diagnostic agents. Examples of such agents are methotrexate, progesterone, testosterone, prednisolone, and ibuprofen. Such agents can be used in a wide range of therapeutic and diagnostic treatments including treatment for cancer, hormonal therapy, and pain management. Excerpt(s): This invention relates to nanoparticles of substantially water insoluble materials, methods of preparation, and use thereof. In particular, the invention relates to nanoparticles of therapeutic and diagnostic agents, method of preparation thereof, and pharmaceutically useful dispersions containing these nanoparticles. This invention further relates to methods of treatment using these nanoparticles. Nanoparticles of substantially water insoluble materials (i.e. materials that have water solubility of less than 0.1%) have a wide variety of applications, including therapeutic and diagnostic agents, paints, inks, dyes, and semiconductors. In most cases, performance of these nanoparticles dramatically improves as the nanoparticle size is reduced to 200 nanometers or less. Nanoparticles of therapeutic and diagnostic agents, in particular of a pharmaceutical compound ("drug") are customarily delivered with a solid or liquid carrier. Liquid containing nanoparticles such as emulsions, microemulsions and liposomes, however, usually suffer from the inherent physical instability of fluids resulting from globule dissociation. Solid polymeric or lipid nanoparticles have more structural stability, yet the rate of biodegradation of the nanoparticles and/or controlled release of the agent in the nanoparticles may not take place as intended, thereby adversely affecting optimal agent delivery and targeting. In addition, only a relatively small amount of the agent or drug can be encapsulated in fluid or solid carriers, requiring large, and sometimes impractical size dosages. Carrier-free nanoparticles, made entirely of a water insoluble therapeutic agent or drug, have been introduced as an alternative solution for the above limitations and drawbacks. There are two major techniques described in the prior art, to produce solid drug nanoparticles. These
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techniques are known as wet grinding, and antisolvent precipitation. Other general techniques for nanoparticle formation, such as solvent evaporation and emulsion polymerization, are either not suitable or have not proved to be successful in making carrier-free drug nanoparticles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Growth hormone secretagogues Inventor(s): Carpino, Philip A.; (Groton, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030130284 Date filed: December 6, 2002 Abstract: This invention is directed to compounds of the formula 1and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintanence of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; a.beta.sub.3 adrenergic receptor agonist; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920. Excerpt(s): This invention relates to dipeptide compounds, which are growth hormone secretagogues and are useful for the treatment and prevention of musculoskeletal frailty including osteoporosis. 3. Increased mobilization of free fatty acids and use of fatty acids for energy. Deficiency in growth hormone results in a variety of medical disorders. In children, it causes dwarfism. In adults, the consequences of acquired GH deficiency include profound reduction in lean body mass and concomitant increase in total body fat, particularly in the truncal region. Decreased skeletal and cardiac muscle mass and muscle strength lead to a significant reduction in exercise capacity. Bone density is also reduced. Administration of exogenous growth hormone has been shown to reverse many of the metabolic changes. Additional benefits of therapy have included reduction in LDL cholesterol and improved psychological well-being. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Histological assessment Inventor(s): Hamer, Michael J.; (Malvern, GB), Kesidis, Anastaslos; (Guilford, GB), Petrou, Maria; (Guilford, GB) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030165263 Date filed: October 21, 2002 Abstract: A method of measuring oestrogen or progesterone receptor (ER or PR) comprises identifying in histopathological specimen image data pixel groups indicating cell nuclei, and deriving image hue and saturation. The image is thresholded using hue and saturation and preferentially stained cells identified. ER or PR status is determined from normalised average saturation and proportion of preferentially stained cells. A method of measuring C-erb-2 comprises correlating window functions with pixel subgroups to identify cell boundaries, computing measures of cell boundary brightness and sharpness and brightness extent around cell boundaries, and comparing the measures with comparison images associated with different values of C-erb-2. A C-erb-2 value associated with a comparison image having similar brightness-related measures is assigned. A method of measuring vascularity comprises deriving image hue and saturation, producing a segmented image by hue and saturation thresholding and identifying contiguous pixels. Vascularity is determined from contiguous pixel area corresponding to vascularity expressed as a proportion of total image area. Excerpt(s): This invention relates to a method, a computer program and an apparatus for histological assessment, and more particularly for making measurements upon histological imagery to provide clinical information on potentially cancerous tissue such as for example (but not exclusively) breast cancer tissue. Breast cancer is a common form of female cancer: once a lesion indicative of breast cancer has been detected, tissue samples are taken and examined by a histopathologist to establish a diagnosis, prognosis and treatment plan. However, pathological analysis of tissue samples is a time consuming and inaccurate process. It entails interpretation of colour images by human eye, which is highly subjective: it is characterised by considerable inaccuracies in observations of the same samples by different observers and even by the same observer at different times. For example, two different observers assessing the same ten tissue samples may easily give different opinions for three of the slides -30% error. The problem is exacerbated by heterogeneity, i.e. complexity of some tissue sample features. Moreover, there is a shortage of pathology staff. Oestrogen and progesterone receptor (ER and PR) status, C-erb-2 and vascularity are parameters which are data of interest for assisting a clinician to formulate a diagnosis, prognosis and treatment plan for a patient. C-erb-2 is also known as Cerb-B2, her-2, her-2/neu and erb-2. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibition of vascular smooth muscle cell proliferation Inventor(s): Haber, Carol; (Salisbury, NH), Haber, Edgar; (US), Lee, Wen-Sen; (Taipei, TW) Correspondence: Mintz, Levin, Cohn, Ferris, Glovsky; And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20020169151 Date filed: June 28, 2002 Abstract: Methods of treating a mammal having a condition characterized by vascular smooth muscle cell proliferation, where the mammal is treated with progesterone or an agonist thereof. Also disclosed are methods of screening compounds useful for inhibiting vascular smooth muscle cell proliferation. Excerpt(s): Under 35 USC.sctn.119(e)(1), this application claims the benefit of prior U.S. provisional application serial No. 60/044,651, filed Apr. 18, 1997. This invention relates to cardiovascular disease. Cardiovascular disease, the principal cause of death in the developed world, affects men far more frequently than premenopausal women of the same age. Because the incidence of cardiovascular disease in postmenopausal women gradually approaches that in age-matched men (McGill et al., Atheroscler. Rev. 4, 157242 (1979)), estrogen or progesterone appears to have a protective effect in premenopausal women. A large, 10-year prospective study supports such a cardioprotective effect of estrogen by showing that postmenopausal estrogenreplacement therapy reduces both the incidence of coronary heart disease and mortality from cardiovascular disease (Stampfer, M. J. et al., N. Engl. J. Med. 325, 756-762 (1991)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Intravaginal devices containing progesterone for estrus synchronization and related proceses Inventor(s): Dvoskin, Victor Oscar; (Lomas De Zamora, AR), Massara, Julio Eduardo; (Lomas De Zamora, AR), Massara, Nestor Gerardo; (Concaran, AR) Correspondence: Intervet Inc; 405 State Street; PO Box 318; Millsboro; DE; 19966; US Patent Application Number: 20030130558 Date filed: June 21, 2002 Abstract: Embodiments of the present invention generally relate to devices and processes related to estrus synchronization. Particular embodiments of devices and processes of the present invention slowly release progesterone over a period of time for estrus synchronization. Excerpt(s): The present application claims priority from an application filed in Argentina on Oct. 24, 2001, under application number P 01 01 04978. The present invention generally relates to devices and processes for estrus synchronization in an organism. Every period has specific nutritional requirements and hormonal characteristics. The pregnancy of the animals involves a substantial cost since the requirements of the last month of gestation are higher than those applicable to a nonpregnant animal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Kit for diagnosing non-pregnancy, and method for diagnosing non-pregnancy using the same Inventor(s): Cho, Min; (Kyonggi-do, KR), Kim, In Wook; (Kyonggi-do, KR), Seong, Hwan Hoo; (Seoul, KR), Won, Yoo Deok; (Kyonggi-do, KR) Correspondence: Staas & Halsey Llp; 700 11th Street, NW; Suite 500; Washington; DC; 20001; US Patent Application Number: 20020168781 Date filed: June 22, 2001 Abstract: The present invention relates to a kit for diagnosing non-pregnancy and a method for diagnosing non-pregnancy of an animal using the same, and more particularly, to a kit for diagnosing non-pregnancy of animal comprising: an assay strip, formed of thin film type paper comprising a plurality of holes for moving a test sample, wherein progesterone-BSA conjugate is immobilized on one end portion as a test line and anti-IgG is immobilized on the other end portion as a control line; and antiprogesterone IgG-gold conjugate for reacting with the test sample such as blood or milk. The inventive kit for diagnosing non-pregnancy can test the non-pregnancy of milch cow without any special device about 20 days after the artificial insemination. Furthermore, more accurate result can be obtained by using the kit since the nonpregnancy diagnosis is performed by comparing color of the test line with that of the control line. Excerpt(s): The present invention relates to a kit for diagnosing non-pregnancy and a method for diagnosing non-pregnancy of animal using the same, and more particularly, to a kit for diagnosing non-pregnancy and a method for early and easy diagnosis of nonpregnancy by detecting concentration of progesterone in blood, milk et al. of the animal. The estrous cycle of a normal milch cow is 19-22 days, and the progesterone concentration in blood or milk of the cow is almost 0 on estrous day. The progesterone concentration increases day by day from the estrous day, and generally decreases to below 1 ng/ml on 19th day after the estrous day if the cow is non-pregnant. On the other hand, if the milch cow is pregnant, the progesterone concentration does not decrease. Accordingly, non-pregnancy of milch cow can be examined by measuring progesterone concentration of crude milk or blood between 19th day and 22nd day after the estrous day. Before 1990s, pregnancy of milch cow was examined through a rectal examination by an expert when 50 or 60 days have passed after artificial insemination or mating. However, such a method generally requires a skilled veterinarian and causes quite a big economical loss because a long time is required to confirm the pregnancy of milch cow. In addition, if an ovary or an embryo is spurred during the rectal examination for the pregnancy diagnosis, there are possibility of ovarian disease or abortion, and the milch cow can get stressed. Further, according to the method mentioned above, the non-pregnancy can be doubtlessly diagnosed 50-60 days after the artificial insemination. If the milch cow is examined not to be pregnant at this moment, the process to catch the estrous sign of the non-pregnant animal and the artificial insemination should be repeated, which results in the big economical loss. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Lysosomal pepstatin-insensitive proteinase as a novel biomarker for detecting and diagnosing breast cancer Inventor(s): Pullarkat, Raju K; (Staten Island, NY), Junaid, Mohammed A; (Dayton, NJ) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 10154; US Patent Application Number: 20030211554 Date filed: March 27, 2003 Abstract: The present invention describes diagnostic and prognostic assays to detect in vascular and tissue samples the presence and activity of the lysosomal pepstatininsensitive proteinase, CLN2p, which has been newly found to be associated with breast cancer and serves as a novel biomarker for breast cancer, including primary, nonprimary, or metastatic breast tumors, neoplasms and carcinomas. The activity of CLN2p was discovered to be significantly elevated when measured in breast tissue samples from patients with primary breast carcinoma, compared with CLN2p levels in normal sample controls, thereby demonstrating an approximately two- to seventeen-fold higher CLN2p activity in breast tumors. These higher levels of CLN2p activity in breast tumors were positively correlated with several known breast cancer biomarkers, such as cathepsin D, estrogen receptor and progesterone receptor. The present invention thus provides CLN2p as new biomarker for use in the detection, diagnosis and prognosis of breast cancer. Excerpt(s): This application claims benefit of provisional patent application U.S. Serial No. 60/188,861, filed Mar. 13, 2000. The present invention relates to a biomarker newly found to be associated with breast carcinoma and a sensitive method for detecting and diagnosing breast cancer in patients. Lysosomal pepstatin-insensitive proteinase (CLN2p) is a novel mammalian enzyme discovered as a result of the identification of a gene defect in the fatal childhood neurodegenerative disorder, late-infantile neuronal ceroid lipofuscinosis (LINCL) (D. E. Sleat et al., 1997, "Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis", Science, 277:1802-1805). The gene encoding CLN2p is called CLN2. CLN2p is an abundant lysosomal proteinase with an optimum pH of 3.5 and is extremely stable in frozen tissues or in acidified homogenates (M. A. Junaid et al., 1999, "A novel assay for lysosomal pepstatin-insensitive proteinase and its application for the diagnosis of lateinfantile neuronal ceroid lipofuscinosis", Clin. Chim. Acta, 281:169-176). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Membrane associated progesterone receptor Inventor(s): Price, Thomas M.; (Greenville, SC) Correspondence: Dority & Manning; Attorneys AT Law, P.A.; Post Office Box 1449; Greenville; SC; 29602; US Patent Application Number: 20020197670 Date filed: June 22, 2001 Abstract: The invention provides for human progesterone receptor proteins (PR-M and PR-H) and polynucleotides that identify and encode the proteins. The invention also provides expression factor, host cells, and methods for treating and preventing disorders associated with the expression or binding of the PR-M and/or PR-H receptors.
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The invention also provides for antibodies, agonists, and antagonists that have utility in the treatment of similar disorders. Excerpt(s): This application is related to U.S. Application Serial No. 60/213,340, filed Jun. 22, 2000, and which is incorporated herein by reference. This invention is directed toward nucleic acid and amino acid sequences of novel human progesterone receptor complexes that are membrane bound and found within certain human tissues. The invention relates further to the use of the sequences and useful portions of sequences in the treatment, prevention, and diagnosis of various medical disorders. Progesterone has been recognized for years as the "pregnancy hormone" of mammals. The ovarian steroid plays a vital role by modulating the cellular processes that are necessary for the development and maintenance of reproductive function. Current studies with transgenic animals have revealed surprisingly that some of the reproductive functions attributed to estrogen are actually mediated by progesterone. Progesterone is now being touted as the "steroid hormone of reproduction". The effects of progesterone are mediated by unique receptors in reproductive tissues, identified as classical progesterone target tissues. Progesterone receptors (PR) have currently been identified in such nonclassical tissues as bone, prostate, and adipose tissue. The role of progesterone in these tissues has not been elucidated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and composition for improving fertility health in female and male animals and humans Inventor(s): Trant, Aileen Sontag; (Mountain View, CA) Correspondence: James C. Wray; Suite 300; 1493 Chain Bridge Road; Mclean; VA; 22101; US Patent Application Number: 20020122834 Date filed: December 22, 2000 Abstract: In a new pharmaceutical combination, the herb, Vitex agnus-castus (chasteberry), enhances hormone balance by increasing progesterone release and, therefore, ovulation frequency. The antioxidants, green tea, vitamin E, and selenium, improve overall reproductive health. L-arginine, an amino acid, stimulates the reproductive organs by improving circulation. Folic acid, vitamins B6 and B12, iron, zinc and magnesium help promote womens' fertility. Sperms are highly susceptible to free radical or oxidative damage from environmental toxicants and natural aging. Vitamins C and E, coenzyme Q10 and selenium are all potent antioxidants that help improve sperm counts and quality. Ferulic acid, an antioxidant found in Dong quai, also improves sperm quality. Zinc and B vitamins (B6, B12 and folate) are critical nutrients in male reproductive systems for hormone metabolism, sperm formation and motility. The amino acid, L-carnitine, promotes formation of healthy sperm. Excerpt(s): Because of delayed child bearing, unhealthy diets and use of tobacco, caffeine, alcohol, drugs and environmental contaminants, difficulties in conceiving have been experienced. Needs exist for pharmaceutical compounds that improve fertility in both women and men. This invention provides combinations of bioeffecting compounds for promoting fertility in men and women. The combinations include nutritional components that benefit fertility health. All the components have been studied separately, to determine their individual efficacy. The invention provides the first
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products to put these components together synergistically in women's and men's formulations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for reducing coronary artery reactivity Inventor(s): Hermsmeyer, R. Kent; (Portland, OR) Correspondence: Howard Eisenberg, ESQ.; Suite 1600; 601 SW Second Avenue; Portland; OR; 97204-3157; US Patent Application Number: 20030119799 Date filed: October 7, 2002 Abstract: A method for treating myocardial ischemia and angina pectoris comprising administering to a subject in need thereof an effective amount of progesterone with or without estrogen. Excerpt(s): This application is a continuation of pending U.S. patent application Ser. No. 09/548,476, filed on Apr. 13, 2000, which in turn is a continuation-in-part of U.S. patent application Ser. No. 08/806,358, filed Feb. 26, 1997 and entitled "Method for Reducing Coronary Artery Reactivity`. The entire disclosure of the above applications is incorporated herein by reference. The invention relates to the use of progesterone to reduce coronary artery reactivity, as well as kits relating thereto. The invention also involves screening methods and animal models for testing the ability of a compound to reduce coronary artery reactivity. Cardiovascular disease, including coronary heart disease, stroke and other vascular diseases, is the leading cause of death of men and women in economically-developed countries. The most common and lethal form of cardiovascular disease is ischemic heart disease. It has generally been regarded that ischemic heart disease is caused, primarily, by atherosclerosis of the coronary arteries. This is a condition where plaques form in the inner lining of the arteries, causing narrowing of the channel and thereby impairing blood flow to the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for the treatment of pain and other hormone-allergyrelated symptoms using dilute hormone solutions Inventor(s): Roby, Russell R.; (Austin, TX) Correspondence: Baker Botts L.L.P.; Patent Department; 98 San Jacinto BLVD., Suite 1500; Austin; TX; 78701-4039; US Patent Application Number: 20030096801 Date filed: November 14, 2002 Abstract: A method and composition for the treatment of hormone allergy is disclosed. The method relates to using progesterone dilutions, or any other steroid hormone, to treat the systemic symptoms of hormone allergy, including pain. The composition of the hormone dilutions ranges from 10.sup.-1 to 10.sup.-5. The hormone dilution may be administered sublingually, or, in the alternative, an intradermal route of administration may be chosen. Hormone dilutions may be administered at daily intervals or on any other treatment schedule as required to alleviate a patient's symptoms.
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Excerpt(s): This application claims the benefit, under 35 U.S.C.sctn. 119(e), of previously filed provisional application Methods And Compositions For The Treatment Of Allergy Using Dilute Hormone Solutions, Ser. No. 60/332,475, filed Nov. 16, 2001. The present invention relates in general to the treatment of pain and other hormone-allergy-related symptoms and in specific to the use of a dilute hormone solution for the treatment of pain and hormone-allergy symptoms. Hormone allergy has been previously described in the medical literature as premenstrual asthma. Skobeloff E. M., Spivey W. H., Silverman R. A., Ekin B. A., Harchelroad F. P., Alessi T. V.: The effect of the menstrual cycle on asthma presentations in the emergency department. Arch Intern Med 1996; 156: 1837-40. Claude F.: Asthma et menstruation. Presse Med 1938; 46: 755-759; Eliasson O., Scherzer H., DeGraff A. C.: Morbidity in asthma in relation to the menstrual cycle. J Allergy Clin Immunol 1986: 77: 87-94; Chandler M. H., Schuldheisz S., Phillips B., Muse K. N.: Pre-menstrual asthma: the effect of estrogen on symptoms, pulmonary function, and beta 2-receptors. Pharmacology 1997; 17(2): 224-234. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Modulators of antiestrogen pharmacology Inventor(s): Montano, Monica; (Shaker Heights, OH), Sutton, Amelia; (Cleveland Heights, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20020086361 Date filed: October 5, 2001 Abstract: A protein, designated ERCoA3 is provided. The ERCoA3 protein interacts with the estrogen receptor and the progesterone receptor and causes activation of these receptors is provided. Also provided are polynucleotides which encode ERCoA3 or block translation of the mRNA which encodes ERCoA3. Antibiodies that bind to one or more epitopes in the human ERCoA3 protein are provided. The present invention also relates to methods of inhibiting or reducing tamoxifen or estrogen induced proliferation of cancer cells, particularly breast cancer cells, endometrial cancer cells and uterine cancer cells. The method comprises reducing the activity or levels of ERCoA3 in such. Excerpt(s): This invention claims priority to U.S. Provisional Patent Application Serial No.: 60/238,190, filed Oct. 5, 2000. Estrogens are steroid hormones that are essential for normal sexual development and functioning of female reproductive organs. Estrogens are also important for growth, differentiation, and functioning of the testis, epididymis and prostate in males. Estrogens also have important non-reproductive effects on bones and the heart. Estrogens comprise a group of natural and synthetic substances. Natural estrogens include estradiol (i.e., 17-.beta.-estradiol or E2), estrone and estriol. Estrogens are sometimes given therapeutically in the form of a conjugate, such as for example, ethinyl estradiol, conjugated estrogens or diethylstilbestrol. Tissues in the body that are responsive to estrogens are called "estrogen-sensitive" or "estrogen-responsive" tissues and include cells of the urogenital tract, cardiovascular system and skeletal system. The cells that comprise estrogen-sensitive tissues contain estrogen receptors (ER). ER can be of the.alpha. type or.beta. type. Estrogens enter cells and bind to ER in the cytoplasm of such cells and an estrogen-ER complex is formed. Herein, a molecule such as estrogen that binds to a receptor is generally called a "ligand." Herein, a receptor such as ER that has formed a complex with a ligand is called a "liganded" receptor.
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Novel topical oestroprogestational compositions with a systemic effect Inventor(s): Gray, Georges; (Monoco, MC), Paris, Jacques `; (Nice, FR), Thomas, JeanLouis; (Charenton-Le-Pont, FR), Villet, Bertrand; (Antibes, FR) Correspondence: Muserlian And Lucas And Mercanti, Llp; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030181430 Date filed: June 26, 2002 Abstract: The present invention relates to the field of therapeutic chemistry and more especially to the realization of new galenic forms intended to be applied on the skin.More particularly it relates to a topical hormonal composition with a systemic effect for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of the ovarian hormonal deficiencies in women with amenorrhea, characterized in that it comprises, as active ingredients, a progestogen derived from 19nor progesterone and estradiol or one of its derivatives, a vehicle which allows the systemic passage of said active ingredients, chosen from the group constituted by a solubilizing agent, an absorption promoting agent, a film-forming agent, a gelling agent and their mixtures, in combination or in a mixture with suitable excipients for the realization of a gelled and/or film-forming pharmaceutical form. Excerpt(s): The present invention relates to the field of therapeutic chemistry and more especially to the realization of new galenic forms intended to be applied on the skin. A more particular subject of the present invention is cutaneous topical preparations the active ingredients of which are a synthetic progestogen and a natural or synthetic estrogen and the penetrating power of which makes it possible to obtain a systemic hormonal effect. The invention relates more specifically to a topical estrogenprogestogen composition with a systemic effect for the hormonal treatment of the perimenopause and of the menopause as well as for the treatment of ovarian hormonal deficiencies in women with amenorrhea. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel use of calreticulin in modulating hormone responsiveness and new pharmaceuticals for treating cancer, osteoporosis and chronic inflammatory disease Inventor(s): Dedhar, Shoukat; (Ontario, CA) Correspondence: T. Gene Dillahunty; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030060613 Date filed: November 29, 2001 Abstract: This invention relates to isolated and purified proteins, such as calreticulin and mimetics of calreticulin, for a novel use of modulating hormone responsiveness. These proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating a variety of diseases, including cancer, osteoporosis and chronic inflammatory disease. The proteins include or bind to an amino acid sequence KXFFYR, wherein X is either G, A or V and Y is either K or R. This sequence is present in the DNA-binding domain, and
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is critical for the DNA binding activity, of a variety of hormone receptors, including glucocorticoid receptor, minerolcorticoid receptor, androgen receptor, progesterone receptor, estrogen receptor, retinoic acid receptor, thyroid hormone receptor and vitamin D receptor. Proteins which bind to this sequence may inhibit hormone receptor induced gene transcription. Proteins which include this sequence may promote hormone receptor induced gene transcription. The invention includes isolated DNA molecules for these proteins, methods of treating diseases using these proteins, synthetic peptides and their mimetics, and kits containing these proteins, synthetic peptides or their mimetics. Excerpt(s): The physiology of many organs in mammals is regulated by hormones. These hormones include steroid hormones, thyroid hormones, metabolites of vitamins, such as all trans retinoic acid, 9-cis retinoic acid, vitamin D and its metabolite 1,25 dihydroxyvitamin D3. These hormones are proteins and bind to intracellular receptors which regulate expression of genes (O'Malley, 1990). There are a variety of receptors which respond to hormones. Osteoblasts and osteoclasts respond to steroid hormones, vitamin D and retinoic acid. Mammary epithelial cells and breast carcinoma cells respond to estrogens, progesterone, retinoic acid and glucocorticoids. Lymphocytes respond to glucocorticoids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for oxidation of steroids and genetically engineered cells used therein Inventor(s): Selten, Gerardus Cornelis Maria; (Berkel en Rodenrijs, NL), Slijkhuis, Herman; (Berkel en Rodenrijs, NL), Smaal, Eric Bastiaan; (Delft, NL) Correspondence: Charles A. Muserlian; C/o Bierman, Muserlian And Lucas; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030108982 Date filed: February 26, 2002 Abstract: An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting a of:the conversion of cholesterol to pregnenolone;the conversion of pregnenolone to progesterone;the conversion of progesterone to 17.alpha.-hydroxy-progesterone;the conversion of 17.alpha.-hydroxyprogesterone to cortexolone;the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 054,185 filed Apr. 26, 1993 which is a continuation of U.S. patent application Ser. No. 474,857 filed Oct. 30, 1990, now abandoned and of U.S. patent application Ser. No. 002,608 filed Jan. 11, 1993 which is a continuation of U.S. patent application Ser. No. 474,798 filed Jul. 16, 1990, now abandoned.DELTA.sup.4-pregnene-11.beta., 17.alpha., 21-triol-3, 20-dione (hydrocortisone) is an important pharmaceutical steroid, used for its pharmacological properties as a corticosteroid and as a starting compound for the preparation of numerous useful steroids, particularly other corticosteriods. Hydrocortisone is produced in the adrenal cortex of vertebrates and was originally obtained, in small amounts only, by a laborious extraction from adrenal cortex tissue. Only after structure elucidation were new production routes developed, characterized
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by a combination of chemical synthesis steps and microbiological conversions. Only because the starting compounds which are employed such as sterols, bile acids and sapogenins are abundant and cheap, the present processes afford a less expensive product, but these still are rather complicated. Several possibilities were envisaged to improve the present processes, and also biochemical approaches have been tried. One attempt was to have a suitable starting steroid converted in an in vitro biochemical system using the isolated adrenal cortex proteins which are known to be responsible for the enzymatical conversion in vivo of steroids to hydrocortisone. However, the difficult isolation of the proteins and the high price of the necessary cofactors, appeared to be prohibitive for an economically attractive large scale process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for preparing17alpha-acetoxy-11beta-[4-n,n(dimethylamino)phenyl]-2- 1methoxy-19-norpregna-4,9-diene -3,20-dione, intermediates useful in the process , and processes for preparing such intermediates Inventor(s): Cessac, James W; (San Antonio, TX), Kim, Hyun Koo; (Bethesda, MD), Rao, Pemmaraju N; (San Antonio, TX), Simmons, Anne Marie; (San Antonio, TX) Correspondence: Leydig Voit & Mayer, Ltd; 700 Thirteenth ST. NW; Suite 300; Washington; DC; 20005-3960; US Patent Application Number: 20030060646 Date filed: June 27, 2002 Abstract: A compound having general formula (I) in which R.sup.1 is a member selected from the group consisting of --OCH.sub.3, --SCH.sub.3, --N(CH.sub.3).sub.2, -NHCH.sub.3, --CHO, --COCH.sub.3 and --CHOHCH.sub.3; R.sup.2 is a member selected from the group consisting of halogen, alkyl, acyl, hydroxy, alkoxy, acyloxy, alkyl carbonate, cypionyloxy, S-alkyl and S-acyl; R.sup.3 is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R.sup.4 is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of --O and --N--OR.sup.5, wherein R.sup.5 is a member selected from the group consisting of hydrogen and alkyl. In addition to providing the compounds of formula (I), the present invention provides methods wherein the compounds of formula (I) are advantageously used, inter alia. to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce labor; and for contraception. 1 Excerpt(s): This application claims the benefit of U.S. provisional patent application No. 60/173,470, filed Dec. 29, 1999, the disclosure of which is incorporated by reference in its entirety. The present invention relates generally to steroids, and in particular to a process for preparing 17.alpha.-acetoxy-11.beta.-[4-N,N-(- dimethylamino)phenyl]-21methoxy-19-norpregna-4,9-diene-3,20-dione, intermediates useful in the process, and processes for preparing such intermediates. International patent application No. PCT/US 97/07373, filed Apr. 30, 1997, WO 97/41145, published Nov. 6, 1997, and U.S. provisional patent application No. 60/016,628, filed May 1, 1996, both assigned to the same assignee as the present application, disclose, inter alia, 17.alpha.-acetoxy-11.beta.[4-N,N-(dimethylamino)phenyl]-21-methoxy-19-no- rpregna-4,9-diene-3,20-dione as an antiprogestational agent. This compound also is useful in other treatments, e.g., to induce menses or labor, to treat diseases such as endometriosis, dysmenorrhea, and
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endocrine hormone-dependent tumors, uterine fibroids, and to inhibit uterine endometrial proliferation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Progesterone receptor complex p23-like protein Inventor(s): Kaser, Matthew R.; (Castro Valley, CA), Yue, Henry; (Sunnyvale, CA) Correspondence: Legal Department; Incyte Genomics, INC.; 3160 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20020132238 Date filed: May 29, 2001 Abstract: The invention provides progesterone receptor complex p23-like protein and its encoding cDNA. It also provides for the use of the cDNA, protein, and antibodies in the diagnosis, prognosis, treatment and evaluation of therapies for neoplastic disorders and immune response. The invention further provides vectors and host cells for the production of the protein and transgenic model systems. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/325,993, filed Jun. 4, 1999, and U.S. Pat. No. 5,952,175, issued Sep. 14, 1999. This invention relates to a human progesterone receptor complex p23-like protein and its encoding cDNA and to the use of these biomolecules in the diagnosis, prognosis, treatment and evaluation of therapies for neoplastic disorders and immune response. Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of molecules, biochemical and physiological mechanisms, and metabolic pathways. Despite different evolutionary pressures, the proteins of nematode, fly, rat, and man have common chemical and structural features and generally perform the same cellular function. Comparisons of the nucleic acid and protein sequences from organisms where structure and/or function are known accelerate the investigation of human sequences and allow the development of model systems for testing diagnostic and therapeutic agents for human conditions, diseases, and disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Progesterone receptor-regulated gene expression and methods related thereto Inventor(s): Horwitz, Kathryn B.; (Greenwood Village, CO), Richer, Jennifer; (Denver, CO) Correspondence: Angela Dallas-pedretti; Sheridan Ross P.C.; Suite 1200; 1560 Broadway; Denver; CO; 80202-5141; US Patent Application Number: 20030027208 Date filed: March 21, 2001 Abstract: Disclosed are expression profiles of genes that are regulated by progesterone receptors, and particularly by progesterone receptor isoforms PR-A and PR-B. Methods for using such genes to identifying progesterone receptor agonist and antagonist ligands are described. Also described are methods for identifying isoform-specific progesterone receptor ligands, for identifying tissue-specific progesterone receptor ligands, and for determining the profile of genes regulated by progesterone receptors in
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a breast tumor sample. In addition, pluralities of polynucleotides from genes that are regulated by progesterone receptors are disclosed, as are pluralities of antibodies that selectively bind to proteins encoded by such genes. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn. 119(e) from U.S. Provisional Application Serial No. 60/214,870, filed Jun. 28,2000, entitled "Surrogate Gene Markers for Two Different Progesterone Receptor Isoforms in Breast Cancer, and Their Use to Screen for Isoform-Selective Progestational Ligands". The entire disclosure of U.S. Provisional Application Serial No. 60/214,780 is incorporated herein by reference. This invention generally relates to expression profiles of genes that are regulated by progesterone receptors, and particularly by progesterone receptor isoforms PR-A and PR-B, and to the use of such genes in methods for identifying progesterone receptor agonist and antagonist ligands, including progesterone receptor isoform-specific ligands and tissue-specific ligands. This invention also relates to methods for determining the profile of genes regulated by progesterone receptors in a tissue sample. In addition, pluralities of polynucleotides transcribed from genes that are regulated by progesterone receptors are disclosed, as are pluralities of antibodies that selectively bind to proteins encoded by such genes. Progesterone is a natural reproductive hormone that targets the breast, uterus, ovaries, brain, bone, blood vessels, immune system, etc. Progestational agents are widely used for oral contraception, menopausal hormone replacement therapy, and cancer treatments. Antiprogestins, which are synthetic ligands that antagonize the actions of progesterone, are in clinical trials for contraception, for induction of labor, and to treat endometriosis, breast cancers and meningiomas. The actions of progesterone are varied and tissue-specific. Even in the normal breast it can have diverse effects: depending on the physiological state of the woman, progesterone can be proliferative, antiproliferative, or differentiative. Additionally, progesterone promotes the development of breast cancers and accelerates the growth of established breast cancers. For example, when used for hormone replacement therapy at menopause, progestins, which are synthetic progestational agents, increase the risk of breast cancer. Paradoxically, they are protective in the uterus and prevent endometrial cancers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Ratite oil as a topical adjuvant and transdermal carrier Inventor(s): Wells, Linda; (Northridge, CA) Correspondence: Linda Wells; 9013 Amigo AVE.; Northridge; CA; 91324; US Patent Application Number: 20030091650 Date filed: November 13, 2001 Abstract: My invention is the use of ratite oil as a topical adjuvant and as a transdermal delivery vehicle to carry agents, especially medicines, into the bodies of mammals, including humans. This patent application specifically excludes progesterone as one of the claimed agents (U.S. Pat. No. 6,303,132), and the topical use of plain emu oil (patent application 20010033838). Excerpt(s): No federal funds were used by the inventor in the creation of this invention. It all started with my father, an intelligent and curious engineer who loves to tour factories, ranches, nature preserves; family outings are invariably educational. During a week long visit, I took him to Mourning Cloak Botanical Gardens for a tour. To my horror, I heard one of the staff recommending DMSO as a carrier for some of their
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alternative medicinal plant preparations. Although efficacious, DMSO has toxic side effects, and is not recommended for human use. The next day we were touring ostrich, emu, and rhea ranches, when I overheard a ranch hand complain about how ostrich oil went right through his gloves, which my quick glance revealed were heavy leather. As a research scientist, I am very sensitive to proper glove usage for different toxins for adequate skin protection, as my life depends upon a successful choice of material. It occurred to me immediately that if this oil could easily penetrate old, thick leather, it should effectively penetrate human skin, and could act as a transdermal carrier. Further, ostrich oil is nontoxic, unlike DMSO, so I was hopeful that it could be utilized as a safe and efficacious carrier for medicinal compounds, both alternative and traditional. To test this idea, I decided to make a cream with ostrich fat and herbal anti-inflammatories to treat the carpal tunnel in my wrists. I have suffered from pain in my wrists from some years, and was diagnosed by a Kaiser physician with carpal tunnel. First I purchased some ostrich fat from a processing plant and rendered the oil from the fat in my crockpot. I mixed it with other ingredients to make a nice cream, then added comfrey root tincture, thyme, and turmeric as active ingredients, which are herbal medicines reputed to reduce inflammation. I applied the cream to the inside of my wrists three times daily. During the next few weeks, my pain slowly but steadily decreased, until after six weeks I was free of pain. The carpal tunnel syndrome does recur with overuse of my hands or extended vibration, but the cream works quite well for reduction of the pain and symptoms. It is certainly preferably to the only other option - surgery. For commercial applications, I would definitely omit the turmeric, as it stains everything it contacts a brilliant yellow. I also gave some of the cream to an woman whose elderly husband was in constant pain from arthritis. I explained how to test for an allergic reaction before use, then told her to apply the cream three times/day on the painful joints. She reported that he did experience some relief from pain, although there was not a complete cure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Screening, diagnostic and therapeutic methods relating to RIZ Inventor(s): Huang, Shi; (San Diego, CA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20030092095 Date filed: May 9, 2002 Abstract: The invention provides a method of screening for a compound that modulates RIZ histone methyltransferase (HMT) activity, by contacting a RIZ or RIZ fragment having HMT activity with one or more candidate compounds, and determining histone methyltransferase activity of the contacted RIZ or RIZ fragment. Also provided is a method of screening for a compound that modulates progesterone receptor (PR) activity, by providing a RIZ1 modulatory compound, and determining the ability of the RIZ1 modulatory compound to modulate PR activity. Further provided is a method of identifying an individual with an estrogen receptor positive (ER+) tumor having a reduced likelihood of responding to endocrine therapy. The method involves determining the RIZ1 status of the tumor, wherein an abnormal RIZ1 status identifies the individual as an individual with a reduced likelihood of responding to endocrine therapy.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/290,481, filed May 11, 2001, which is incorporated herein by reference in its entirety. This invention relates generally to the fields of cancer biology and endocrinology and, more specifically, to biological activities of RIZ polypeptides. Post-translational addition of methyl groups to the amino-terminal tails of histone proteins is catalyzed by a family of proteins known as histone methyltransferases (HMTs). Histone site-specific methylation is associated with a variety of fundamental cellular processes, including transcriptional regulation, epigenetic silencing and heterochromatin formation. Loss of HMT function is expected to directly contribute to the de-differentiation and genomic instability that are characteristic of cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted 2-arylimino heterocycles and compositions containing them for use as progesterone receptor binding agents Inventor(s): Bagi, Cedo M.; (Branford, CT), Brennan, Catherine R.; (Milford, CT), Brittelli, David R.; (Branford, CT), Bullock, William H.; (Easton, CT), Chen, Jinshan; (Hamden, CT), Collibee, William L.; (Bethany, CT), Dally, Robert; (East Haven, CT), Dixon, Brian R.; (Woodbridge, CT), Johnson, Jeffrey S.; (Branford, CT), Kluender, Harold C. E.; (Trumbull, CT), Lathrop, William F.; (Plantsville, CT), Liu, Peiying; (Madison, CT), Mase, Carol Ann; (Ringoes, NJ), Redman, Aniko M.; (Derby, CT), Scott, William J.; (Guilford, CT), Urbahns, Klaus; (Wuppertal, DE), Wolanin, Donald J.; (Orange, CT) Correspondence: Jeffrey M. Greenman; Vice President, Patents And Licensing; Bayer Corporation; 400 Morgan Lane; West Haven; CT; 06516; US Patent Application Number: 20030207865 Date filed: October 23, 2001 Abstract: This invention relates to 2-arylimino heterocycles, including 2-arylimino-1,3thiazolidines, 2-arylimino-2,3,4,5-tetrahydro-1,3-thiazin- es, 2-arylimino-1,3-thiazolidin4-ones, 2-arylimino-1,3-thiazolidin-5-ones- , and 2-arylimino-1,3-oxazolidines, and their use in modulating progesterone receptor mediated processes, and pharmaceutical compositions for use in such therapies. Excerpt(s): This invention relates to heterocyclic pharnaceuticals, and more particularly, to 2-arylimino heterocycles, pharmaceutical compositions containing them, and their use in modulating progesterone receptor mediated processes. H1) for the promotion of mylin repair (Baulieu et al., Cell. Mol. Neurobiol., 16, 143 (1996); Baulieu et al., Mult. Scler., 3, 105 (1997); Schumaker et al., Dev. Neurosci., 18, 6 (1996); Koenig et al., Science, 268, 1500 (1995)). Currently, progesterone or progestins alone or in combination with estrogens are clinically indicated: for contraception (Merck Manual; Merck & Co. (1992)); for treatment of gastrointestional bleeding due to arteriovenous malformations (Merck Manual; Merck & Co. (1992)); for treatment of recurrent metatarsal stress fractures complicated by oligiomenorrhea or amenorrhea (Merck Manual; Merck & Co. (1992)); for treatment of premenstral syndrome (PMS, premenstral tension; Merck Manual; Merck & Co. (1992)); for postmenopausal hormone replacement therapy (Merck Manual; Merck & Co. (1992)); for treatment of hot flashes and subsequent insomnia and fatigue during menopause (Merck Manual; Merck & Co. (1992)); for treatment of dysfunctional uterine bleeding when pregnancy is not desired (Merck Manual; Merck & Co. (1992)); and for suppression of endometriosis (Merck Manual; Merck & Co. (1992)), breast cancer (Merck Manual; Merck & Co. (1992)), endometrial cancer (Merck Manual; Merck & Co. (1992)), or luteal insufficiency (Merck Manual; Merck & Co. (1992)). For
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example, medroxyprogesterone, a progestin, alone or in combination with estrogens is indicated for prevention of osteoporosis, treatment of vulvar and/or vaginal atrophy, treatment of moderate to severe vasomotor symptoms associated with menopause, treatment of secondary amenorrehea, treatment of abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, prevention of pregnancy, or as adjunctive therapy and palliative treatment of inoperable, recurrent, and metastatic endometrial or renal carcinoma (Merck Manual; Merck & Co. (1998)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
System for optimising the production performance of a milk producing animal herd Inventor(s): Chen, Fei; (Lynge, DK), Hansen, Henrik; (Farum, DK), Larsen, Flemming; (Haarby, DK), Mathiasen, Thomas; (Kobenhavn O, DK) Correspondence: Hunton & Williams; Intellectual Property Department; 1900 K Street, N.W.; Suite 1200; Washington; DC; 20006-1109; US Patent Application Number: 20020124803 Date filed: March 7, 2002 Abstract: A system for optimizing the production performance of a milk producing animal herd is provided. The system comprises milk sampling means, analytical means comprising separate means for analyzing compounds or parameters that in the presence of compounds indicative of the physiological or nutritional condition of the herd member, generates detectable signals, and means for directing a part of the milk sample to each separate analyzing means which is controlled by data for the physiological and nutritional state of a herd member such that the directing means is only activated at preselected points in time or at pre-selected time intervals in the production and or lactation cycles. Specific compounds are compounds indicative of mastitis, including beta-N-acetylhexosaminidase (NAGase) E.C. 3.2.1.52 and lactate dehydrogenase (LDH), protein balance, including milk urea nitrogen (MUN) and total protein, ketosis, including acetolactate, beta-hydroxybutyrate, acetone and lipids, fat and state in reproduction cycle, including a steroid or peptide hormone such as progesterone. Furthermore, the system comprises signal detection means for recording and processing the signals, means for data storage and data output means. Additionally there are provided methods for optimizing the production performance of a milk producing animal herd and an apparatus herefor. Excerpt(s): The present invention relates generally to a system and methods for optimising the production performance of a milk producing animal herd. More specifically, it provides automated or semi-automated means for dynamic real time analyses of milk compounds and parameters to provide quantitative analytical data that are indicative of the overall physiological and nutritional state of the milking animals and which, if required, permit appropriate corrective measures to be taken. It is known to monitor the physiological and nutritional condition of milking animals, such as cows. It is also known to collect data from individual milking animals, including data for milk yield and composition, health condition data, feeding scheme data and breeding data such as genetic data. A currently common procedure is to collect milk samples manually from individual milking animals at regular intervals and subsequently ship the samples to a central laboratory for chemical and biological analyses, thereby deriving information on the milk quality as well as the health condition of each individual milking animal. In most milk producing countries, dairy herd improvement associations (DHIAs) will collect, evaluate and distribute such data relating to e.g. milk yield, milk
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quality and mastitis (i.e. inflammation of the mammary gland). Based on these data that are available from the DHIAs, the dairy farmers can select the best milking animals for breeding, make appropriate adjustments to feeding schemes and control health to thereby optimise the milk production. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Topical testosterone formulations and associated methods Inventor(s): Kryger, Abraham H.; (Monterey, CA) Correspondence: Thorpe North Western; 8180 South 700 East, Suite 200; P.O. Box 1219; Sandy; UT; 84070; US Patent Application Number: 20020150625 Date filed: December 11, 2001 Abstract: A topical testosterone formulation is disclosed. In one aspect, the formulation may include a therapeutically effective amount of micronized testosterone, an arginine ingredient, and a tocopherol ingredient admixed with a poloxamer lecithin organogel. Additional ingredients may be included, such as melatonin, oxytocin, DHEA, and progesterone. Excerpt(s): This application claims priority to United States Provisional Patent Application Serial No. 60/254,713, filed on Dec. 11, 2000, which is hereby incorporated by reference. The present invention relates to topical testosterone formulations, including methods for making and using such formulations. Accordingly, this invention covers the fields of pharmaceutical sciences and medicine. Hormone replacement therapy has been used in the past to treat patients who have lost the ability to make the hormones or who have reduced hormone levels. Further, testosterone replacement therapy has been used to treat patients with abnormally low testosterone levels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of antigestagens for inhibiting accelerated endometrial maturation during infertility treatment Inventor(s): Beier, Henning M.; (Aachen, DE), Hegele-Hartung, Christa; (Muelheim a.d Ruhr, DE), Hess-Stumpp, Holger; (Berlin, DE), Krusche, Claudia; (Aachen, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020143000 Date filed: March 9, 2001 Abstract: A method of inhibiting the occurrence of advanced endometrium maturation in a female mammal undergoing fertility treatment is disclosed. The method comprises the administration at least one 17.alpha.-fluoralkylated progesterone receptor antagonist to the female mammal. Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/756,286 filed Jan. 9, 2001, which is incorporated by reference herein in its entirety. This invention relates to the use of antigestagens for shifting post-ovulatory endometrial maturation during infertility treatment. Ovarian stimulation with gonadotropins is commonly used in
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humans in assisted reproductive technologies, including in vitro fertilization and embryo transfer therapy (IVF/ET). However, the post-ovulatory endometrial transformation is advanced after controlled ovarian hyperstimulation (Garcia et al., 1984, Fertil. Steril. 41:31-37; Paulson et al., 1997, Fertil. Steril. 76:321-325; Kolb, 1997, Fertil. Steril. 67:625-630; Franchin et al., 1999, Fertil. Steril. 71:174-181.) As a consequence, the usual precisely synchronized temporal development of the endometrium and the embryo is disrupted, resulting in low implantation rates for healthy blastocysts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with progesterone, 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 “progesterone” (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 progesterone. You can also use this procedure to view pending patent applications concerning progesterone. 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 7. BOOKS ON PROGESTERONE Overview This chapter provides bibliographic book references relating to progesterone. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on progesterone include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “progesterone” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “progesterone” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “progesterone” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Action of Progesterone on the Brain; ISBN: 3540134336; http://www.amazon.com/exec/obidos/ASIN/3540134336/icongroupinterna
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Action of Progesterone on the Brain (Current Topics in Neuroendocrinology, Vol 5) by D. Ganten (Editor) (1985); ISBN: 0387134336; http://www.amazon.com/exec/obidos/ASIN/0387134336/icongroupinterna
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Biochemical actions of progesterone and progestins; ISBN: 0890720320; http://www.amazon.com/exec/obidos/ASIN/0890720320/icongroupinterna
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Hormone Replacement Therapy Yes or No?: How to Make an Informed Decision About Estrogen, Progesterone, & Other Strategies for Dealing With Pms, Menopause, & Osteoporosis by Betty Kamen (1996); ISBN: 0944501109; http://www.amazon.com/exec/obidos/ASIN/0944501109/icongroupinterna
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Immunosuppression by Progesterone in Pregnancy by Julia Szekeres-Bartho, Julia Szekeres; ISBN: 0849353963; http://www.amazon.com/exec/obidos/ASIN/0849353963/icongroupinterna
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Natural Progesterone Cream by C. Norman Shealy; ISBN: 0879838892; http://www.amazon.com/exec/obidos/ASIN/0879838892/icongroupinterna
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Natural Progesterone the Multiple Roles by John R Lee (Author); ISBN: 0964373718; http://www.amazon.com/exec/obidos/ASIN/0964373718/icongroupinterna
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Natural Progesterone: The Multiple Roles of a Remarkable Hormone by John Lee (1999); ISBN: 1897766548; http://www.amazon.com/exec/obidos/ASIN/1897766548/icongroupinterna
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Natural Progesterone: The Natural Way to Alleviate Symptoms of Menopause, Pms, Endometriosis and Other Hormone-Related Problems by Anna Rushton, Shirley A. Bond (2003); ISBN: 000715609X; http://www.amazon.com/exec/obidos/ASIN/000715609X/icongroupinterna
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Pharmacology of the Endocrine System and Related Drugs: Progesterone, Progestational Drugs and Antifertility Agents by Lars Philip Bengtsson (1971); ISBN: 0080157459; http://www.amazon.com/exec/obidos/ASIN/0080157459/icongroupinterna
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Premenstrual Syndrome and Progesterone Therapy by Katharina Dalton; ISBN: 0815122667; http://www.amazon.com/exec/obidos/ASIN/0815122667/icongroupinterna
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Progesterone and progestins; ISBN: 0890047693; http://www.amazon.com/exec/obidos/ASIN/0890047693/icongroupinterna
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Progesterone function: molecular and biochemical aspects; ISBN: 0842270450; http://www.amazon.com/exec/obidos/ASIN/0842270450/icongroupinterna
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Progesterone in Hormone Replacement Therapy by R.A. Lobo, F. Naftolin; ISBN: 1850704406; http://www.amazon.com/exec/obidos/ASIN/1850704406/icongroupinterna
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Progesterone Induces Apoptosis in Eosinophilic Granulocytes & Induces Tumour Necrosis Factor-Alpha / Tumour Necrosis Factor Receptor (Acta Biomedica Lovaniensia, 256) by Joeri Aerts (2002); ISBN: 9058672166; http://www.amazon.com/exec/obidos/ASIN/9058672166/icongroupinterna
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Progesterone receptors in normal and neoplastic tissues; ISBN: 0890041636; http://www.amazon.com/exec/obidos/ASIN/0890041636/icongroupinterna
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Progesterone: its regulatory effect on the myometrium: Ciba Foundation Study Group No. 34; in memory of Brenda M. Schofield; ISBN: 0700014446; http://www.amazon.com/exec/obidos/ASIN/0700014446/icongroupinterna
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The Certification of Progesterone in 2 Lyophilized Serum Materials CRM 347 and CRM 348 by L.M.R. Thienpont; ISBN: 0119722712; http://www.amazon.com/exec/obidos/ASIN/0119722712/icongroupinterna
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The Estrogen Alternative: Natural Hormone Therapy with Botanical Progesterone by Raquel Martin, Judi Gerstung (Contributor); ISBN: 089281893X; http://www.amazon.com/exec/obidos/ASIN/089281893X/icongroupinterna
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The ferret : some observations on photoperiod and gonadal activity, and their role in seasonal pelt and bodyweight changes : the synergistic effect of oestrogen and
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progesterone on weight gain : and a comparative study of the corpus luteum of the ferret and the rabbit by John Hammond; ISBN: 0950340006; http://www.amazon.com/exec/obidos/ASIN/0950340006/icongroupinterna •
Wild Yam: Nature's Progesterone: The Safe and Little Known Answer to Hormonal Imbalance, Pms, Menopause and Osteoporosis (Woodland Health Ser) by Rita Elkins, Woodland Publishing (1999); ISBN: 1885670257; http://www.amazon.com/exec/obidos/ASIN/1885670257/icongroupinterna
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Women, Your Body & Natural Progesterone by Francisco Dr. Contreras, et al; ISBN: 1579460046; http://www.amazon.com/exec/obidos/ASIN/1579460046/icongroupinterna
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Your Hormoneous Life - Learn the Secrets of Progesterone by Calvin, D.C., B.E.C.O. Ross; ISBN: 1887314229; http://www.amazon.com/exec/obidos/ASIN/1887314229/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “progesterone” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Brook Lodge symposium: progesterone. Author: Barnes, Allan C. (Allan Campbell),; Year: 1967; Augusta, Mich., Brook Lodge Press [1961]
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Effects of oestrone and progesterone on mammary glands of thyroidectomized gonadectomized rabbits, by H. Liedholm and A. Norgren. Author: Liedholm, Hans.; Year: 1967; Lund, Gleerup, 1967
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In vitro-metabolism of 3H-progesterone in human testicular tissue Author: Berg, A. Aason.; Year: 1979; Copenhagen: [s.n.], 1976; ISBN: 8774941445
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Mammary development in alloxan diabetic rabbits injected with oestrone and progesterone. Author: Norgren, A. (Allan); Year: 1967; Lund, Gleerup, 1967
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Progesterone and the defence mechanism of pregnancy; in honour of Dr. G. W. Corner. Editors for the Ciba Foundation: G. E. W. Wolstenholme and Margaret P. Cameron. Author: Ciba Foundation.; Year: 1961; Boston, Little, Brown [1961]
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Progesterone therapy of the inadequate luteal phase Author: Wentz, Anne Colston,; Year: 1976; Chicago: Year Book Medical Publishers, c1982; ISBN: 0815199252 http://www.amazon.com/exec/obidos/ASIN/0815199252/icongroupinterna
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Progesterone; its regulatory effect on the myometrium. In memory of Brenda M. Schofield. Edited by G. E. W. Wolstenholme and Julie Knight. Author: Knight, Julie.; Year: 1969; London, Churchill, 1969; ISBN: 700014446
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Progesterone-dependent sexual behavior and protein patterns in the ventromedial hypothalamus of the adult female rat [microform] Author: Montemayor, Michelle E.; Year: 1964; [Argonne, Ill.?: Argonne National Laboratory?, 1994?]
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Studies on masking of chromatin acceptor sites for the avian progesterone receptor Author: Dani, Ginger Martin.; Year: 1983; [Minneapolis?: s.n.], 1981
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The premenstrual syndrome and progesterone therapy Author: Dalton, Katharina,; Year: 1978; London: Heinemann Medical Books; Chicago: Year Book Medical Publishers, 1977; ISBN: 0815122659 http://www.amazon.com/exec/obidos/ASIN/0815122659/icongroupinterna
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Uterine progesterone and progesterone binding proteins Author: Haukkamaa, Maija.; Year: 1982; Helsinki: [s.n.], 1975; ISBN: 9519906851
Chapters on Progesterone In order to find chapters that specifically relate to progesterone, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and progesterone using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “progesterone” (or synonyms) into the “For these words:” box.
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CHAPTER 8. PERIODICALS AND NEWS ON PROGESTERONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover progesterone.
News Services and Press Releases One of the simplest ways of tracking press releases on progesterone 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 “progesterone” (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 progesterone. 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 “progesterone” (or synonyms). The following was recently listed in this archive for progesterone: •
Progesterone antagonist may slow Charcot-Marie-Tooth disease Source: Reuters Industry Breifing Date: November 13, 2003
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Mutated progesterone receptor may explain idiopathic infertility Source: Reuters Medical News Date: September 26, 2003
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Progesterone metabolite reduces risk of preterm delivery in high-risk women Source: Reuters Medical News Date: June 11, 2003
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Prophylactic vaginal progesterone reduces rate of preterm delivery Source: Reuters Medical News Date: March 17, 2003
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Progesterone-based drug prevents preterm birth Source: Reuters Health eLine Date: February 07, 2003
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Weekly progesterone injections reduce risk of recurrent preterm births Source: Reuters Medical News Date: February 06, 2003
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Progesterone receptor in breast tumor more prognostic than estrogen receptor Source: Reuters Medical News Date: August 13, 2002
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Serono settles with Columbia Labs in Crinone recall Source: Reuters Industry Breifing Date: June 05, 2002
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Serono reintroduces Crinone gel in US Source: Reuters Industry Breifing Date: March 12, 2002
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Serono not ready to relaunch Crinone vaginal gel Source: Reuters Industry Breifing Date: November 28, 2001
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Progesterones don't cure PMS, research shows Source: Reuters Health eLine Date: October 05, 2001
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Progesterone is ineffective for premenstrual syndrome Source: Reuters Industry Breifing Date: October 04, 2001
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Columbia expects Crinone to be ready for re-shipment in mid-October Source: Reuters Industry Breifing Date: September 21, 2001
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Premenstrual drop in progesterone appears to explain perimenstrual asthma Source: Reuters Medical News Date: May 25, 2001
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Watson to face competition selling progesterone in sesame oil Source: Reuters Industry Breifing Date: May 07, 2001
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APP wins FDA nod for generic progesterone based on Gensia drug Source: Reuters Industry Breifing Date: April 26, 2001
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “progesterone” (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 “progesterone” (or synonyms). If you know the name of a company that is relevant to progesterone, 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 “progesterone” (or synonyms).
Academic Periodicals covering Progesterone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to progesterone. In addition to
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these sources, you can search for articles covering progesterone that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. 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 progesterone. 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 progesterone. 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 progesterone: Conjugated Estrogens and Medroxyprogesterone for Ovarian Hormone Therapy (Oht) •
Systemic - U.S. Brands: Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/209441.html
Medroxyprogesterone and Estradiol •
Systemic - U.S. Brands: Lunelle http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500255.html
Menotropins •
Systemic - U.S. Brands: Humegon; Pergonal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202347.html
Progesterone Intrauterine Device •
Iud) - U.S. Brands: Progestasert http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202774.html
Progestins for Contraceptive Use •
Systemic - U.S. Brands: Depo-Provera Contraceptive Injection; Micronor; NORPLANT System; Nor-QD; Ovrette; Plan B http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202757.html
Progestins for Noncontraceptive Use •
Systemic - U.S. Brands: Amen; Aygestin; Crinone; Curretab; Cycrin; DepoProvera; Gesterol 50; Gesterol LA 250; Hy/Gestrone; Hylutin; Megace; Prodrox; Prometrium; Pro-Span; Provera http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202758.html
Urofollitropin •
Systemic - U.S. Brands: Fertinex; Metrodin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202586.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/.
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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
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
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
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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/
12
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/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
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
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
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.13 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:14 •
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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
13
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). 14 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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “progesterone” (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 72109 1513 287 48 0 73957
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “progesterone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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 Biologists20 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.21 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.22 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/.
The Genome Project and Progesterone In the following section, we will discuss databases and references which relate to the Genome Project and progesterone. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21
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. 22 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. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “progesterone” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for progesterone: •
Progesterone Receptor Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607311
•
Progesterone Receptor Membrane Component 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300435
•
Progesterone Receptor Membrane Component 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607735
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Progesterone Resistance Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?264080
•
Progesterone-induced Blocking Factor 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607532
•
Unactive Progesterone Receptor, 23-kd Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607061 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
•
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
•
Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
•
NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
•
Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
•
OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
•
PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
•
ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
•
PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
•
Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
•
Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “progesterone” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis.
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “progesterone” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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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 progesterone 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 progesterone. 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 progesterone. 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 “progesterone”:
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•
Other guides High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Menstruation and Premenstrual Syndrome http://www.nlm.nih.gov/medlineplus/menstruationandpremenstrualsyndrome.ht l Pregnancy Loss http://www.nlm.nih.gov/medlineplus/pregnancyloss.html Uterine Diseases http://www.nlm.nih.gov/medlineplus/uterinediseases.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on progesterone. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Repeated Miscarriage Source: Washington, DC: American College of Obstetricians and Gynecologists. 2000. 6 p. Contact: Available from American College of Obstetricians and Gynecologists, Distribution Center, P.O. Box 4500, Kearneysville, WV 25430-4500. (800) 762-2264, ext. 931 (orders), (304) 725-8410, ext. 339 (orders), (800) 525-5562 (Fax),
[email protected] (Email), http://www.acog.org (Web Site). $17.50 for a package of 50 brochures. Order No. AP100. Summary: Miscarriage is the loss of a pregnancy before 20 weeks' gestation. This pamphlet focuses on repeated miscarriage, which is defined as three or more miscarriages in a row. Miscarriage occurs in about 15 to 20 percent of all pregnancies, usually during the first 3 months. Often the reason for repeated miscarriage is not known, but one major cause is problems with the chromosomes of the fetus. Most
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chromosomal problems occur by chance, and are not likely to occur again in a later pregnancy. However, in a small number of cases, problems with the parents' chromosomes can cause repeated miscarriage. There are tests to find out if chromosomal problems are a factor in repeated miscarriage. Another cause of repeated miscarriage is illness in the mother. Illnesses that have been linked to repeated miscarriage include systemic lupus erythematosus and other autoimmune disorders, congenital heart disease, severe kidney disease, diabetes that is uncontrolled, thyroid disease, and intrauterine infection. Other causes include lack of progesterone (this is needed to fertilize the egg); disorders of the immune system; abnormalities of the uterus; and environmental and lifestyle factors such as smoking, drinking alcohol, using illegal drugs, and being exposed to high levels of radiation or toxic agents. Since repeated miscarriage has many possible causes, one's doctor will need to gather a lot of information to diagnose the problem. He or she will need to do a complete medical history and a complete physical exam. Other tests that may be done include blood analysis, chromosomal testing of both parents, genital tract cultures, chromosomal testing of fetal tissue, endometrial biopsy, hysterosalpingography, hysteroscopy, laparoscopy, and ultrasound. Sometimes the problem can be treated with surgery, antibiotics, or hormone therapy. If chromosomal problems are found in the parents, genetic counseling may be prescribed. To have a successful pregnancy, mothers are encouraged to have a complete medical workup before getting pregnant again, get early prenatal care, and follow their doctor's instructions. Repeated miscarriage often leads to grief and emotional stress. Grieving will help the parents accept the losses and move on with their lives. Parents who are having a difficult time dealing with their feelings should not hesitate to ask others for comfort and support, including their doctor, a support group, or a professional counselor. •
Pregnancy and Oral Health: Fact Sheet Source: AGD Impact. Academy of General Dentistry Impact. 26(3): 17. March 1998. Contact: Available from Academy of General Dentistry (AGD). 211 East Chicago Avenue, Suite 1200, Chicago, IL 60611-2670. Fax (312) 440-4300; E-mail:
[email protected]; http://www.agd.org. Summary: This brief fact sheet outlines oral health recommendations for women who are pregnant. Pregnancy can affect oral health, primarily by increasing certain hormones (estrogen and progesterone) that are linked to an increase in the amount of plaque on the teeth. If the plaque is not removed, it can cause gingivitis. So-called 'pregnancy gingivitis' affects most pregnant women to some degree, and generally begins to surface in the second trimester. If untreated, gingivitis can lead to periodontal disease, a more serious form of gum disease. The fact sheet also notes that pregnant women are at risk for developing pregnancy tumors, which are inflammatory and benign growths that develop when swollen gums become irritated. The fact sheet focuses on the prevention of these problems, and discusses a recommended schedule for dental care during pregnancy. A final section outlines dental procedures that should be avoided during pregnancy. 2 references. 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
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in some way to progesterone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: 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 progesterone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with progesterone. 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 progesterone. 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.
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To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “progesterone” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “progesterone”. 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 “progesterone” (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 “progesterone” (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.26
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
26
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)27: •
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/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
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
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
225
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
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
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
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
227
PROGESTERONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 17-Hydroxyprogesterone: A hydroxyprogesterone with medical uses similar to that of progesterone. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] 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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acrosome: Cap-like structure covering the nucleus and anterior part of the sperm head. [NIH]
Acrosome Reaction: Changes that occur to liberate the enzymes of the acrosome of spermatozoa that allow the entry of a spermatozoon into the ovum. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acyl: Chemical signal used by bacteria to communicate. [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] Adenoma: A benign epithelial tumor with a glandular organization. [NIH]
228 Progesterone
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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] 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] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]
Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [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
Dictionary 229
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] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] 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] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH]
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Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] 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]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [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
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origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] 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] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH]
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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] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anogenital: Pertaining to the anus and external genitals. [EU] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] 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
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specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH]
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Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors. [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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH]
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Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] 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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avian: A plasmodial infection in birds. [NIH] Avulsion: The forcible separation, or tearing away, of a part of an organ. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH]
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Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [NIH]
Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [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 agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU]
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Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] 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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] 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 Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a
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network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [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] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder)
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and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capecitabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
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Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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 Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH]
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Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH]
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Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] 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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Antagonists: Drugs that bind to but do not activate cholinergic receptors, thereby blocking the actions of acetylcholine or cholinergic agonists. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from
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the small intestines to the tissues. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of
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vitamins A and D. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Coitus: Sexual intercourse. [NIH] Colitis: Inflammation of the colon. [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] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comfrey: Perennial herb Symphytum officinale, in the family Boraginaceae, used topically for wound healing. It contains allantoin, carotene, essential oils (oils, volatile), glycosides, mucilage, resin, saponins, tannins, triterpenoids, vitamin B12, and zinc. Comfrey also contains pyrrolizidine alkaloids and is hepatotoxic if ingested. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in
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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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [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] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA
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or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [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] 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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Copulation: Sexual contact of a male with a receptive female usually followed by emission of sperm. Limited to non-human species. For humans use coitus. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
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]
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Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Coumestrol: A coumarin derivative occurring naturally in forage crops which has estrogenic activity. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] 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] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytochrome b5: A cytochrome occurring in the endoplasmic reticulum that acts as an intermediate electron carrier in some reactions catalyzed by mixed function oxidases, e.g., fatty acid desaturation. It further activates molecular oxygen for an attack on the substrate. MW 16kDa. [NIH]
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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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [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] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deja Vu: A subjective feeling that an experience which is occurring for the first time has been experienced before. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The
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three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] 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] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Device Removal: Removal of an implanted therapeutic or prosthetic device. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diethylstilbestrol: DES. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include
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neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydroprogesterone: 20 alpha-Hydroxypregn-4-en-3-one. progesterone derivative with progestational activity. [NIH]
A
naturally
occurring
Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by 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]
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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] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] 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 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Ductal carcinoma in situ: DCIS. Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called intraductal carcinoma. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [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] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [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] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH]
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Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] 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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Enanthate: An oily injectable contraceptive given every 8 weeks. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [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] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine
254 Progesterone
mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] 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]
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Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [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 carcinoma: Cancer that begins in the cells that line an organ. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting
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from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogen. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen receptor positive: ER+. Breast cancer cells that have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER+ need the hormone estrogen to grow and will usually respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Estrus Synchronization: Occurrence or induction of estrus in all of the females in a group at the same time, applies only to animals. [NIH] Ethinyl Estradiol: A semisynthetic estrogen with high oral estrogenic potency. It is often used as the estrogenic component in oral contraceptives. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH]
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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] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [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 Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling
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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]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [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] 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] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral,
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anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] 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] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Fluid: A fluid consisting of sex steroid hormones, plasma proteins, mucopolysaccharides, and electrolytes that is present in the vesicular ovarian follicle (Graafian follicle) surrounding the ovum. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored
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in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestation period: The period of development of the young from the time of conception until birth. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH]
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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] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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 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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to
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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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have
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failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] High-density lipoproteins: Lipoproteins that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [NIH]
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Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] 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]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] 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] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] 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] Hormones, Synthetic: Synthetic chemical compounds that mimic the activity of hormones produced in the body, but differ in structure from naturally occurring hormones. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [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] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic
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conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [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] 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] Hypersecretion: Excessive secretion. [EU] 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 an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglossal Nerve: The 12th cranial nerve. The hypoglossal nerve originates in the hypoglossal nucleus of the medulla and supplies motor innervation to all of the muscles of the tongue except the palatoglossus (which is supplied by the vagus). This nerve also contains proprioceptive afferents from the tongue muscles. [NIH]
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Hypophyseal: Hypophysial. [EU] 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] Hysterectomy: Excision of the uterus. [NIH] Hysterosalpingography: Radiography of the uterus and fallopian tubes after the injection of a contrast medium. [NIH] Hysteroscopy: Endoscopic examination, therapy or surgery of the interior of the uterus. [NIH]
Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]
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Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification, or release of tension at the time of committing the act. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [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
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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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoperable: Not suitable to be operated upon. [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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage
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requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [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] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraductal carcinoma: Abnormal cells that involve only the lining of a duct. The cells have not spread outside the duct to other tissues in the breast. Also called ductal carcinoma in situ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] 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]
Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after
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delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [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] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the
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cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactation: The period of the secretion of milk. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] 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] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [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] Lesion: An area of abnormal tissue change. [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]
Leukemia: Cancer of blood-forming tissue. [NIH]
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Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] 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] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [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] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH]
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Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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] Lordosis: The anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side. The term usually refers to abnormally increased curvature (hollow back, saddle back, swayback). It does not include lordosis as normal mating posture in certain animals ( = posture + sex behavior, animal). [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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 diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH]
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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant mesothelioma: A rare type of cancer in which malignant cells are found in the sac lining the chest or abdomen. Exposure to airborne asbestos particles increases one's risk of developing malignant mesothelioma. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Maternal Behavior: The behavior patterns associated with or characteristic of a mother. [NIH]
Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Eminence: Raised area on the infundibular hypothalamus at the floor of the third ventricle of the brain which contains the primary capillary network of the hypophyseal portal system. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical
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substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] 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] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious 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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH]
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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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] 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 Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesothelioma: A benign (noncancerous) or malignant (cancerous) tumor affecting the lining of the chest or abdomen. Exposure to asbestos particles in the air increases the risk of developing malignant mesothelioma. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Metribolone: A synthetic non-aromatizable androgen and anabolic steroid. It binds strongly to the androgen receptor and has therefore also been used as an affinity label for this receptor in the prostate and in prostatic tumors. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU]
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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Milk Ejection: Reflex in which tactile stimulation of nipples causes release of oxytocin which causes myoepithelial cells surrounding mammary alveoli to contract and expel the milk. Applies to humans and animals. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic Index: An expression of the number of mitoses found in a stated number of cells. [NIH]
Mixed Function Oxidases: Catalyse the insertion of one oxygen atom of molecular oxygen
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into the organ substrate. Require a second substrate to donate electrons for the reduction of the second atom in the oxygen molecule to water. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two 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] Monocyte: A type of white blood cell. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [NIH] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH]
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Motor Neurons: Neurons which activate muscle cells. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [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 Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] 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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myometrium: The smooth muscle coat of the uterus, which forms the main mass of the organ. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or
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stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
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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] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] Neutrophil: A type of white blood cell. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nidation: Implantation of the conceptus in the endometrium. [EU] Nipples: The conic organs which usually give outlet to milk from the mammary glands. [NIH]
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Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [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] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor
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of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Oestradiol: Growth hormone. [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]
Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncology: The study of cancer. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [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]
Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orderly: A male hospital attendant. [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] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a
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solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [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 Cysts: General term for cysts and cystic diseases of the ovary. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus
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brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH]
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Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pectins: High molecular weight polysaccharides present in the cell walls of all plants. Pectins cement cell walls together. They are used as emulsifiers and stabilizers in the food industry. They have been tried for a variety of therpeutic uses including as antidiarreals, where they are now generally considered ineffective, and in the treatment of hypercholesterolemia. [NIH] Pellucida: The hyaline or faintly radially striated oesinophilic membrane in immediate contact with the outer wall of the ovum. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Permissiveness: The attitude that grants freedom of expression and activity to another individual, but not necessarily with sanction or approval. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been
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associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [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] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH]
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Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoperiod: The time period of daily exposure that an organism receives from daylight or artificial light. It is believed that photoperiodic responses may affect the control of energy balance and thermoregulation. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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
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that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [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 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 Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [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]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH]
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Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] 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] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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] Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It
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pertains especially to the hepatic portal system. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [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 the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnenolone: Steroid hormone. [NIH] Premarin: A hormone replacement therapy drug developed by AHP (USA). [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH]
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Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [NIH] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary tumor: The original tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progesterone Reductase: An enzyme that catalyzes the reduction of a 3 beta-hydroxydelta(5)-steroid to 3-oxo-delta(4)-steroid in the presence of NAD. It converts pregnenolone to progesterone and dehydroepiandrosterone to androstenedione. EC 1.1.1.145. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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
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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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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
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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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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 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-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They
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function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychomotor Performance: The coordination of a sensory or ideational (cognitive) process and a motor activity. [NIH] 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] 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]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyrrolizidine Alkaloids: Alkaloids found in various species of Senecio and other plants. There are at least ten different chemicals, many of them hepatotoxic, teratogenic, and carcinogenic. The plants may cause damage in grazing herds, but no longer have medical use. [NIH]
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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] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] Receptor Cross-Talk: The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction. [NIH] Receptor, Insulin: A cell surface receptor for insulin. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precusor protein. The receptor contains an intrinsic tyrosine kinase domain that is located within the beta subunit. Activation of the receptor by insulin results in numerous metabolic changes including increased uptake of glucose into the liver, muscle, and adipose tissue. EC 2.7.11.-. [NIH]
Receptors, Estrogen: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. [NIH]
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Receptors, Progesterone: Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives. [NIH]
Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH]
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Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH]
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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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saccule: The smaller of the 2 sacs within the vestibule of the ear. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salpingostomy: Formation of an artificial opening in a fallopian tube. [NIH] Sapogenins: The aglucon moiety of a saponin molecule. It may be triterpenoid or steroid, usually spirostan, in nature. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Schistosoma: A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts. [NIH] Schistosoma mansoni: A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis. [NIH] Schistosomiasis mansoni: Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU]
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Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3.
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The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Behavior: Sexual activities of humans. [NIH] Sex Behavior, Animal: Sexual activities of animals. [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 sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell
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activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] 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] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [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] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall
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in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [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] Spasmodic: Of the nature of a spasm. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speculum: An instrument used to widen an opening of the body to make it easier to look inside. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sperm Count: A count of sperm in the ejaculum, expressed as number per milliliter. [NIH] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermatozoon: The mature male germ cell. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [EU] Squamous: Scaly, or platelike. [EU] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat,
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scaly cells. [NIH] Steady state: Dynamic equilibrium. [EU] 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] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU]
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Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprarenal: Above a kidney. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] 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] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [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] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific
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synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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 mammary and uterine. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [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] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Theca Cells: The connective tissue cells of the ovarian follicle. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases,
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palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for
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increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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 toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tragacanth: Powdered exudate from Astragalus gummifer and related plants. It forms gelatinous mass in water. Tragacanth is used as suspending agent, excipient or emulsifier in foods, cosmetics and pharmaceuticals. It has also been used as a bulk-forming laxative. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] 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]
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
Dictionary 309
protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transvaginal ultrasound: A procedure used to examine the vagina, uterus, fallopian tubes, and bladder. An instrument is inserted into the vagina, and sound waves bounce off organs inside the pelvic area. These sound waves create echoes, which a computer uses to create a picture called a sonogram. Also called TVS. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichosanthin: Plant-derived ribosome-inactivating protein purified from the Chinese medicinal herb tian-hua-fen which is obtained from the root tubers of Trichosanthes kirilowii. It has been used as an abortifacient and in the treatment of trophoblastic tumors. GLQ223 (Compound Q), a highly purified form of trichosanthin, has been proposed as antiviral treatment for AIDS. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trophic: Of or pertaining to nutrition. [EU] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic.
310 Progesterone
[NIH]
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] 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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] 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] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH]
Dictionary 311
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [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] 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] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU]
312 Progesterone
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 tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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]
Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [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]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] 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] 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] Xenopus: An aquatic genus of the family Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to
Dictionary 313
treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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] Zona Pellucida: The transport non-cellular envelope surrounding the mammalian ovum. [NIH]
Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
315
INDEX 1 17-Hydroxyprogesterone, 90, 95, 227 A Abdomen, 227, 238, 255, 269, 271, 273, 274, 276, 285, 286, 303, 304, 307, 310, 312 Abdominal, 227, 228, 266, 276, 285, 286, 292, 309, 310 Abdominal Pain, 227, 310 Aberrant, 11, 227 Ablate, 27, 227, 253 Ablation, 4, 27, 52, 227 Acceptor, 192, 227, 272, 284 Acetone, 185, 227, 270 Acetylcholine, 26, 29, 68, 109, 227, 242, 282 Acrosome, 114, 120, 129, 135, 227 Acrosome Reaction, 114, 120, 129, 135, 227 Actin, 227, 279 Acyl, 180, 227, 275 Adaptability, 227, 241 Adaptation, 227, 289 Adenine, 227, 228, 295 Adenocarcinoma, 67, 76, 88, 227 Adenoma, 96, 227 Adenosine, 71, 133, 228, 235, 239, 288 Adenosine Monophosphate, 133, 228 Adenovirus, 55, 228 Adenylate Cyclase, 9, 117, 228 Adipocytes, 59, 228, 245, 271 Adipose Tissue, 175, 228, 296 Adjunctive Therapy, 185, 228 Adjuvant, 61, 73, 101, 182, 228 Adrenal Cortex, 179, 228, 229, 231, 247, 256, 264, 265, 283, 292 Adrenal Medulla, 228, 240, 255, 282 Adrenergic, 31, 51, 117, 170, 228, 234, 251, 255, 305 Adrenergic Agents, 51, 228 Adverse Effect, 36, 165, 228, 301 Aerobic, 228, 277 Afferent, 33, 228, 271 Affinity, 37, 154, 164, 228, 229, 234, 276, 302 Agar, 228, 288 Agonist, 11, 27, 35, 39, 43, 46, 63, 70, 71, 81, 132, 170, 172, 181, 182, 229, 243, 251, 266, 279, 281, 296, 306 Air Sacs, 229, 230 Airway, 5, 132, 229, 302
Airway Obstruction, 132, 229 Aldosterone, 26, 73, 79, 229, 277 Alendronate, 153, 170, 229 Alertness, 229, 239 Algorithms, 229, 237 Alkaline, 229, 230, 239, 287 Alkaloid, 229, 236, 243, 278, 281 Allantois, 229, 258 Alleles, 17, 229, 263 Allergen, 229, 249, 300 Allograft, 23, 229 Alpha Particles, 229, 296 Alpha-helix, 229, 270 Alternative medicine, 195, 229 Alternative Splicing, 51, 229, 294 Alveoli, 30, 230, 277 Amenorrhea, 96, 137, 178, 184, 230, 282, 290 Amine, 230, 264 Amino Acid Motifs, 230, 245 Amino Acid Sequence, 152, 158, 175, 178, 230, 231, 232, 245, 257, 260, 293, 301 Amino Acids, 25, 230, 232, 245, 257, 260, 281, 286, 290, 294, 299, 301, 308, 310 Amino-terminal, 184, 230 Ammonia, 230, 310 Amnion, 12, 230, 258 Amniotic Fluid, 230 Amphetamines, 230, 243 Amplification, 33, 45, 80, 157, 230 Amygdala, 134, 230, 236, 272, 306 Anabolic, 37, 230, 250, 276 Anaesthesia, 230, 267 Anal, 57, 230, 255, 259 Analgesic, 33, 230, 266, 272, 278 Analog, 160, 230, 259 Analogous, 33, 230, 251, 308 Analytes, 56, 231 Anaphylatoxins, 231, 245 Anaphylaxis, 75, 231 Anaplasia, 231 Anatomical, 5, 34, 45, 58, 134, 231, 235, 246, 250, 253, 267, 281, 300 Androgen-Binding Protein, 231, 301 Androgenic, 37, 231, 282 Androgens, 37, 45, 154, 228, 231, 247, 265, 275 Androstenedione, 36, 138, 231, 292
316 Progesterone
Anemia, 209, 231, 259 Anesthesia, 34, 229, 231 Anesthetics, 231, 255 Aneuploidy, 81, 231 Aneurysm, 231, 311 Angina, 83, 176, 231 Angina Pectoris, 83, 176, 231 Angiogenesis, 55, 63, 232, 274 Angiotensinogen, 232, 298 Animal model, 15, 18, 22, 23, 27, 34, 49, 60, 101, 102, 176, 232 Annealing, 232, 290 Anogenital, 67, 232 Anovulation, 36, 232, 290 Antagonism, 93, 232, 239 Anterior Cruciate Ligament, 108, 232 Anthracycline, 126, 232, 248 Antiallergic, 232, 247 Antiandrogens, 154, 232, 236 Antibacterial, 232, 250, 303 Antibiotic, 69, 232, 248, 251, 277, 284, 286, 303 Antibodies, 48, 77, 175, 181, 182, 232, 255, 262, 264, 266, 273, 289 Antibody, 19, 42, 158, 228, 232, 233, 244, 262, 264, 266, 267, 275, 278, 301, 303 Anticoagulant, 232, 294 Anticonvulsant, 91, 232 Antidepressant, 232, 259 Antidiuretic, 232, 280 Antifungal, 232, 270 Antigen, 57, 108, 157, 228, 231, 232, 233, 244, 248, 255, 264, 265, 266, 267, 275, 292, 300 Antigen-Antibody Complex, 233, 244 Antigen-presenting cell, 233, 248 Anti-inflammatory, 11, 233, 247, 249, 261, 266, 285 Anti-Inflammatory Agents, 233, 247 Antimetabolite, 233, 249, 259 Antineoplastic, 162, 233, 247, 251, 259, 260, 275, 277, 284, 290, 311 Antioxidant, 38, 175, 233, 234, 259, 284 Antiproliferative, 96, 112, 126, 162, 182, 233 Antiseptic, 227, 233 Antiviral, 28, 233, 268, 309 Anus, 230, 232, 233, 235, 238, 297 Anxiety, 29, 37, 56, 134, 233 Anxiety Disorders, 56, 233 Anxiolytic, 29, 91, 233 Aorta, 119, 233, 240, 266, 311
Apnea, 5, 138, 233 Apolipoproteins, 233, 272 Apoptosis, 18, 19, 21, 34, 54, 84, 87, 103, 107, 130, 190, 233 Applicability, 7, 233 Approximate, 154, 233 Aqueous, 233, 236, 248, 253 Arachidonate 12-Lipoxygenase, 234, 273 Arachidonate 15-Lipoxygenase, 234, 273 Arachidonate Lipoxygenases, 234, 273 Arachidonic Acid, 234, 293 Arginine, 22, 175, 186, 231, 234, 282 Arrestins, 31, 234 Arterial, 82, 92, 99, 234, 242, 265, 294, 306 Arteries, 20, 176, 233, 234, 237, 238, 246, 266, 273, 276, 279 Arterioles, 234, 238, 239, 279 Arteriovenous, 184, 234 Asbestos, 234, 274, 276 Ascorbic Acid, 83, 129, 234, 265 Aseptic, 234, 283, 304 Assay, 12, 40, 57, 77, 84, 103, 155, 173, 174, 234 Astrocytes, 6, 38, 39, 234 Asymptomatic, 18, 234 Ataxia, 209, 235, 266, 306 ATP, 42, 228, 235, 251, 260, 270, 288, 294, 308 Atresia, 43, 235 Atrium, 235, 240, 311 Atrophy, 185, 208, 209, 235 Attenuated, 42, 235, 250 Atypical, 8, 80, 235 Auditory, 235, 274, 310 Autoimmune disease, 235 Autoimmunity, 79, 235 Autonomic, 26, 29, 227, 235, 282, 286 Autoradiography, 30, 36, 235 Avian, 42, 192, 235 Avulsion, 38, 235 Axillary, 73, 235 Axons, 235, 249, 295 Axotomy, 38, 235 B Bacteria, 227, 232, 233, 235, 236, 242, 249, 255, 257, 262, 264, 276, 277, 296, 303, 308, 310 Bactericidal, 162, 235 Bacteriophage, 235, 288, 308 Basal Ganglia, 235, 236, 272, 282 Basal Ganglia Diseases, 235, 236
Index 317
Base, 158, 227, 236, 248, 260, 270, 282, 287, 295, 306 Basement Membrane, 236, 240, 257 Basophils, 236, 262, 272 Benign, 44, 75, 80, 96, 110, 111, 215, 227, 236, 258, 262, 271, 276, 280, 312 Beta-Galactosidase, 52, 236 Beta-Thromboglobulin, 236, 269 Bewilderment, 236, 245 Bicalutamide, 37, 236 Bicuculline, 42, 236 Bilateral, 236, 290, 309 Bile, 180, 236, 259, 273, 304 Bile Acids, 180, 236, 304 Bile Acids and Salts, 236 Binding agent, 68, 184, 236 Binding Sites, 59, 236 Bioavailability, 37, 62, 236 Biodegradation, 157, 169, 237 Biological Markers, 61, 237 Biological response modifier, 237, 268 Biological therapy, 237, 262 Biological Transport, 237, 250 Biomarkers, 94, 174, 237 Biopsy, 215, 237, 286 Biosynthesis, 127, 234, 237, 256, 294, 301 Biotechnology, 63, 71, 161, 191, 195, 205, 207, 208, 209, 210, 237 Bladder, 3, 130, 237, 265, 269, 281, 294, 309, 310 Blastocyst, 36, 237, 245, 253, 284, 288, 309 Blood Coagulation, 237, 239, 307 Blood Glucose, 155, 237, 263, 268 Blood Platelets, 237, 289, 301 Blood pressure, 237, 240, 265, 278, 302 Blood Volume, 10, 238 Blot, 4, 42, 62, 238 Body Fluids, 237, 238, 252, 259, 282, 302, 309 Body Mass Index, 18, 238 Bone Density, 46, 238 Bone Marrow, 238, 266, 273, 275, 302, 304 Bowel, 157, 230, 238, 250, 268, 269, 271, 286, 299, 310 Bowel Movement, 238, 250 Bradykinin, 238, 282, 289 Brain Injuries, 32, 84, 238 Brain Stem, 238, 241 Branch, 223, 238, 253, 273, 274, 285, 303, 306 Breeding, 144, 185, 238 Bronchi, 238, 255, 308
Bronchial, 238, 264, 293 Bronchioles, 230, 238 Bronchiseptica, 238, 287 Bronchitis, 238, 242 Bulimia, 16, 56, 238 C Cachexia, 170, 239 Caffeine, 175, 239, 295 Calcium Channels, 107, 133, 239 Callus, 239, 253 Calmodulin, 29, 239 Capecitabine, 61, 239 Capillary, 238, 239, 274, 290, 311 Capsules, 239, 251 Carbohydrate, 46, 104, 120, 239, 247, 290 Carbon Dioxide, 239, 248, 259, 288, 298 Carcinogen, 24, 41, 44, 239, 256, 275 Carcinogenesis, 15, 57, 166, 239 Carcinogenic, 239, 268, 293, 295, 304, 309 Carcinoma in Situ, 240 Cardiac, 20, 126, 153, 170, 239, 240, 255, 256, 279, 304 Cardiology, 20, 83, 109, 240 Cardiopulmonary, 66, 240 Cardiopulmonary Bypass, 66, 240 Cardiovascular, 10, 20, 46, 51, 92, 99, 158, 166, 172, 176, 177, 239, 240, 301, 311 Cardiovascular disease, 20, 52, 166, 172, 176, 240 Cardiovascular System, 20, 46, 51, 177, 240 Carnitine, 175, 240 Carotene, 129, 240, 244, 298 Carpal Tunnel Syndrome, 183, 240 Case report, 75, 240, 243 Catecholamine, 240, 251 Catheterization, 20, 240, 269 Caudal, 240, 249, 266, 282, 291 Caudate Nucleus, 236, 240, 282 Cause of Death, 39, 172, 176, 240 Celiac Disease, 157, 240 Cell Aggregation, 240, 284 Cell Count, 39, 241 Cell Cycle, 8, 44, 48, 58, 81, 84, 241, 247, 256, 292, 295 Cell Death, 38, 54, 233, 241, 256, 280 Cell Differentiation, 36, 88, 241, 301 Cell Division, 208, 235, 241, 256, 262, 269, 275, 277, 288, 293, 300 Cell membrane, 237, 239, 241, 249, 270, 285, 288, 291, 312 Cell motility, 241, 263
318 Progesterone
Cell proliferation, 8, 19, 29, 36, 44, 46, 57, 60, 68, 99, 114, 120, 158, 172, 241, 301 Cell Respiration, 241, 277, 298 Cell Survival, 241, 262 Cellobiose, 241 Cellulose, 169, 241, 288 Central Nervous System, 100, 227, 230, 239, 241, 243, 252, 260, 262, 278, 287, 301 Cerebellar, 235, 241, 297 Cerebellum, 238, 241, 297 Cerebral, 10, 38, 39, 235, 238, 241, 246, 255, 256, 258, 295, 306, 307 Cerebral hemispheres, 235, 238, 241 Cerebrovascular, 10, 236, 240, 241, 306 Cerebrum, 241, 309 Ceroid, 174, 241, 272 Cervical, 15, 19, 28, 116, 242, 273, 274 Cervix, 19, 73, 116, 242, 298 Chaperonins, 242, 278 Character, 231, 242, 261 Chemotactic Factors, 242, 245 Chemotaxis, 29, 242 Chemotherapy, 61, 82, 103, 109, 126, 242 Cholesterol, 153, 170, 179, 236, 242, 246, 263, 265, 272, 273, 275, 296, 299, 304, 306 Cholesterol Esters, 242, 272 Cholinergic, 14, 242, 281 Cholinergic Antagonists, 14, 242 Chorion, 12, 93, 242, 258 Chromaffin System, 242, 253 Chromatin, 28, 53, 67, 69, 78, 97, 192, 233, 242, 282, 303 Chromosomal, 215, 230, 231, 242 Chromosome, 105, 231, 242, 262, 263, 272, 278, 300, 309, 310 Chronic Disease, 239, 242, 244 Chronic Obstructive Pulmonary Disease, 77, 242 Chronic renal, 242, 290 Chylomicrons, 242, 272 Circulatory system, 243, 253 CIS, 14, 159, 179, 243, 298 Citrus, 234, 243 Clamp, 243, 285 Clear cell carcinoma, 243, 249 Clinical Medicine, 243, 291 Clinical study, 243, 246 Clinical trial, 4, 32, 40, 43, 61, 147, 149, 182, 205, 243, 246, 294, 296 Clomiphene, 90, 243 Clone, 7, 243 Cloning, 9, 48, 67, 237, 243
Coagulation, 159, 237, 243, 263, 289, 307 Coca, 243 Cocaine, 9, 16, 243 Cod Liver Oil, 243, 253 Coenzyme, 175, 234, 244, 271 Cofactor, 70, 244, 294, 307 Cognition, 18, 37, 244 Coitus, 244, 246 Colitis, 157, 244 Collagen, 19, 236, 244, 257, 258, 264, 274, 289, 293 Collagen disease, 244, 264 Collapse, 231, 244, 302 Combination Therapy, 166, 244, 256 Comfrey, 183, 244 Complement, 22, 40, 231, 244, 245, 260, 274, 289, 301 Complementary and alternative medicine, 125, 141, 245 Complementary medicine, 125, 245 Computational Biology, 205, 207, 245 Conception, 91, 245, 246, 258, 260, 291, 304 Concomitant, 30, 153, 170, 245 Conduction, 245, 306 Cone, 234, 245 Confusion, 127, 245, 250 Congestion, 245, 255 Congestive heart failure, 170, 245 Conjugated, 104, 116, 165, 177, 198, 236, 245, 247 Conjunctiva, 89, 245 Connective Tissue, 234, 238, 244, 245, 258, 260, 273, 276, 298, 299, 304, 306 Connective Tissue Cells, 245, 306 Consciousness, 230, 245, 248, 250, 251 Consensus Sequence, 59, 154, 230, 245, 246 Conserved Sequence, 230, 245 Constriction, 246, 270, 311 Constriction, Pathologic, 246, 311 Consumption, 165, 246, 249, 284 Contraception, 3, 41, 71, 74, 75, 76, 97, 100, 126, 164, 166, 180, 182, 184, 246, 272, 282 Contraceptive, 26, 34, 45, 74, 92, 133, 165, 166, 198, 246, 253, 275, 282 Contractility, 19, 35, 246 Contraindications, ii, 246 Controlled clinical trial, 43, 246 Controlled study, 40, 246 Convulsions, 232, 236, 246, 252, 281, 291 Coordination, 241, 246, 295 Copulation, 37, 246 Cornea, 246, 299, 304
Index 319
Coronary, 20, 46, 166, 172, 176, 231, 240, 246, 263, 276, 279 Coronary Arteriosclerosis, 246, 279 Coronary Circulation, 231, 246 Coronary heart disease, 46, 166, 172, 176, 240, 246, 263 Coronary Thrombosis, 246, 276, 279 Corpus, 98, 119, 120, 161, 191, 246, 273, 286, 292, 307 Corpus Luteum, 98, 119, 120, 161, 191, 246, 273, 292 Cortex, 7, 167, 179, 235, 246, 254, 256, 258, 295, 297 Cortical, 71, 246, 257, 280, 295, 300, 306 Corticosteroid, 145, 179, 247, 291 Cortisol, 10, 16, 77, 90, 93, 104, 117, 149, 247 Cortisone, 247, 249 Coumarin, 247 Coumestrol, 130, 247 Cranial, 241, 247, 262, 265, 286, 310 Crossing-over, 247, 297 Cues, 16, 247 Curative, 247, 307 Cutaneous, 26, 178, 247, 273, 285 Cyclic, 35, 62, 63, 69, 79, 97, 130, 133, 145, 228, 239, 247, 262, 282, 293, 300 Cyclin, 8, 44, 58, 68, 70, 163, 247 Cytochrome, 67, 94, 247 Cytochrome b, 67, 94, 247 Cytochrome b5, 67, 94, 247 Cytokine, 11, 29, 88, 143, 248, 269 Cytoplasm, 177, 233, 236, 241, 248, 254, 255, 262, 299 Cytotoxic, 32, 248, 302 Cytotoxicity, 99, 248 D Databases, Bibliographic, 205, 248 Daunorubicin, 248, 251 Deamination, 248, 310 Decarboxylation, 248, 264, 279 Decidua, 11, 12, 248, 277, 288 Dehydroepiandrosterone, 79, 96, 104, 248, 292 Deja Vu, 98, 248 Deletion, 52, 95, 233, 248 Dementia, 19, 248, 250 Denaturation, 248, 290 Dendrites, 248, 249, 281, 295 Dendritic, 28, 248, 275 Dendritic cell, 28, 248
Density, 75, 76, 153, 170, 238, 248, 272, 283, 290, 303 Dental Care, 215, 248 Dental Caries, 248, 259 Dentate Gyrus, 10, 249, 264 Deoxyribonucleic, 249, 299 Deoxyribonucleic acid, 249, 299 Deoxyuridine, 19, 249 Depolarization, 249, 302 Dermatitis, 75, 249 Desensitization, 56, 249 Deuterium, 249, 265 Developed Countries, 176, 249 Device Removal, 156, 249 Dexamethasone, 117, 118, 249 Diabetes Mellitus, 98, 249, 261, 263 Diagnostic procedure, 151, 195, 249 Dialysate, 17, 249 Diastolic, 249, 265 Diencephalon, 249, 266, 307 Diethylstilbestrol, 177, 249 Diffuse Axonal Injury, 238, 249 Diffusion, 168, 237, 250, 270 Digestion, 236, 238, 250, 269, 273, 304 Digestive system, 150, 250, 279 Dihydroprogesterone, 64, 109, 250 Dihydrotestosterone, 250, 297, 301 Dihydroxy, 162, 229, 250 Dilatation, 231, 250, 292, 311 Dilatation, Pathologic, 250, 311 Dilation, 238, 250, 311 Dilution, 156, 169, 176, 250, 255, 289 Dimerization, 65, 66, 92, 250 Diploid, 231, 250, 278, 288, 290, 309 Direct, iii, 22, 26, 58, 197, 243, 250, 251, 297, 305 Disease-Free Survival, 46, 250 Disinfection, 117, 250 Disorientation, 245, 250 Disparity, 23, 250 Disposition, 61, 250 Dissection, 53, 135, 250, 309 Dissociation, 6, 42, 157, 169, 228, 250 Dissociative Disorders, 250, 251 Distal, 26, 251, 295 Diuresis, 239, 251 Diurnal, 41, 251 Dizziness, 165, 251 DNA Topoisomerase, 251, 260 Dopamine, 17, 68, 243, 251, 287 Dorsal, 17, 251, 291 Dorsum, 251
320 Progesterone
Dosage Forms, 168, 251 Dose-dependent, 117, 251 Doxorubicin, 61, 71, 133, 251 Drive, ii, vi, 45, 60, 115, 251, 267, 270, 272 Drug Design, 37, 251 Drug Interactions, 198, 199, 251 Drug Tolerance, 252, 307 Duct, 71, 240, 252, 257, 269, 299 Ductal carcinoma in situ, 74, 252, 269 Duodenum, 236, 252, 304 Dwarfism, 153, 170, 252 Dyes, 157, 169, 236, 252 Dynorphins, 252, 283 Dysmenorrhea, 137, 180, 252 Dyspareunia, 252, 256 Dysphoric, 88, 252 Dysplasia, 209, 252 Dystrophy, 209, 252 E Eating Disorders, 16, 252 Eclampsia, 236, 252, 291 Ectopic, 13, 98, 111, 159, 252 Ectopic Pregnancy, 98, 159, 252 Edema, 38, 39, 252, 291 Effector, 26, 227, 244, 252, 281 Effector cell, 252, 281 Efficacy, 9, 37, 43, 45, 65, 132, 155, 175, 251, 252 Elastin, 244, 252, 257 Elective, 106, 252 Electrocardiogram, 20, 109, 252 Electrocoagulation, 243, 253 Electrolyte, 229, 247, 253, 259, 277, 282, 291, 302 Electrons, 233, 236, 253, 270, 278, 284, 296 Electrophysiological, 45, 51, 253 Embryo Transfer, 116, 161, 187, 253, 291 Embryogenesis, 59, 253 Emphysema, 242, 253 Emulsion, 157, 170, 235, 253, 259 Enamel, 248, 253, 270 Enanthate, 135, 253 Encapsulated, 157, 169, 253 Endocrine Glands, 253 Endocrine System, 13, 190, 253, 281 Endometriosis, 21, 44, 84, 132, 137, 152, 180, 182, 184, 190, 253, 272, 282 Endopeptidases, 254, 294 Endorphins, 254, 283, 293 Endothelial cell, 52, 83, 93, 254, 258, 269, 307 Endothelium, 52, 254, 282, 289
Endothelium, Lymphatic, 254 Endothelium, Vascular, 254 Endothelium-derived, 254, 282 Endotoxins, 244, 254, 270 End-stage renal, 242, 254, 290 Energy balance, 254, 271, 288 Enhancer, 254, 298 Enkephalin, 33, 254, 293 Entorhinal Cortex, 254, 264 Environmental Exposure, 237, 254, 283 Environmental Health, 204, 206, 254 Enzymatic, 239, 240, 244, 248, 254, 264, 290, 298 Eosinophil, 11, 255 Eosinophilic, 157, 190, 255 Eosinophilic Gastroenteritis, 157, 255 Epidemiologic Studies, 237, 255 Epidermal, 76, 81, 99, 128, 255, 270, 275, 312 Epidermal Growth Factor, 76, 81, 99, 128, 255 Epidermis, 255, 270 Epigastric, 255, 285 Epinephrine, 90, 228, 251, 255, 282, 310 Epithelial carcinoma, 163, 255 Epithelial Cells, 8, 21, 30, 52, 57, 62, 66, 68, 103, 106, 159, 163, 179, 255, 263, 277 Epithelial ovarian cancer, 82, 255 Epithelium, 8, 15, 18, 19, 28, 30, 44, 54, 55, 57, 60, 166, 236, 254, 255, 285 Epitopes, 177, 255 Erythema, 75, 255, 310 Erythrocyte Volume, 238, 255 Erythrocytes, 108, 231, 238, 255, 297, 301 Esophagitis, 157, 255 Esophagus, 235, 250, 255, 287, 303, 304 Essential Tremor, 209, 255 Estradiol, 6, 7, 12, 13, 16, 20, 24, 30, 32, 34, 36, 41, 44, 45, 55, 58, 59, 60, 65, 77, 82, 83, 84, 88, 89, 96, 97, 103, 104, 105, 107, 108, 109, 111, 113, 117, 118, 119, 120, 125, 126, 127, 128, 130, 132, 139, 143, 144, 145, 165, 169, 177, 178, 198, 256, 301 Estriol, 97, 108, 177, 256 Estrogen Antagonists, 14, 256 Estrogen receptor positive, 183, 256 Estrogen Replacement Therapy, 46, 72, 256 Estrone, 21, 108, 165, 177, 256 Estrus Synchronization, 172, 256 Ethinyl Estradiol, 104, 177, 256 Ethnic Groups, 104, 256
Index 321
Etoposide, 126, 127, 256 Eukaryotic Cells, 256, 267, 283, 310 Evoke, 256, 304 Excipient, 168, 256, 308 Excitability, 51, 256, 279 Excitation, 51, 230, 257 Excitatory, 257, 261, 266, 281 Excitatory Amino Acids, 257, 281 Exhaustion, 232, 257 Exocrine, 257, 285 Exogenous, 12, 15, 18, 20, 59, 153, 170, 257, 260 Exon, 95, 100, 229, 257 Expiration, 257, 298 Extensor, 257, 295 Extracellular, 11, 114, 120, 134, 234, 245, 257, 258, 274, 302 Extracellular Matrix, 11, 245, 257, 258, 274 Extracellular Matrix Proteins, 257, 274 Extracellular Space, 257 Extraction, 179, 257 Extrapyramidal, 251, 257 Exudate, 257, 308 Eye Infections, 228, 257 F Fallopian Tubes, 257, 266, 298, 309 Family Planning, 205, 257 Fatigue, 184, 258, 262 Fatty acids, 153, 170, 258, 273, 293 Femoral, 240, 258 Femoral Artery, 240, 258 Femur, 232, 258 Ferritin, 104, 258 Fertilization in Vitro, 258, 291 Fetal Membranes, 88, 258 Fetus, 12, 48, 61, 145, 166, 214, 258, 259, 266, 288, 292, 303, 304, 310 Fibrinogen, 258, 289, 307 Fibroblast Growth Factor, 55, 258 Fibroblasts, 59, 86, 110, 155, 245, 258, 269 Fibroid, 148, 258, 271 Fibronectin, 14, 258 Fibrosis, 209, 258, 300 Fissure, 249, 258 Fixation, 258, 301 Fluid Therapy, 259, 282 Fluorescence, 103, 259 Fluorine, 132, 259 Fluorouracil, 61, 127, 259 Fluoxetine, 56, 259 Foetoplacental, 259, 283 Folate, 175, 249, 259
Fold, 28, 57, 167, 174, 258, 259 Folic Acid, 122, 259 Follicles, 9, 34, 49, 90, 149, 259, 268 Follicular Fluid, 114, 117, 120, 259 Follicular Phase, 16, 78, 259 Fungi, 232, 257, 259, 276, 277, 313 G Galactosides, 236, 259 Gallate, 125, 259 Gallbladder, 227, 250, 259 Ganglia, 227, 236, 260, 280, 286 Gas, 230, 239, 250, 259, 260, 265, 282, 298, 305 Gastric, 240, 251, 255, 260, 264 Gastrin, 260, 264 Gastrointestinal, 62, 234, 238, 255, 258, 260, 271, 301, 305, 309, 311 Gastrointestinal tract, 258, 260, 271, 301, 309 Gene Expression, 4, 22, 23, 24, 29, 35, 53, 55, 58, 61, 68, 73, 81, 181, 209, 260 Gene Targeting, 34, 260 Generator, 41, 260 Genetic Code, 260, 282 Genetic Counseling, 215, 260 Genetic Engineering, 237, 243, 260 Genetic testing, 260, 290 Genistein, 128, 134, 165, 260 Genital, 28, 68, 72, 215, 243, 260, 269, 310 Genitourinary, 260, 310 Genotype, 17, 260, 287 Germ Cells, 260, 275, 283, 284, 302, 303, 306, 313 Gestation, 12, 33, 48, 50, 51, 88, 160, 172, 214, 260, 288, 303 Gestation period, 160, 260 Gestational, 12, 98, 260 Glottis, 261, 287 Glucose, 68, 85, 99, 110, 155, 208, 234, 237, 241, 249, 261, 263, 268, 296 Glucose Intolerance, 249, 261 Glucuronic Acid, 261, 263 Glutamate, 261, 287 Glutathione Peroxidase, 261, 300 Gluten, 240, 261 Glycine, 236, 261, 301 Glycols, 261, 265 Glycoprotein, 60, 62, 127, 131, 155, 258, 261, 301, 307 Goats, 160, 261 Gonad, 31, 261 Gonadal, 5, 14, 17, 18, 31, 41, 190, 261, 304
322 Progesterone
Gonadotropin, 31, 33, 36, 41, 45, 47, 64, 81, 82, 87, 89, 132, 152, 261 Governing Board, 261, 291 Grade, 62, 79, 80, 261 Graft, 261, 264, 267 Grafting, 262, 267 Granule, 249, 262, 299 Granulocytes, 190, 262, 271, 302, 312 Granulosa Cells, 9, 49, 63, 66, 105, 109, 111, 112, 117, 118, 128, 129, 132, 136, 155, 262, 268, 273 Gravidity, 262, 285 Growth factors, 46, 262 Guanylate Cyclase, 262, 282 H Hair follicles, 262, 312 Haloperidol, 23, 262 Haploid, 262, 288, 290 Haplotypes, 18, 262 Haptens, 228, 262 Headache, 239, 262, 292 Heart attack, 240, 262 Heart failure, 262 Heat-Shock Proteins, 262, 278 Heat-Shock Proteins 90, 262, 278 Heme, 247, 262, 284 Hemin, 69, 262 Hemiparesis, 238, 262 Hemodialysis, 249, 262 Hemodynamics, 46, 263 Hemoglobin, 231, 255, 262, 263 Hemoglobinuria, 208, 263 Hemorrhage, 253, 262, 263, 304 Hemorrhoids, 157, 263 Hemostasis, 263, 301 Heparin, 11, 263, 289 Hepatic, 144, 263, 291 Hepatocyte, 30, 263 Hepatocyte Growth Factor, 30, 263 Hepatotoxic, 244, 263, 295 Hereditary, 263, 298 Heredity, 260, 263 Heterochromatin, 184, 263 Heterogeneity, 171, 228, 263 Heterozygote, 57, 263 High-density lipoproteins, 83, 263 Hippocampus, 7, 11, 91, 249, 264, 272, 295, 305 Hirsutism, 264, 265 Histamine, 109, 231, 264 Histidine, 264 Histology, 56, 104, 264, 285
Homeostasis, 10, 26, 68, 170, 264 Homodimer, 264, 308 Homologous, 27, 229, 247, 260, 263, 264, 300, 301, 305 Hormonal therapy, 156, 169, 264 Hormone therapy, 154, 168, 215, 264, 275 Hormones, Synthetic, 154, 264 Host, 28, 174, 179, 181, 235, 264, 266, 267, 299, 312 Human growth hormone, 79, 264 Human papillomavirus, 15, 67, 264 Hybrid, 23, 52, 55, 243, 264 Hybridomas, 264, 269 Hydrocortisone, 88, 179, 264 Hydrolysis, 42, 236, 241, 265, 270, 288, 290, 294 Hydronephrosis, 3, 265 Hydrophobic, 265, 272 Hydroxides, 265 Hydroxyl Radical, 25, 265 Hydroxylation, 143, 162, 265 Hydroxylysine, 244, 265 Hydroxyproline, 244, 265 Hyperandrogenism, 36, 40, 265 Hypercholesterolemia, 265, 286 Hyperplasia, 8, 46, 265 Hypersecretion, 36, 96, 265 Hypersensitivity, 229, 231, 249, 255, 265, 298, 300 Hyperstimulation, 19, 187, 265 Hypertension, 10, 26, 108, 126, 240, 262, 265, 291 Hypertrophy, 265 Hypnotic, 40, 265 Hypoglossal Nerve, 38, 265 Hypophyseal, 266, 274 Hypothalamic, 4, 6, 31, 32, 35, 37, 45, 56, 64, 128, 266 Hypothalamus, 7, 11, 30, 34, 35, 56, 58, 117, 192, 249, 254, 266, 272, 274, 288, 292, 293, 307 Hypoxia, 5, 266, 306 Hysterectomy, 116, 148, 266 Hysterosalpingography, 215, 266 Hysteroscopy, 215, 266 I Ibotenic Acid, 266, 279 Ibuprofen, 156, 169, 266 Id, 121, 136, 216, 222, 224, 266 Idiopathic, 193, 266 Iliac Artery, 83, 258, 266 Immune function, 23, 266, 308
Index 323
Immune response, 29, 157, 181, 228, 232, 233, 235, 247, 262, 266, 274, 300, 305, 312 Immune system, 23, 182, 215, 233, 235, 237, 252, 266, 267, 273, 274, 310, 312 Immune Tolerance, 22, 266 Immunization, 266, 267, 300 Immunodeficiency, 208, 266 Immunoglobulin, 232, 266, 278 Immunohistochemistry, 4, 12, 19, 30, 103, 266 Immunology, 75, 84, 88, 99, 102, 110, 228, 266 Immunophilin, 67, 266 Immunosuppressant, 259, 266 Immunosuppressive, 23, 162, 261, 266, 267 Immunotherapy, 237, 249, 267 Impairment, 15, 40, 55, 235, 236, 257, 267, 276 Implantation, 14, 22, 27, 54, 55, 89, 101, 109, 130, 152, 166, 187, 245, 267, 281, 283, 284 Impulse Control Disorders, 56, 267 In situ, 4, 11, 30, 35, 47, 58, 267 In Situ Hybridization, 4, 11, 30, 35, 47, 58, 267 Incision, 267, 269 Incubated, 83, 267 Incubation, 267, 287 Incubation period, 267, 287 Indicative, 161, 171, 185, 189, 267, 285, 311 Induction, 13, 17, 19, 21, 22, 31, 38, 47, 59, 60, 64, 98, 111, 117, 128, 182, 231, 256, 267, 292 Infancy, 267 Infantile, 174, 267 Infarction, 267 Infertility, 9, 32, 33, 36, 43, 45, 47, 55, 72, 152, 186, 193, 214, 267 Inflammation, 157, 183, 186, 233, 238, 244, 249, 255, 257, 258, 264, 268, 298, 306, 310, 312 Inflammatory bowel disease, 157, 268 Infusion, 12, 38, 43, 90, 132, 268 Inhibin, 31, 268 Initiation, 13, 26, 39, 48, 69, 72, 268, 293, 308 Innervation, 26, 265, 268, 274 Inoperable, 185, 268 Inotropic, 251, 268 Insecticides, 268, 287, 312 Insight, 5, 9, 11, 36, 39, 47, 52, 268 Insomnia, 184, 268, 292
Insulin, 13, 36, 59, 69, 79, 81, 87, 98, 99, 109, 112, 129, 130, 136, 155, 268, 270, 296 Insulin-dependent diabetes mellitus, 268 Insulin-like, 13, 69, 79, 87, 98, 109, 112, 136, 268 Interferon, 75, 92, 132, 268 Interferon-alpha, 92, 268 Interleukin-1, 66, 83, 91, 268, 269 Interleukin-10, 66, 269 Interleukin-2, 92, 269 Interleukin-6, 82, 269 Interleukin-8, 66, 269 Intermittent, 5, 259, 269, 286 Internal Medicine, 135, 253, 269 Interphase, 263, 269 Intestinal, 240, 269, 274, 299, 311, 313 Intestine, 236, 238, 269, 271 Intoxication, 269, 312 Intracellular Membranes, 269, 275 Intraductal carcinoma, 252, 269 Intramuscular, 75, 92, 269 Intrathecal, 33, 269 Intravenous, 10, 43, 268, 269 Intravesical, 103, 269 Intrinsic, 228, 236, 269, 296 Intubation, 240, 269 Invasive, 80, 93, 152, 163, 269, 274 Involuntary, 236, 255, 269, 279, 302 Involution, 68, 116, 269 Ion Channels, 28, 234, 270, 281, 306 Ion Transport, 270, 277 Ions, 236, 239, 250, 253, 265, 270, 275, 291 Ischemia, 38, 235, 270, 281 J Joint, 106, 270, 305, 306 K Kb, 204, 270 Keratin, 15, 270 Keratinocytes, 269, 270 Keto, 130, 270 Ketoconazole, 118, 270 Ketone Bodies, 227, 270 Ketosis, 185, 270 Kidney Disease, 150, 204, 209, 215, 265, 270 Kidney Pelvis, 271, 310 Kidney stone, 265, 271 Kinetics, 111, 239, 271 L Labile, 244, 271 Labyrinth, 271, 311 Lactate Dehydrogenase, 185, 271
324 Progesterone
Lactation, 35, 185, 271, 283, 284, 292 Laparoscopy, 215, 271 Large Intestine, 250, 255, 269, 271, 297, 302 Larynx, 261, 271, 308, 310 Latency, 40, 58, 271 Laxative, 228, 271, 308 Lectin, 271, 275 Leiomyoma, 148, 258, 271, 302 Leiomyosarcoma, 85, 271 Leptin, 59, 82, 97, 127, 271 Lesion, 171, 271, 273 Lethal, 23, 34, 64, 126, 176, 235, 271 Leucocyte, 255, 271 Leukemia, 87, 208, 251, 271 Leukocytes, 162, 236, 238, 242, 262, 268, 272 Levo, 272, 275, 282 Levonorgestrel, 79, 168, 272, 282 Libido, 231, 272 Library Services, 222, 272 Life cycle, 228, 259, 272 Ligament, 232, 272, 294 Ligands, 23, 37, 168, 181, 182, 272, 296 Ligation, 38, 272 Limbic, 230, 272 Limbic System, 230, 272 Linkages, 25, 263, 272 Lipid, 20, 59, 110, 112, 119, 120, 129, 132, 157, 166, 169, 233, 241, 268, 270, 272, 275, 284, 309 Lipid Peroxidation, 272, 284 Lipofuscin, 241, 272 Lipoprotein, 46, 272, 273 Liposomes, 157, 169, 272 Lipoxygenase, 120, 234, 273 Lobe, 264, 273, 285, 293 Localization, 9, 22, 44, 49, 50, 55, 57, 61, 86, 113, 144, 266, 273 Localized, 47, 49, 57, 61, 238, 248, 253, 259, 264, 267, 273, 288, 310 Loop, 4, 107, 273 Lordosis, 30, 38, 144, 273 Low-density lipoprotein, 272, 273 Lumbar, 33, 273 Lupus, 273, 306 Luteal Phase, 26, 34, 83, 91, 118, 129, 191, 273, 277 Lutein Cells, 81, 273, 292 Lymph, 163, 235, 242, 243, 254, 273, 297, 305 Lymph node, 163, 235, 242, 273, 297
Lymphatic, 152, 254, 267, 273, 276, 302, 303, 307 Lymphatic system, 273, 302, 303, 307 Lymphocyte, 99, 233, 273, 274, 275 Lymphoid, 232, 271, 273, 274 Lymphoma, 87, 208, 274 M Macrophage, 268, 274 Magnetic Resonance Imaging, 148, 274 Major Histocompatibility Complex, 262, 274 Malabsorption, 208, 240, 274 Malignancy, 8, 41, 274, 285 Malignant, 8, 66, 80, 85, 86, 103, 111, 208, 227, 233, 240, 274, 276, 280, 293, 299, 306 Malignant mesothelioma, 274, 276 Malnutrition, 235, 239, 274, 279 Mastitis, 185, 186, 274 Maternal Behavior, 13, 35, 58, 274 Matrix metalloproteinase, 47, 105, 110, 274 Meatus, 274, 310 Medial, 58, 274, 283 Median Eminence, 34, 274 Median Nerve, 240, 274 Mediate, 4, 6, 21, 24, 34, 38, 50, 52, 54, 56, 60, 68, 85, 251, 274, 278 Mediator, 22, 31, 60, 98, 269, 274, 289, 301 MEDLINE, 205, 207, 209, 275 Medullary, 80, 275 Megaloblastic, 249, 259, 275 Megestrol, 92, 127, 275 Megestrol Acetate, 127, 275 Meiosis, 275, 305, 310 Melanin, 275, 287, 310 Melanocytes, 275 Melanoma, 208, 275 Melphalan, 127, 275 Membrane, 4, 12, 23, 29, 35, 42, 56, 61, 62, 63, 64, 67, 69, 73, 91, 93, 94, 108, 168, 174, 175, 208, 230, 234, 241, 242, 245, 249, 254, 256, 270, 271, 272, 275, 279, 283, 284, 285, 286, 288, 291, 294, 302, 305, 309, 313 Membrane Fluidity, 91, 108, 275 Membrane Glycoproteins, 275 Membrane Potentials, 29, 275 Membrane Proteins, 56, 272, 275 Memory, 14, 18, 40, 190, 192, 248, 276 Meninges, 241, 276 Menstruation, 22, 152, 159, 177, 214, 230, 248, 252, 259, 273, 276, 283, 292 Mental Disorders, 150, 276, 295
Index 325
Mental Health, iv, 4, 24, 88, 150, 204, 206, 276 Mental Processes, 250, 276, 295 Mental Retardation, 25, 210, 276 Mesenchymal, 255, 276 Mesentery, 276, 286 Mesoderm, 276, 309, 313 Mesothelioma, 75, 274, 276 Metabolite, 40, 64, 68, 90, 91, 109, 153, 159, 162, 179, 194, 256, 276, 292 Metaplasia, 152, 276 Metastasis, 62, 163, 274, 276 Metastatic, 92, 132, 147, 174, 185, 276, 300 Methyltransferase, 183, 276 Metribolone, 167, 276 MI, 214, 225, 276 Microbe, 276, 308 Microbiological, 180, 276 Microbiology, 227, 235, 276, 277 Microorganism, 244, 277, 285, 312 Microscopy, 19, 49, 236, 277 Microtubules, 277, 285 Microwaves, 277, 296 Mifepristone, 100, 109, 140, 277 Milk Ejection, 35, 277 Milliliter, 238, 277, 303 Mineralocorticoid, 10, 26, 71, 105, 168, 277 Miscarriage, 137, 214, 277 Mitochondria, 71, 78, 131, 242, 277, 283 Mitochondrial Swelling, 277, 280 Mitomycin, 126, 133, 277 Mitosis, 43, 233, 277 Mitotic, 42, 59, 60, 120, 256, 277, 278, 311 Mitotic Index, 60, 277 Mixed Function Oxidases, 247, 277 Mobility, 170, 278 Mobilization, 12, 153, 170, 278 Modeling, 251, 278 Modification, 37, 67, 97, 260, 278, 296 Modulator, 78, 95, 148, 164, 278 Molecular Chaperones, 6, 42, 242, 262, 278 Monitor, 28, 34, 43, 73, 185, 278, 282 Monoclonal, 19, 264, 278 Monocyte, 84, 278 Monosomy, 231, 278 Mood Disorders, 8, 278 Morphine, 278, 280 Morphogenesis, 30, 54, 278 Morphological, 33, 41, 253, 275, 278 Morphology, 116, 135, 278 Morula, 237, 278 Motility, 175, 278, 301
Motor Activity, 246, 278, 295 Motor Neurons, 38, 279 Mucosa, 28, 62, 240, 273, 279, 280, 292, 304, 311, 313 Mucositis, 279, 307 Mucus, 279, 310 Muscimol, 36, 279 Muscle Contraction, 51, 231, 279 Muscle Fibers, 279 Muscular Atrophy, 209, 279 Muscular Dystrophies, 252, 279 Mutagenesis, 52, 107, 279 Mutagens, 279 Myocardial infarction, 236, 246, 276, 279 Myocardial Ischemia, 176, 231, 279 Myocardium, 231, 276, 279 Myometrium, 12, 48, 87, 190, 192, 279 Myosin, 279 Myotonic Dystrophy, 209, 279 N Narcosis, 279 Narcotic, 33, 278, 279 Nasal Cavity, 100, 280 Nasal Septum, 280 Nausea, 94, 251, 270, 280, 292 NCI, 1, 150, 203, 243, 280 Necrosis, 88, 190, 233, 267, 276, 279, 280 Need, 3, 46, 148, 176, 192, 215, 217, 228, 242, 256, 274, 280, 307 Neonatal, 21, 60, 65, 280 Neonatal period, 21, 280 Neoplasia, 8, 15, 67, 114, 208, 280 Neoplasm, 280, 299, 310 Neoplastic, 15, 85, 90, 144, 181, 190, 231, 264, 274, 280 Nephrogenic, 54, 280 Nephron, 26, 280 Nephropathy, 271, 280 Nerve, 14, 26, 32, 38, 228, 231, 235, 248, 265, 268, 274, 275, 280, 281, 291, 299, 300, 304, 309, 310 Nervous System, 5, 209, 228, 235, 241, 274, 280, 281, 286, 305, 306 Networks, 54, 101, 280 Neural, 8, 13, 19, 24, 29, 39, 45, 58, 228, 280 Neural Pathways, 45, 280 Neurobehavioral Manifestations, 238, 250, 280 Neuroendocrine, 31, 40, 56, 281 Neuroendocrinology, 40, 117, 189, 281 Neurogenic, 100, 281 Neurologic, 238, 281
326 Progesterone
Neuromuscular, 227, 281, 306 Neuromuscular Junction, 227, 281 Neuronal, 6, 32, 33, 35, 39, 45, 68, 174, 235, 239, 279, 281 Neuropeptide, 8, 35, 82, 281 Neuroprotective Agents, 84, 281 Neurosecretory Systems, 253, 281 Neurotoxic, 58, 266, 279, 281 Neurotoxin, 58, 281 Neurotransmitters, 45, 257, 281 Neutrons, 229, 281, 296 Neutrophil, 107, 281 Nicotine, 29, 281 Nidation, 253, 281 Nipples, 277, 281 Nitric Oxide, 22, 31, 108, 119, 282 Nitrogen, 144, 185, 229, 230, 231, 257, 259, 275, 282, 309 Norepinephrine, 26, 30, 228, 251, 282 Norethindrone, 79, 104, 165, 282 Norgestrel, 165, 272, 282 Nuclei, 5, 35, 171, 229, 230, 253, 260, 272, 274, 277, 281, 282, 289, 294 Nucleic acid, 53, 152, 175, 181, 260, 267, 279, 282, 295, 297, 299 Nucleosomes, 74, 282 Nucleus Accumbens, 17, 282 Nutritional Support, 82, 282 O Odds Ratio, 282, 297 Oestradiol, 91, 117, 120, 129, 158, 283 Oestrogen, 74, 76, 78, 89, 95, 108, 111, 112, 129, 171, 190, 283 Ointments, 251, 283, 285 Oligomenorrhea, 283, 290 Oncogene, 98, 103, 208, 263, 283 Oncology, 81, 92, 94, 101, 111, 127, 129, 283, 297 Oocytes, 9, 36, 58, 69, 70, 283 Opacity, 248, 283 Opioid Peptides, 34, 252, 254, 283 Optic Chiasm, 266, 283, 292 Oral Health, 215, 283 Orderly, 44, 283 Organ Culture, 28, 283, 307 Organelles, 248, 275, 283, 285 Osmosis, 283 Osmotic, 38, 277, 283 Osteoclasts, 159, 179, 284 Osteoporosis, 96, 137, 138, 158, 159, 166, 170, 178, 185, 189, 191, 229, 256, 283, 284, 296
Ovarian Cysts, 117, 284 Ovarian epithelial cancer, 91, 284 Ovarian Follicle, 45, 47, 144, 246, 259, 262, 284, 306 Ovariectomy, 10, 18, 55, 284 Ovaries, 34, 37, 149, 163, 182, 255, 257, 265, 284, 290, 297, 298, 301, 306 Ovary, 9, 36, 42, 64, 80, 95, 105, 155, 161, 163, 173, 231, 246, 256, 261, 283, 284, 304 Ovum, 155, 227, 246, 248, 259, 260, 272, 278, 284, 286, 292, 309, 312, 313 Ovum Implantation, 284, 309 Oxidation, 179, 227, 233, 234, 247, 261, 272, 284 Oxidative Stress, 39, 284 Oxygen Consumption, 284, 298 Oxygenase, 79, 284 Oxygenator, 240, 284 Oxytetracycline, 116, 284 Oxytocin, 7, 21, 25, 35, 49, 68, 84, 88, 109, 144, 186, 277, 284 P P53 gene, 96, 284 Paclitaxel, 126, 284 Palliative, 185, 275, 283, 285, 307 Pancreas, 155, 227, 237, 250, 268, 285, 309 Pancreatic, 76, 155, 208, 240, 285 Pancreatic cancer, 208, 285 Papillomavirus, 285 Paraffin, 61, 84, 89, 285 Paralysis, 262, 285, 306 Parasite, 285, 299 Paresthesia, 285, 306 Parietal, 285, 286 Parity, 18, 285 Paroxysmal, 208, 231, 285, 287, 312 Particle, 285, 303, 308 Parturition, 12, 35, 48, 72, 86, 117, 161, 285, 292 Patch, 29, 285, 308 Patch-Clamp Techniques, 29, 285 Pathogen, 157, 267, 285 Pathogenesis, 30, 50, 285 Pathologic, 50, 233, 237, 246, 265, 285, 295, 298 Pathologic Processes, 233, 285 Pathologies, 60, 158, 286 Pathophysiology, 32, 50, 286 Patient Education, 214, 220, 222, 225, 286 Pectins, 169, 286 Pellucida, 114, 120, 286 Pelvic, 148, 152, 254, 286, 294, 309
Index 327
Penicillin, 232, 286 Penis, 286, 298 Peptide, 31, 34, 35, 45, 73, 134, 185, 254, 258, 270, 271, 283, 286, 290, 293, 294 Percutaneous, 20, 286 Perfusion, 266, 286 Pericardium, 286, 306 Periodontal disease, 215, 286 Peripheral blood, 268, 286 Peripheral Nervous System, 286, 305, 311 Peritoneal, 152, 249, 286 Peritoneal Dialysis, 249, 286 Peritoneum, 75, 276, 286 Permissiveness, 28, 286 Pertussis, 114, 120, 286, 312 Pesticides, 237, 268, 287 Petrolatum, 253, 287 Petroleum, 285, 287 PH, 70, 99, 238, 287 Pharmaceutical Preparations, 241, 287 Pharmaceutical Solutions, 251, 287 Pharmacokinetic, 37, 126, 287 Pharmacologic, 37, 96, 231, 287, 308 Pharynx, 280, 287, 310 Phenobarbital, 61, 287 Phenolphthalein, 253, 287 Phenotype, 41, 57, 93, 237, 287 Phenyl, 166, 180, 287 Phenylalanine, 287, 310 Phorbol, 31, 287, 294 Phorbol Esters, 287, 294 Phospholipases, 288, 302 Phospholipids, 258, 272, 275, 288, 294 Phosphorus, 239, 288 Phosphorylated, 234, 244, 288 Phosphorylates, 288, 294 Phosphorylating, 51, 288 Phosphorylation, 8, 44, 45, 48, 63, 66, 67, 69, 70, 88, 135, 288, 294 Photocoagulation, 243, 288 Photoperiod, 190, 288 Photoreceptors, 234, 288 Physical Examination, 148, 288 Physiologic, 27, 229, 237, 276, 288, 293, 296, 297, 298 Pigment, 241, 272, 275, 288 Pilot study, 22, 43, 288 Pituitary Gland, 155, 247, 258, 288, 293 Placenta, 23, 60, 116, 256, 259, 288, 292 Plants, 229, 236, 238, 239, 243, 261, 271, 278, 282, 286, 288, 295, 299, 308, 309 Plaque, 215, 288
Plasma cells, 232, 289 Plasma protein, 254, 259, 289 Plasma Volume, 238, 277, 289 Plasmin, 289 Plasminogen, 47, 289 Plasminogen Activators, 289 Plasticity, 5, 8, 13, 35, 289 Platelet Activation, 289, 302 Platelet Aggregation, 231, 282, 289 Platelet Factor 4, 269, 289 Platelets, 234, 236, 282, 289, 307 Platinum, 273, 289 Pleated, 270, 289 Pleomorphic, 282, 289 Ploidy, 95, 290 Podophyllotoxin, 256, 290 Polycystic, 36, 40, 45, 105, 110, 209, 265, 290 Polycystic Ovary Syndrome, 40, 110, 265, 290 Polyethylene, 168, 290 Polyethylene Glycols, 169, 290 Polymerase, 103, 290, 293 Polymerase Chain Reaction, 103, 290 Polymers, 169, 290, 294 Polymorphic, 249, 290 Polymorphism, 17, 18, 63, 72, 74, 94, 290 Polypeptide, 4, 9, 117, 230, 244, 245, 255, 258, 289, 290, 292, 294, 311, 313 Polysaccharide, 233, 241, 290 Portal System, 136, 274, 290 Posterior, 230, 235, 241, 251, 284, 285, 291, 299 Postnatal, 291, 304 Postsynaptic, 291, 301, 305, 306 Post-translational, 184, 231, 291, 301 Post-traumatic, 238, 291 Potassium, 45, 51, 229, 275, 277, 291 Potassium Channels, 51, 291 Potentiate, 70, 291 Potentiating, 17, 133, 291 Potentiation, 117, 291, 302 Practice Guidelines, 206, 291 Precipitation, 157, 170, 291 Preclinical, 32, 79, 291 Precursor, 32, 231, 232, 234, 251, 252, 254, 282, 287, 289, 291, 292, 293, 308, 309, 310 Prednisolone, 133, 156, 169, 291 Preeclampsia, 50, 291 Pregnancy Outcome, 36, 291 Pregnenolone, 32, 38, 76, 140, 179, 291, 292 Premarin, 153, 170, 291
328 Progesterone
Premenopausal, 70, 89, 172, 291 Premenstrual, 56, 65, 88, 138, 145, 177, 190, 192, 194, 214, 292 Premenstrual Syndrome, 56, 65, 138, 145, 190, 192, 194, 214, 292 Prenatal, 17, 215, 253, 292 Prenatal Care, 215, 292 Preoptic Area, 30, 58, 292 Presumptive, 57, 292 Prevalence, 17, 27, 283, 292 Primary tumor, 62, 292 Probe, 29, 149, 292 Prodrug, 153, 292 Progeny, 160, 292 Progesterone Reductase, 69, 292 Progestogen, 46, 74, 108, 178, 292 Prognostic factor, 86, 163, 292 Progression, 6, 15, 18, 41, 45, 47, 54, 57, 61, 84, 163, 232, 292 Progressive, 12, 241, 242, 248, 252, 256, 262, 270, 279, 280, 289, 292, 310 Projection, 282, 292, 295, 297 Prolactin, 11, 13, 14, 30, 58, 59, 94, 97, 104, 109, 120, 128, 292 Proliferating Cell Nuclear Antigen, 19, 292 Proline, 52, 244, 265, 293 Promoter, 10, 14, 15, 25, 49, 50, 54, 62, 63, 72, 78, 97, 154, 293 Promotor, 293, 298 Pro-Opiomelanocortin, 254, 283, 293 Prophase, 283, 293, 305, 310 Prospective study, 71, 94, 113, 126, 172, 293 Prostaglandin, 19, 26, 47, 48, 49, 66, 119, 130, 132, 144, 293 Prostaglandins A, 293 Prostaglandins F, 277, 293 Prostate, 154, 167, 175, 177, 208, 237, 276, 283, 294, 298, 309 Protease, 28, 55, 80, 244, 294 Protease Inhibitors, 28, 294 Protein C, 31, 48, 170, 230, 233, 235, 258, 270, 272, 282, 294, 310 Protein Conformation, 230, 270, 294 Protein Isoforms, 229, 294 Protein Kinase C, 131, 294 Protein S, 181, 191, 209, 210, 237, 245, 260, 264, 294, 297, 299 Proteins, 6, 7, 8, 11, 14, 23, 24, 31, 42, 44, 47, 52, 53, 59, 73, 86, 100, 158, 174, 178, 179, 180, 181, 182, 184, 192, 229, 230,
231, 233, 234, 238, 241, 242, 244, 247, 257, 262, 264, 268, 270, 274, 275, 278, 282, 286, 288, 289, 290, 294, 296, 297, 299, 300, 301, 307, 308 Protein-Tyrosine Kinase, 260, 294 Proteinuria, 291, 294 Proteolytic, 9, 25, 244, 258, 289, 294 Protocol, 81, 166, 294 Protons, 229, 265, 294, 296 Proto-Oncogene Proteins, 285, 294 Proto-Oncogene Proteins c-mos, 285, 294 Protozoa, 276, 277, 295 Proximal, 38, 251, 280, 295 Psoriasis, 157, 295 Psychiatric, 11, 16, 237, 276, 295 Psychiatry, 14, 21, 30, 39, 130, 258, 295, 304 Psychic, 272, 295, 300 Psychology, 7, 16, 250, 295 Psychomotor, 14, 295 Psychomotor Performance, 14, 295 Puberty, 24, 31, 33, 295 Public Policy, 205, 295 Publishing, 63, 191, 295 Pulmonary, 177, 237, 246, 255, 295, 298, 311 Pulse, 34, 40, 45, 278, 295 Purines, 295, 301 Pyramidal Cells, 249, 295 Pyrrolizidine Alkaloids, 244, 295 Q Quality of Life, 20, 40, 112, 148, 296 Quiescent, 23, 296 R Race, 153, 272, 275, 282, 296 Radiation, 69, 215, 231, 235, 254, 259, 266, 296, 312 Radio Waves, 148, 277, 296 Radioactive, 235, 265, 267, 282, 296, 309 Radiological, 286, 296 Radiopharmaceutical, 260, 296 Raloxifene, 82, 88, 296, 300 Randomized, 10, 43, 61, 72, 92, 97, 103, 110, 113, 133, 135, 252, 296 Reactive Oxygen Species, 38, 158, 296 Reagent, 56, 296 Receptivity, 4, 27, 68, 166, 296 Receptor Cross-Talk, 79, 296 Receptor, Insulin, 36, 296 Receptors, Estrogen, 89, 296 Receptors, Progesterone, 9, 88, 108, 297 Receptors, Serotonin, 297, 301 Recombinant, 59, 83, 134, 179, 297, 311
Index 329
Recombination, 27, 260, 297 Recovery of Function, 39, 297 Rectal, 173, 297 Rectum, 157, 233, 238, 250, 260, 268, 271, 294, 297 Recur, 183, 297 Recurrence, 61, 297 Red blood cells, 255, 284, 297 Red Nucleus, 235, 297 Reductase, 12, 64, 70, 134, 297 Refer, 1, 244, 251, 254, 258, 259, 273, 281, 297, 311 Regeneration, 258, 297 Regimen, 144, 252, 297 Regional lymph node, 28, 297 Relapse, 61, 110, 297 Relative risk, 17, 297 Relaxant, 22, 297 Relaxin, 19, 297 Reliability, 70, 160, 298 Remission, 297, 298 Renin, 26, 50, 232, 298 Reproduction Techniques, 291, 298 Reproductive system, 175, 298 Resorption, 284, 298 Respiration, 5, 233, 239, 258, 278, 298 Respiratory System, 229, 298, 311 Response Elements, 10, 49, 50, 67, 298 Retinal, 245, 250, 283, 298 Retinoblastoma, 208, 298 Retinoid, 129, 298 Retrograde, 152, 269, 298 Rheumatism, 266, 298 Rheumatoid, 90, 244, 298 Rheumatoid arthritis, 90, 244, 298 Ribonuclease, 12, 299 Ribonucleic acid, 36, 93, 299 Ribose, 228, 299, 307 Ribosome, 299, 309 Risk factor, 16, 17, 41, 255, 293, 297, 299 Rod, 234, 243, 299 S Saccule, 299, 311 Saline, 148, 299 Saliva, 299 Salivary, 16, 77, 86, 118, 250, 285, 299, 305 Salivary glands, 250, 299 Salpingostomy, 111, 299 Sapogenins, 180, 299 Saponin, 299 Sarcoma, 79, 299 Schistosoma, 120, 299
Schistosoma mansoni, 120, 299 Schistosomiasis mansoni, 299 Schizoid, 299, 312 Schizophrenia, 299, 312 Schizotypal Personality Disorder, 299, 312 Sclera, 245, 299 Scleroproteins, 270, 300 Sclerosis, 209, 244, 300 Screening, 52, 130, 161, 172, 176, 183, 243, 300 Sebaceous, 300, 312 Second Messenger Systems, 281, 300 Secondary tumor, 276, 300 Secretory, 11, 14, 80, 167, 300, 305 Sedative, 40, 300 Segregation, 297, 300 Seizures, 145, 285, 300 Selective estrogen receptor modulator, 296, 300, 306 Selenium, 128, 175, 300 Sella, 251, 288, 300 Semen, 294, 300 Seminiferous tubule, 231, 268, 300, 303 Semisynthetic, 256, 300 Senile, 284, 300 Sensitization, 17, 300 Sensor, 160, 161, 301 Sequencing, 48, 50, 290, 301 Serine, 55, 67, 70, 254, 294, 295, 301 Serotonin, 5, 10, 56, 130, 144, 259, 297, 301, 309 Serous, 254, 301 Sex Behavior, 273, 301 Sex Behavior, Animal, 273, 301 Sex Characteristics, 231, 283, 295, 301, 306 Sex Determination, 209, 301 Sex Hormone-Binding Globulin, 78, 104, 108, 301 Sharpness, 171, 301 Shock, 42, 65, 67, 90, 231, 242, 264, 301, 309 Side effect, 19, 117, 119, 132, 183, 197, 228, 237, 301, 308 Signal Transduction, 6, 8, 30, 56, 262, 296, 301 Signs and Symptoms, 297, 298, 302 Skeletal, 153, 170, 177, 231, 243, 252, 279, 302 Skeleton, 78, 227, 258, 270, 293, 302 Skull, 302, 306 Sleep apnea, 5, 40, 302 Small intestine, 243, 252, 255, 264, 269, 302 Smooth Muscle Tumor, 258, 302
330 Progesterone
Sneezing, 287, 302 Social Environment, 296, 302 Social Isolation, 24, 64, 299, 302 Sodium, 26, 58, 169, 229, 275, 277, 302 Soft tissue, 94, 238, 302 Solid tumor, 232, 251, 302 Solvent, 157, 170, 227, 283, 287, 302 Soma, 295, 302 Somatic, 24, 59, 253, 272, 275, 277, 286, 302, 303, 306, 310 Somatic cells, 59, 275, 277, 303 Sonogram, 303, 309 Sound wave, 149, 245, 303, 309, 310 Spasmodic, 287, 303 Spatial disorientation, 251, 303 Specialist, 216, 250, 303 Species, 19, 22, 45, 246, 255, 264, 275, 277, 278, 285, 295, 296, 299, 303, 305, 309, 312 Specificity, 27, 37, 43, 60, 62, 164, 167, 228, 234, 239, 254, 303 Spectrum, 270, 277, 296, 303 Speculum, 149, 303 Sperm, 67, 100, 107, 114, 120, 129, 133, 135, 136, 175, 227, 231, 242, 246, 300, 303 Sperm Count, 175, 303 Sperm Head, 227, 303 Spermatozoa, 119, 131, 134, 135, 227, 300, 303 Spermatozoon, 227, 303 Spinal cord, 234, 238, 241, 242, 269, 274, 276, 280, 281, 286, 303 Spleen, 273, 299, 303 Spontaneous Abortion, 138, 291, 303 Sporadic, 298, 303 Spotting, 148, 303 Squamous, 15, 303 Squamous Epithelium, 15, 303 Steady state, 43, 304 Stem Cells, 34, 54, 57, 304 Sterility, 72, 82, 83, 87, 88, 90, 105, 112, 113, 126, 129, 132, 134, 152, 268, 304 Stillbirth, 291, 304 Stimulant, 239, 264, 304 Stimulus, 60, 158, 246, 251, 252, 257, 268, 269, 270, 271, 304, 307 Stomach, 227, 250, 255, 260, 264, 270, 280, 287, 302, 303, 304 Strand, 290, 304 Stress, 8, 16, 20, 29, 37, 51, 138, 184, 215, 240, 242, 247, 280, 284, 298, 304, 310 Striatum, 17, 282, 304 Stroke, 6, 150, 176, 204, 240, 281, 304
Stroma, 11, 15, 30, 60, 70, 304 Stromal, 14, 19, 21, 30, 41, 50, 52, 59, 60, 79, 163, 254, 304 Stromal Cells, 19, 50, 163, 304 Structure-Activity Relationship, 37, 304 Stupor, 279, 280, 304 Subacute, 32, 267, 304 Subclinical, 267, 300, 304 Subcutaneous, 228, 252, 271, 305 Subiculum, 264, 305 Submaxillary, 255, 305 Subspecies, 303, 305 Substance P, 276, 292, 300, 305 Substrate, 62, 98, 247, 278, 305 Suction, 285, 305 Supplementation, 59, 83, 125, 128, 129, 132, 305 Support group, 215, 305 Suppression, 23, 70, 80, 99, 152, 184, 247, 249, 296, 305 Suprarenal, 167, 305 Survival Rate, 163, 305 Sympathomimetic, 251, 255, 282, 305 Symphysis, 294, 305 Synapses, 281, 305 Synapsis, 305 Synaptic, 4, 45, 281, 302, 305 Synaptic Transmission, 281, 305 Synergistic, 97, 108, 190, 292, 306 Systemic, 39, 52, 62, 159, 176, 178, 198, 215, 231, 233, 237, 244, 255, 263, 267, 290, 291, 306 Systemic lupus erythematosus, 215, 244, 306 Systolic, 265, 306 T Tamoxifen, 14, 65, 73, 101, 108, 177, 300, 306 Telangiectasia, 209, 306 Telomerase, 34, 81, 306 Temporal, 9, 41, 49, 54, 70, 187, 230, 264, 274, 306 Temporal Lobe, 230, 306 Testicular, 191, 306 Testis, 118, 177, 231, 256, 283, 306 Testosterone, 5, 10, 34, 69, 96, 117, 130, 135, 145, 156, 169, 186, 231, 297, 301, 306 Tetrahydrocannabinol, 68, 306 Tetrodotoxin, 58, 306 Thalamic, 235, 306 Thalamic Diseases, 235, 306 Theca Cells, 47, 49, 135, 144, 273, 306
Index 331
Therapeutics, 10, 44, 56, 199, 306 Thermal, 161, 234, 250, 262, 281, 290, 307 Thermoregulation, 288, 307 Third Ventricle, 266, 274, 307 Thorax, 227, 273, 307, 310 Threonine, 294, 295, 301, 307 Threshold, 15, 26, 256, 265, 307 Thrombin, 258, 289, 294, 307 Thrombolytic, 289, 307 Thrombomodulin, 294, 307 Thrombosis, 236, 294, 304, 307 Thrombus, 246, 267, 279, 289, 307 Thymidine, 60, 61, 307 Thymidine Phosphorylase, 61, 307 Thymus, 68, 141, 266, 273, 307 Thyroid, 53, 85, 155, 158, 159, 179, 215, 307, 310 Thyroid Gland, 307 Thyroid Hormones, 159, 179, 307, 310 Tin, 240, 285, 289, 307 Tissue Culture, 44, 307 Tolerance, 23, 33, 227, 261, 262, 307 Tomography, 238, 308 Topical, 112, 136, 178, 182, 186, 285, 287, 308 Toxaemia, 291, 308 Toxic, iv, 61, 183, 215, 248, 254, 263, 275, 281, 290, 300, 308 Toxicity, 155, 251, 308 Toxicology, 117, 130, 206, 308 Toxins, 183, 233, 239, 254, 261, 267, 308 Trace element, 259, 307, 308 Trachea, 238, 271, 287, 307, 308 Tragacanth, 169, 308 Transcriptase, 306, 308 Transcription Factors, 13, 45, 53, 54, 59, 154, 164, 168, 298, 308 Transdermal, 112, 113, 118, 182, 183, 308 Transduction, 8, 14, 31, 301, 308 Transfection, 22, 50, 52, 119, 237, 308 Transforming Growth Factor beta, 104, 308 Translation, 9, 177, 308 Translational, 48, 309 Transmitter, 227, 234, 251, 257, 270, 275, 282, 305, 309 Transplantation, 41, 152, 242, 253, 266, 274, 309 Transvaginal ultrasound, 149, 309 Trauma, 43, 236, 238, 255, 262, 280, 281, 297, 306, 309 Trichosanthin, 129, 309
Triglyceride, 83, 309 Trisomy, 231, 309 Trophic, 14, 18, 309 Trophoblast, 11, 55, 61, 82, 93, 155, 237, 309 Tropism, 28, 309 Truncal, 153, 170, 309 Tryptophan, 244, 301, 309 Tubercle, 282, 309 Tuberculosis, 246, 273, 309 Tuberous Sclerosis, 209, 309 Tumor marker, 61, 237, 309 Tumor suppressor gene, 284, 309 Tumorigenic, 64, 91, 309 Tumour, 73, 88, 190, 310 Tyrosine, 8, 45, 55, 69, 119, 128, 131, 134, 135, 136, 251, 294, 296, 310 U Ubiquitin, 46, 136, 310 Ulcerative colitis, 157, 268, 310 Ultrasound test, 148, 310 Unconscious, 231, 266, 310 Univalent, 265, 284, 310 Urea, 144, 185, 310 Ureter, 3, 265, 271, 310 Urethra, 3, 286, 294, 310 Urinary, 3, 70, 130, 260, 310 Urinary tract, 3, 310 Urine, 148, 160, 232, 237, 251, 255, 256, 263, 265, 270, 271, 280, 294, 310 Urogenital, 177, 260, 310 Urticaria, 107, 231, 310 Uterine Contraction, 51, 284, 310 V Vaccine, 228, 294, 310 Vagina, 136, 149, 242, 249, 276, 298, 303, 309, 310 Vaginal, 15, 28, 62, 84, 103, 104, 111, 113, 116, 119, 156, 160, 185, 194, 310 Vagus Nerve, 38, 309, 310 Vascular, 10, 22, 46, 47, 52, 55, 63, 82, 84, 99, 152, 172, 174, 176, 231, 254, 267, 282, 284, 288, 289, 307, 310, 311 Vascular endothelial growth factor, 47, 82, 84, 311 Vasoactive, 117, 311 Vasoactive Intestinal Peptide, 117, 311 Vasoconstriction, 10, 26, 255, 311 Vasodilation, 26, 311 Vasodilator, 26, 238, 251, 264, 311 Vasomotor, 26, 112, 185, 256, 311 Vector, 308, 311
332 Progesterone
Vein, 148, 231, 234, 269, 282, 311 Venous, 234, 236, 263, 294, 311 Ventral, 266, 282, 311 Ventricle, 230, 240, 264, 282, 295, 306, 307, 311 Venules, 238, 239, 254, 311 Vesicular, 259, 262, 311 Vestibular, 156, 311 Vestibule, 29, 299, 311 Veterinary Medicine, 118, 120, 205, 311 Villous, 240, 311 Vinblastine, 131, 132, 311 Vinca Alkaloids, 311 Vincristine, 131, 133, 311 Viral, 28, 308, 309, 311, 312 Virilism, 265, 312 Virulence, 235, 308, 312 Virus, 25, 28, 67, 80, 235, 254, 260, 264, 268, 269, 288, 308, 311, 312 Viscera, 276, 303, 312 Visceral, 33, 272, 286, 310, 312 Visceral Afferents, 310, 312 Vitro, 8, 9, 10, 11, 18, 22, 24, 30, 35, 36, 37, 38, 39, 42, 47, 50, 55, 61, 62, 66, 75, 80, 81, 89, 90, 91, 127, 129, 154, 155, 163, 180, 187, 191, 240, 253, 263, 267, 290, 307, 312
Vivo, 8, 9, 10, 11, 13, 21, 22, 24, 30, 37, 38, 39, 44, 45, 47, 55, 62, 63, 64, 67, 72, 80, 81, 89, 90, 105, 110, 145, 154, 162, 180, 263, 267, 312 Voltage-gated, 29, 312 Vulgaris, 141, 312 W Warts, 264, 290, 312 Weight Gain, 59, 191, 312 White blood cell, 232, 255, 267, 272, 273, 274, 278, 279, 281, 289, 312 Whooping Cough, 287, 312 Windpipe, 287, 307, 312 Withdrawal, 12, 134, 312 Womb, 298, 310, 312 Wound Healing, 170, 244, 258, 274, 312 X Xenobiotics, 61, 312 Xenograft, 60, 152, 232, 312 Xenopus, 58, 66, 69, 70, 125, 312 X-ray, 238, 259, 282, 312 Y Yeasts, 259, 287, 313 Yolk Sac, 258, 313 Z Zona Pellucida, 107, 313 Zygote, 245, 313 Zymogen, 294, 313
Index 333
334 Progesterone
Index 335
336 Progesterone
