MALE
INFERTILITY 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., 1960Male Infertility: 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: 0-597-84489-5 1. Male Infertility-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 male infertility. 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 MALE INFERTILITY .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Male Infertility.............................................................................. 5 E-Journals: PubMed Central ....................................................................................................... 51 The National Library of Medicine: PubMed ................................................................................ 52 CHAPTER 2. NUTRITION AND MALE INFERTILITY .......................................................................... 95 Overview...................................................................................................................................... 95 Finding Nutrition Studies on Male Infertility ............................................................................ 95 Federal Resources on Nutrition ................................................................................................... 96 Additional Web Resources ........................................................................................................... 97 CHAPTER 3. CLINICAL TRIALS AND MALE INFERTILITY ................................................................ 99 Overview...................................................................................................................................... 99 Recent Trials on Male Infertility ................................................................................................. 99 Keeping Current on Clinical Trials ........................................................................................... 100 CHAPTER 4. PATENTS ON MALE INFERTILITY .............................................................................. 103 Overview.................................................................................................................................... 103 Patents on Male Infertility......................................................................................................... 103 Patent Applications on Male Infertility..................................................................................... 113 Keeping Current ........................................................................................................................ 122 CHAPTER 5. BOOKS ON MALE INFERTILITY .................................................................................. 123 Overview.................................................................................................................................... 123 Book Summaries: Federal Agencies............................................................................................ 123 Book Summaries: Online Booksellers......................................................................................... 126 Chapters on Male Infertility ...................................................................................................... 128 CHAPTER 6. PERIODICALS AND NEWS ON MALE INFERTILITY .................................................... 131 Overview.................................................................................................................................... 131 News Services and Press Releases.............................................................................................. 131 Academic Periodicals covering Male Infertility ......................................................................... 134 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 135 Overview.................................................................................................................................... 135 U.S. Pharmacopeia..................................................................................................................... 135 Commercial Databases ............................................................................................................... 136 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 141 Overview.................................................................................................................................... 141 NIH Guidelines.......................................................................................................................... 141 NIH Databases........................................................................................................................... 143 Other Commercial Databases..................................................................................................... 145 The Genome Project and Male Infertility................................................................................... 145 APPENDIX B. PATIENT RESOURCES ............................................................................................... 149 Overview.................................................................................................................................... 149 Patient Guideline Sources.......................................................................................................... 149 Finding Associations.................................................................................................................. 154 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 157 Overview.................................................................................................................................... 157 Preparation................................................................................................................................. 157 Finding a Local Medical Library................................................................................................ 157 Medical Libraries in the U.S. and Canada ................................................................................. 157 ONLINE GLOSSARIES................................................................................................................ 163
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Online Dictionary Directories ................................................................................................... 163 MALE INFERTILITY DICTIONARY......................................................................................... 165 INDEX .............................................................................................................................................. 233
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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 male infertility 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 male infertility, 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 male infertility, 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 male infertility. 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 male infertility, 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 male infertility. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON MALE INFERTILITY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on male infertility.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and male infertility, 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 “male infertility” (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: •
Varicocele: Current Concepts and Controversies Source: Current Opinion in Urology. 2(6): 463-466. December 1992. Summary: A varicocele is a dilatation of the scrotal portion of the internal spermatic venous system that drains the testicle. This article discusses current concepts and controversies surrounding the varicocele, reviewing current developments regarding the etiology, pathophysiology, diagnosis, and therapy of varicoceles. The authors stress that varicoceles are common, particularly in men being evaluated for infertility. Varicocelectomy has been reported to result in an improvement in seminal parameters, testicular size, and testicular histology. The authors conclude that despite new and sophisticated means of identifying varicoceles, assessing impaired testicular function, and treating varicoceles, several basic questions remain regarding the role of varicocele in male infertility. 22 annotated references.
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Male Infertility
Infertility and Impotence Following Renal Transplantation Source: Current Opinion in Urology. 6(2): 115-119. March 1996. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Fax (215) 574-3533. Summary: Chronic renal failure is frequently accompanied by endocrine abnormalities that may result in infertility and impotence. This review article details the etiology, evaluation, and treatment of infertility and impotence in the transplant recipient. The authors note that a better understanding of the hormonal changes accompanying endstage renal disease (ESRD) and the effects of immunosuppressive agents on those changes has improved the ability to restore sexual and reproductive function to this population. The transplant recipient should be deemed a candidate for all available modalities for the treatment of urologic disorders. This includes injection and surgical procedures for the treatment of impotence that appear to carry only a minimal, if any, increased incidence of infection. One section covers female infertility factors, but the majority of the article focuses on male infertility and impotence issues. 1 figure. 27 references. (AA-M).
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MRI for Evaluating Abnormalities of the Testes Source: Contemporary Urology. 2(7): 13-19, 22-23. September 1990. Summary: This article examines how the clinician can use magnetic resonance imagin g (MRI) to evaluate testicular abnormalities. Also discussed is the potential usefulness of P-31 magnetic resonance spectroscopy in evaluating male infertility and diagnosing testicular torsion. Conditions considered include cryptorchidism, testicular inflammatory processes, and scrotal masses. 11 figures. 21 references.
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Urology Source: Journal of the American College of Surgeons. 186(2): 241-246. February 1998. Contact: Available from Journal of the American College of Surgeons. P.O. Box 2127, Marion, OH 43306-8227. (800) 214-8489 or (740) 382-3322. Fax (740) 382-5866. Summary: This review article offers a summary of selected contributions in the disciplines of urologic oncology (cancer of the urinary tract), neurourology and voiding dysfunction, impotence (erectile dysfunction) and male infertility, urinary tract infections, and pediatric urology. Screening for prostate cancer (PSA serum tests and digital rectal examinations) is now recommended annually, beginning at age 50, and in high risk younger men (such as those with a family history of the disease). As more prostate cancers are detected in potentially curable stages, the treatment options have become more complex. The author considers the appropriateness of bladder sparing treatments for muscle invasive transitional cell carcinoma (cancer) of the bladder. Other long term followup research showed that men with testicular cancer continue to be at significant risk for second malignancies. In the area of neurourology and voiding dysfunction, the author reports on ongoing work to improve bladder function in patients with spinal cord injury. In the area of erectile dysfunction (ED), the author reports on the use of transurethral alprostadil, and sildenafil (Viagra). In the discipline of assisted reproductive technology, the past year has seen dramatic advances in the area of male infertility: it is now possible to obtain sperm from approximately 50 percent of men who had previously been labeled sterile. The author discusses the implications of using intracytoplasmic sperm injection for in vitro fertilization. 22 references.
Studies
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Complex Role of the Urologic Nurse: Balancing Scientific Knowledge and Technology with Care and Compassion Source: Family Urology. 7(3): 16-19. 2002. Contact: Available from American Foundation for Urologic Disease. 1126 North Charles Street, Baltimore, MD 21201. (800) 242-2383 or (410) 468-1800. Fax (410) 468-1808. Website: www.afud.org. Summary: Urologic nursing is a highly specialized area of nursing practice that developed in response to the increasing specialization of urologic practice and the development of new technologies for diagnosing and treating urological conditions. This article provides information to health care professionals and patients about the complex role of the urologic nurse. Urologic nurses work in homes, hospitals, clinics, doctor's offices, long-term care facilities, rehabilitation centers, and in a variety of unique settings specializing in such areas a continence care, male infertility, stone disease, and prostate cancer. The authors discuss the nature of urologic nursing as it applies to each of the seven domains of clinical nursing practice: the helping role, the teaching-coaching function, monitoring function, managing rapidly changing situations, administering and monitoring therapeutic interventions, monitoring and ensuring the quality of health care practices, and handling organization and work role competencies. The authors also include brief vignettes in each domain, related to the urologic nurse. 7 references.
Federally Funded Research on Male Infertility The U.S. Government supports a variety of research studies relating to male infertility. 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 male infertility. 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 male infertility. The following is typical of the type of information found when searching the CRISP database for male infertility: •
Project Title: AROMATASE HYPERPLASIA
INHIBITOR
IN
MALES
WITH
ADRENAL
Principal Investigator & Institution: Sarafoglou, Kyriakie; Pediatrics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006
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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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Male Infertility
Summary: (provided by applicant): Our objective is to treat males who have congenital adrenal hyperplasia (CAH) and decreased spermatogenesis with an aromatase inhibitor in order to investigate its effects on hormonal parameters and spermatogenesis. CAH is a family of inherited disorders caused by reduced activity of the enzyme required for cortisol synthesis. Decreased cortisol production increases the secretion of ACTH from the pituitary and increases the production of adrenal androgens through negative feedback. In turn, the increased levels of adrenal androgens are aromatized/converted in glandular (i.e., testes) and extraglandular tissues by the aromatase enzyme and result in elevated estrogen levels. Ideally, the production of adrenal androgens is normalized in CAH patients by glucocorticoid replacement therapy. However, even well controlled CAH patients still manifest the adverse effects (compromised final height, polycystic ovarian disease, male infertility, etc.) of elevated androgens/estrogens. Glucocorticoid therapy does not continually normalize ACTH levels because it lacks the close temporal relationship to ACTH pulses and any adrenal activity will result in greater than normal androgen (and thus estrogen) production. We hypothesize that these elevated estrogen levels affect spermatogenesis in males with CAH through the following mechanisms: (1) Elevated estrogens suppress the hypothalamic-pituitary-gonadal axis through negative feedback. Normal LH/FSH gonadotropin secretion is essential for the initiation and maintenance of testicular function and normal spermatogenesis. Chronically elevated estrogen levels (estradiol) affect testicular morphology and testicular steroidogenesis (a) by suppressing pituitary-gonadal secretion, and (b) by a direct toxic effect of estradiol on testicular tissue resulting in a decrease in testicular testosterone production, decrease number of androgen receptors, and create a further negative imbalance in the testosterone-to-estradiol ratio at the gonadal level; (2) Elevated estrogens adversely affect testicular function including Leydig cell, Sertoli cell and germ cell development as shown in experiments with rodents that have been exposed to excess estrogens; (3) Elevated estrogens cause dysfunction of the efferent ductules and epididymis. Therefore, the overarching question of our study is the following: What degree of positive effect will controlling the conversion/aromatization of elevated adrenal androgens into estrogens by gonadal tissue have on spermatogenesis in CAH males? We propose that inhibiting aromatization of androgens to estrogens with an aromatase inhibitor, will improve testicular function and spermatogenesis by normalizing the estradiol to testosterone ratio at the gonadal level and reversing the negative effects of elevated estrogen on androgen receptors, testicular steroidogenesis and pituitary gonadotropins. Aromatase inhibitors have selective action, are well tolerated by patients, and do not interfere with the production of steroid hormones by other related cytochrome P450-dependent enzymes making it ideal for use in CAH patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASIS FOR MALE INFERTILITY: MOLECULAR MODELS Principal Investigator & Institution: Pilder, Stephen H.; Associate Professor of Anatomy And; Anatomy and Cell Biology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 15-JUL-1994; Project End 30-JUN-2004 Summary: The mammalian sperm flagellum produces a regulated locomotive force that allows the sperm cell to proceed through a set of complex environments in the female genital tract and penetrate the egg investments. However, little beyond morphological description is known about the control of mammalian sperm flagellar formation, stability, or movement. The P.I. has mapped and isolated an axonemal dynein heavy chain, Dnahc8, that is expressed at high levels in a testis-specific fashion in wildtype
Studies
7
mice. The map position of Dnahc8 and its mode of expression in the testes of certain male-sterile recombinant lines of mice is completely consistent with the flagellar organization and waveform defects, known as "whipless" and "curlicue", respectively, displayed in an allele-specific manner by sperm from these recombinant mice. Thus, Dnahc8 is a strong candidate for the allele-dependent expression of the "whipless" and "curlicue" mutations. Because Dnahc8 expression appears to have profound effects on both sperm tail biogenesis and function, Dnahc8 offers a key to unraveling the mechanisms underlying mammalian sperm tail assembly and/or motility. In order to test the hypothesis that Dnahc8 is responsible for expression of "whipless" and "curlicue", and to begin to clarify the cellular mechanisms underlying these phenotypes, the P.I. will determine the subcellular location of Dnahc8 in both mutant and control testis and cauda epididymal sperm through immuno-light and electron microscopy, and isolate potential spermiogenic binding partners of Dnahc8 through two-hybrid analysis (Specific Aim I). Concurrent with the performance of Specific Aim I, the P.I. will directly test the postulated role(s) of Dnahc8 in sperm tail assembly and function via its targeted deletion from the mouse genome (Specific Aim II). In order to assess the potential significance of Dnahc8 to human male infertility, the P.I. will localize the human ortholog of Dnahc8 to a sub-chromosomal region within the human genome, and will ascertain if this ortholog demonstrates polymorphisms diagnostic of human male infertility related to sperm flagellar defects (Specific Aim III). These experiments will reveal information crucial to our understanding of the molecular basis of mammalian sperm tail development and function in fertilization, while contributing to our ability to diagnose and treat human male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGICAL ROLE OF A NOVEL TESTIS INSULIN-LIKE PROTEIN Principal Investigator & Institution: Menon, Ram K.; Professor of Pediatrics; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The proteins of the insulin family play essential roles in pleotropic physiological processes affecting metabolism, growth, and reproduction. Using the techniques of molecular and computational biology our laboratory recently identified a novel member of the insulin family we termed Insl6 (insulin-like protein 6). Expression of Insl6 is greatest in germ cells of the testis. Evolutionary conservation of the structure of the Insl6 gene suggests an essential biological role for this protein. However, at present the biological role of Insl6 is not known. Our preliminary studies have identified a subject with male infertility with a heterozygous mutation in the INSL6 gene. Our studies indicate that the identified mutation alters the intra-cellular trafficking of the Insl6 protein. Specific Aim 1 expands on these observations and tests the hypothesis that mutations in the INSL6 gene are associated with characteristic phenotypes in the human. The genotype-phenotype correlation will be established by analysis of clinical history, physical examination, sperm analysis, and endocrine profile. Specific Aim 2 tests the hypothesis that the Insl6 null phenotype, generated by targeted disruption of the murine Insl6 gene, will reflect the biological role of Insl6. The Insl6 null mice will be evaluated for phenotypic characteristics including viability, sexual differentiation, fertility, testicular macro- and microstructure, sperm analysis, and endocrine profile. The identification of new members of the insulin gene family has led to the elucidation of novel functions for this family of proteins. For example, targeted disruption of insulin-like peptide 3 (Insl3) in
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Male Infertility
the mouse revealed a critical role for this peptide in testicular descent. Furthermore, the recent discovery of the cognate receptor (LGR8) for Insl3 and the elucidation of cryptorchidism as one of components of the LGR8 null phenotype underscore the exciting advances made in this field. The results from experiments outlined in this proposal will advance our understanding of the biological role of Insl6 and provide insights into human reproduction and disorders such as infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGY OF THE TESTIS Principal Investigator & Institution: Means, Anthony R.; Nanaline H. Duke Professor and Chair; Pharmacology and Cancer Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-MAY-1977; Project End 31-MAR-2006 Summary: (Scanned from the applicant's description): The long-term objectives of the proposed research are to elucidate how calcium/calmodulin-dependent protein kinase IV (CaMKIV) participates in calcium/calmodulin (Ca2+/CaM)-mediated signal transduction cascades and regulates the cells in which it is expressed. Mice have been generated that are deficient in CaMKIV, its upstream activating kinase CaMKK beta or its alternate gene product calspermin. Camk4-/- mice are male (and female) infertile, unable to mount a type 2 immune response and exhibit profound loss of coordination and motor control. The specific defect in male infertility involves a disappearance of the protamine 2 precursor in step 15 spermatids and is similar to a defect identified in a subset of infertile human males. The immunological defects arise due to the inability to produce IL-4 in naive CD4+ T cells and, thus, are reminiscent of those identified in allergic asthma. Finally, the survival of thymocytes and cerebellar Purkinje cells is decreased in the Camk4-/- mice in a manner that may be related to transcription of genes regulated by orphan receptors of the ROR family. It is proposed to examine the molecular events in naive CD4+ T cells and thymocytes that require CaMKIV (or CaMKK beta) using transcription of IL-4 and transcription by ROR as endpoints. This will be accomplished using a combination of molecular/biochemical, functional genomic and proteomic technology. This research will define the phosphoproteome of the naive CD4+ T cell and identify the genes in thymocytes that require ROR for expression. In addition the research will determine the role for calspermin in spermiogenesis and ovulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: FUNCTION
BMP
SIGNALING
IN
EPIDIDYMIS
DEVELOPMENT
AND
Principal Investigator & Institution: Zhao, Guang-Quan; Pharmacology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 05-JUN-2000; Project End 31-MAY-2005 Summary: Bone Morphogenetic Proteins (BMPs) are multi-functional regulators of development and differentiation. They exert their functions by regulating cell fate, proliferation, differentiation, and survival. Our preliminary results have shown that several murine genes encoding BMPs (Bmp4, Bmp7, and Bmp8a), BMP receptors (Alk3, Alk6, and Talk), and a downstream signal transducer (Smad1) are expressed in the developing and adult epididymides. Furthermore, mutations in Bmp8a and Bmp8b lead to vacuole formation in the epididymal epithelium, granuloma formation, and male infertility. These data support a hypothesis that multiple genes of the BMP signaling pathways have overlapping roles in controlling the development and functions of the
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epididymis. The goal of this application is to test the hypothesis by a combination of sophisticated genetics approaches and retrovirus-mediated gene transfers. Specific Aim 1 is designed to further investigate the roles of BMP signaling components (Bmp7, Alk3, and Smad1) and the testis-derived BMPs is the functional maintenance of the adult epididymides. In this aim, the functions of Bmp7 will be studied by creating double mutants with Bmp8a and by further examining the severity of the epididymal defects in these double mutants. Furthermore, the regulation of Bmp7 expression during postnatal epidiymis development by testicular factors and androgens will be investigated as part of our long-term goal to dissect the molecular mechanisms controlling the growth and development of the epididymis. A transgenic over-expression of Bmp8a in the male germ cells will be used to further reveal the functions of testis-derived BMPs in the maintenance of the adult epididymus. The roles of Alk3 and Smad1 in mid- to distal epididymides will be investigated by the Cre/lox recombination system. In Specific Aim 2, the roles of BMP signaling components in postnatal epididymis development will be investigated. Bmp7 null mutants and Bmp7/Bmp4 double mutants will be used to address the roles of these genes in the development of early postnatal epididymides. Moreover, a retrovirus vector, RCAS-Cre, will be used to inactivate Alk3 and Smad1 in the development of mid-pubertal epididymides. The results obtained from these investigations will add significantly to our understanding of the molecular mechanisms controlling the epididymis development and functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARNITINE PALMITOYLTRANSFERASE I AND THE GERM CELL Principal Investigator & Institution: Esser, Victoria; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 04-MAR-2002; Project End 28-FEB-2005 Summary: The mitochondrial oxidation of long chain fatty acids is regulated in large part at the level of carnitine palmitoyltransferase I (CPT I) located on the mitochondrial outer membrane. This enzyme exists in at least two isoforms, the liver (L) and muscle (M) types, which are expressed to different extents in any given tissue. We have recently discovered that the M-CPT I gene is robustly expressed in the testis of the rat, mouse and human. More specifically, we have shown that the production of M-CPT I mRNA and protein is restricted to the developing germ cell at the early meiotic stage of development, whereas non-germ cells of the testis express only L-CPT I. By contrast, in the ovary, L-CPT I mRNA is abundant while the M-CPT I gene remains dormant. Because the role of fatty acid oxidation in general, and of CPT I in particular, in germ cell development and function have received little if any attention to date we would like to try to break through this impasse. Accordingly, we have two specific aims. First, to create a mouse line in which the M-CPT I gene has been disrupted selectively in developing sperm (using the Cre/loxP technology) and to determine the effect of the knockout on the animal's ability to transmit the mutant gene to progeny. The possible impact of this transmission on heart and skeletal muscle function will also be examined. Second, to determine which cell types in the testis and ovary express L-CPT I using the techniques of in situ hybridization, immunocytochemistry and biochemical analysis. If, as we suspect, M-CPT I turns out to be crucial for normal sperm development, we will determine if spermatocytes lacking the enzyme progress to a non-functional spermatozoan stage or become arrested earlier in development. If the latter, a detailed phenotypic analysis of the abnormal germ cells will be performed. Such information would fill a major gap in our understanding of sperm physiology and could become relevant to the issue of male infertility, most cases of which have defied explanation to
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date. It would also throw light on whether we are ever likely to find cases of inherited human M-CPT I deficiency (none have been reported to date) and, if so, whether the faulty gene can be passed through the male germ line. Finally, should CPT I prove to be important in germ cell function, important questions would be raised concerning the proposed use of CPT I inhibitors in the treatment of diabetes and postischemic heart injury. On the other hand, a reversible CPT I inhibitor that could be targeted to the testis or ovary might well find use as a male or female contraceptive agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL-CELL INTERACTIONS IN TESTIS DEVELOPMENT Principal Investigator & Institution: Skinner, Michael K.; Professor; School/Molecular Biosciences; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The proposed research is designed to develop a better understanding of the mechanisms that control and maintain testis development and function. Of particular interest are the cell-cell interactions that regulate testis growth, size, and morphogenesis which directly influence male fertility and sperm production. Preliminary research has demonstrated that two families of paracrine growth factors directly influence testis development and function. The general hypothesis examined is that locally produced paracrine growth factors are essential for cell growth and differentiation during embryonic and postnatal testis development and that this directly influences male fertility and sperm production in the adult. Abnormal testis development and male infertility may in part be due to inappropriate control of testicular cell growth and differentiation during development. The specific hypothesis tested is that subsequent to genetic male sex determination (e.g. sry) precursor Sertoli cells produce neurotropins (e.g. nt3) that act as a chemotactic agent for specialized cells in the mesonephros to migrate into the developing testis and develop into precursor peritubular cells that produce growth factors (e.g. hepatocyte growth factor) to promote seminiferous cord formation from aggregates of Sertoli and primordial germ cells, and that following this morphological testis differentiation (i.e. cord formation) that transforming growth factors (i.e. TGFb) are induced by similar locally produced growth factors to regulate the rapid cell growth and cell survival associated with embryonic testis development. Preliminary studies indicate that the transforming growth factor family is critical for embryonic testis growth. Preliminary studies also indicate that the neurotropin family of factors (e.g., NT3) has a critical role in the morphogenesis of testis development (i.e., sex cord or seminiferous tubule formation). Both growth factor families have been demonstrated to influence germ cell development and survival. This non-neuronal action of the neurotropins when blocked inhibited normal testis development and morphogenesis. Further analysis of these phenomena and the experimental approach consists of the following specific aims: 1. investigate the role of the neurotropin growth factor family in testis development, 2. investigate the role of the transforming growth factor- beta family in testis development. 3. investigate the physiological function of these growth factors during testis development on male fertility. The completion of these studies will provide insight into the cell-cell interactions and factors that control embryonic testis growth and function. Testicular cell (e.g., Sertoli) growth and differentiation is essential for embryonic, prepubertal, pubertal, and adult testis function. Abnormal control of these cell-cell interactions is anticipated to result in male infertility. Inappropriate expression of the growth factors or receptors may result in subfertile males. Addition of these factors may enhance and improve male fertility. Therefore, observations from the current proposal will provide a
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better understanding of normal and abnormal testis development and function. It is anticipated that the observations will lead to the design of future: therapeutic treatments for male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTROSOME DEFECTS AS CAUSES OF MALE INFERTILITY Principal Investigator & Institution: Schatten, Gerald P.; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Flawless sperm functioning is essential for the successful completion of fertilization in humans. This functioning includes activities of the sperm prior to its meeting the oocyte, sperm-oocyte plasma membrane fusion, and the cytoplasmic events mediated by the sperm nucleus and centrosome that conclude the fertilization processCthe merging of the parental genomes in the activated zygote. Defects in sperm behavior at any stage result in the inability to complete fertilization, and quantitative analyses of these defects have been developed into assays for male infertility. These assays determine the extent of aberrations in sperm number, morphology, motility, the ability to undergo the acrosome reaction, the release of acrosome enzymes, and penetration assays into zona-free hamster oocytes or isolated zonae. This application investigating idiopathic male infertility studies the microtubule organizing capacity of the human sperm centrosome. To investigate the exte nt t o which defects in the human sperm centrosome are causes of male infertility, questions are posed in four specific aims using sperm from fertile and infertile men. Aim #1 Is centrin, a centrosomal protein, found in human sperm, and does its concentration vary predictably in sperm donated from men of differing fertility? Aim #2. Does the binding of maternal centrosomal proteins, especially ?-tubulin, vary predictably in sperm from men of differing fertility? Aim #3. Are there differences in the ability of sperm from men with varying fertility to nucleate and direct the assembly of microtubule-containing asters in extracts from Xenopus eggs? Aim #4. Will the sperm asters formed in pronucleate-stage mammalian oocytes, inseminated with sperm from men of varying fertility, predictably vary in their size and microtubule density? FUNDING NIH R01 HD32887, HD18185 PUBLICATIONS Schatten G, Hewitson L, Simerly C, Sutovsky P, Huszar G. Cell and molecular biological challenges of ICSI A.R.T. before science? J Law Med Ethics 26:29-37, 1998. Luetjens CM, Payne CJ, Schatten G. Are chromosomes in sperm nuclei nonrandomly positioned? J Reprod Fertil 22:82, 1998. Hewitson L, Simerly C, Sutovsky P, Dominko T, Schatten G. Molecular reconstitution and inheritance of the centrosome during fertilization Implications for fertility. In Gametes Development and Function (A Lauria, F Gandolfi, G Enne, L Gianaroli, eds). Serono Symposia, pp 371-392, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION OF FLAGELLAR PROTEINS INVOLVED IN SPER* Principal Investigator & Institution: Sapiro, Rossana; University of the Republic 1824 Av 18 De Julio Montevideo, Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant) Sperm must have purposeful forward motion following deposition in the female reproductive tract in order to fertilize ovulated eggs. The factors that control the sperm flagellar power stroke and waveform are poorly understood. Spag6, a protein containing eight armadillo repeats, a protein interaction
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motife, is the murine orthologue of Chlamydomonas PF16, a central apparatus protein required for algae flagellar function. Mice lacking Spag6 are infertile due to a severe sperm motility defect, resulting in part from disruption of the flagellar axoneme architecture. This model will be used to identify proteins that interact with Spag6 and thus expand the catalogue of the mammalian axonemal proteins that are essential for flagellar structure and function. Using two dimensional gel electrophoresis and surfaceenhanced laser desorption/ionization mass spectrometry, the proteome of Spag6deficient sperm will be characterized and compared with wild-type mouse sperm to identify missing proteins. The missing proteins will be characterized and their cDNAs cloned for further documentation of interaction with Spag6 using yeast two-hybrid and pull-down assays and immunocytochemical co-localization. The domains of Spag6 that mediate protein-protein interactions will be defined using yeast two-hybrid and other assays. The proteome of human sperm with motility and ultrastructural defects that mirror those of the Spag6-deficient mouse will be examined to screen for humans with SPAG6 deficiency. The knowledge gained from this research will provide a molecular framework for understanding sperm motility defects that cause male infertility and possibly offer new avenues for contraception through the disruption of purposeful sperm motion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONSEQUENCES OF MALE LH RECEPTOR GENE KNOCKOUT Principal Investigator & Institution: Lei, Zhenmin; Obstetrics and Gynecology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 13-APR-2001; Project End 31-MAR-2004 Summary: (Provided by the Applicant) We recently succeeded in creating mice with the luteinizing hormone receptor gene knockout (LHRKO) by a homologous DNA recombination technology. Targeting deletion of the LHR gene at the promoter to exon one region completely inactivated the gene, which resulted in no detectable LHR in the gonads of homozygous animals. The LHR null males are not lethal but sterile, while their heterozygous littermates appear to be normal. The external and internal genitalia of homozygous males were grossly underdeveloped and spermatogenesis was arrested at the spermatocytes. The phenotype is believed to be caused by decreased androgen influence in the absence of LH stimulation of testicular Leydig cells. Testosterone replacement therapy, in spite of improvement in testicular morphology and spermatogenesis, did not restore male fertility, as homozygous males have very low sperm numbers and motility. In view of the fact that LH has pervasive actions, mediated by its receptors in gonadal and nongonadal tissues such as functional LHR in sperm and epididymis and with preliminary results obtained from LHRKO males, we hypothesize that the contribution of LH to spermatogenesis may be more than just acts on Leydig cells for androgen production. Having this unique LHRKO mouse model enables us to selectively investigate the crucial roles of LH in reproductive biology. This proposed research is aimed at searching for potential causes of infertility in LHRKO males even after androgen replacement therapy. Therefore, this small grant application will only focus on two aspects that are known to be critical in spermatogenesis and sperm maturation, listed as two specific aims: 1) investigating the effect of LHRKO on spermatogenic cells. 2) determining the effect of LHRKO on sperm maturation. These functional data are essential for us to further investigate the vital role of LH in male reproduction at biochemical and molecular levels. Infertility in human due to genetic defects in LHR or LH-p subunit are increasingly recognized, but there are no naturally occurring animal models with the corresponding mutations available for study. Thus,
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the data obtained from these LHRKO mice will not only advance our understanding on how important the actions of LH are for normal male reproductive physiology but will also facilitate developing better diagnostic and therapeutic options for male infertility and, conversely, developing more effective and safer male contraceptive reagents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONSTITUTIVELY ACTIVE LH RECEPTORS IN TRANSGENIC MICE Principal Investigator & Institution: Narayan, Prema; Biochem and Molecular Biology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-DEC-2007 Summary: (provided by applicant): The long-term goals of this research are to understand the reproductive consequences of expression of constitutively active luteinizing hormone receptors (LHR). The critical role of LHR in male and female reproduction is underscored by the developmental and reproductive defects resulting from activating and inactivating mutations in the receptor. For example, activating mutations in human LHR are associated with familial male-limited precocious puberty (FMPP) and Leydig cell hyperplasia. Transgenic and knockout mouse models have facilitated our understanding of normal and pathophysiological functions of hormones and receptors. To examine the consequences of chronic ligand-mediated LHR activity, we have generated transgenic mice expressing a yoked hormone-receptor fusion protein (YHR) with constitutive activity. Male transgenic mice produce increased prepubertal levels of testosterone, accompanied by decreased testicular size and diameter of the seminiferous tubules. Female transgenic mice exhibit increased folliculogenesis at early ages, and at three months there is increased follicular atresia and the presence of follicular cysts suggesting that constitutive LHR activity may result in premature ovarian failure. The goals of this proposal are to elucidate the endocrine and molecular basis for altered testicular development and early reproductive senescence observed in the ovary. In the first aim we will examine the developmental changes in testicular and ovarian morphology and histology and determine the effect of chronic LHR activation on testicular somatic cell development and oocyte depletion. In the second aim we will analyze the temporal changes in hormone levels and expression of key molecules in the LHR signaling pathways to determine the endocrine and molecular basis of the testicular and ovarian phenotype. These studies will contribute new information on testicular and ovarian physiology and pathophysiology and provide insight into the molecular mechanisms of FMPP, female infertility and premature ovarian failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROL OF PROSTATE-SPECIFIC GENE EXPRESSION Principal Investigator & Institution: Matusik, Robert J.; Director of Urologic Research; Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAY-2003 Summary: With the approach of adulthood, the prostate undergoes a developmental change that results in the maturation of that gland at puberty. At this stage, the prostate becomes a differentiated gland which produces proteins fundamental for reproduction and survival of the species. Two recent population trends place the understanding of these processes at the forefront. A decline in male fertility requires a better understanding of normal, reproductive development and an increasing aging population demands a better understanding of the further stages of prostatic growth
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that often leads to benign prostatic hyperplasia and/or prostate cancer. Androgen plays a key role in the normal development of the prostate however, little is known about the other basic molecular events that are required for organ determination and cell differentiation of the prostate. We have shown that an extremely small probasin promoter fragment contains the necessary regulatory information to target both developmental and prostatic epithelial-specific gene expression to the prostate of transgenic mice. Our hypothesis is that these PB DNA sequences can be used to identify the critical gene regulatory proteins that govern prostatic epithelial cell-specific gene expression. We believe that identifying these critical regulatory proteins which control prostate-specific gene expression will elucidate the mechanisms that control both cell determination and cell differentiation of the prostate. To decipher the information within this PB DNA fragment, the following specific Aims are planned: 1) to characterize the ontogeny of prostate-specific probasin gene expression in the developing mouse UGS; 2) to identify the PB promoter sequences that dictate prostatespecific gene expression; 3) to clone the regulatory factors that interact with the prostatespecific sequences; and 4) to determine the patterns of expression of these prostatespecific factors in the developing mouse. The ultimate goal is to provide a basic understanding of prostatic epithelial cell gene expression that will lead to insight in male infertility and the mechanism that lead to prostatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COOPERATIVE MULTI CENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Myers, Evan R.; Associate Professor; Obstetrics and Gynecology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 10-MAR-2000; Project End 28-FEB-2005 Summary: Disorders of the reproductive system, such as male and female infertility, leiomyomata, endometriosis, polycystic ovarian syndrome, and sexual dysfunction, have a major public health and economic impact. For some conditions, such as infertility, many patients are responsible for all costs associated with therapy, and unintended consequences, such as multiple gestations, are relatively common. For other conditions, such as endometriosis or leiomyomata, definitive therapy may result in the loss of childbearing potential, and long-term evidence about alternatives is scant. Relatively few interventions for these disorders have subjected to rigorous scientific evaluation. The long-term objective of this project is to improve the care of men and women with disorders affecting the reproductive system by conducting controlled trials of selected diagnostic and therapeutic interventions. The specific aims of the Data Coordinating Center (DCC) for the Cooperative Reproductive Medicine Network are (A) to develop trial protocols that address important clinical problems using scientifically valid, clinically feasible, and economically reasonable approaches through collaboration with participating Reproductive Medicine Units (RMUs) and NICHD staff, (B) to provide leadership in defining and measuring a range of important outcomes, including physiological measurements, clinical outcomes, and economic and quality of life measures, (C) to coordinate and/or provide all services necessary for conducting trials, including recruiting services, and quality control, and (D) to coordinate the analysis, reporting, and dissemination of trial results to the Data Safety and Monitoring Committee, the RMUs, NICHD, peer-reviewed journals, and the public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Coutifaris, Christos; Associate Professor and Director; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Through this application, the University of Pennsylvania seeks to continue its participation in the network of clinical reproductive medicine units (RMU). The University has established strength in clinical and basic research in infertility, endocrinology and reproductive biology. High volume clinical programs in the surgical and medical treatment of female and male infertility have been in place for over three decades. Laboratories dedicated to reproductive medicine (assisted reproductive technologies, andrology, and reproductive endocrinology) and an NIH-supported Clinical Research Center enhance the clinical and research programs. The participating faculty brings expertise in gynecology, andrology, psychiatry, clinical epidemiology and biostatistics, clinical chemistry and computer and information technology. The proposed administrative structure for the RMU includes a Principal Investigator, Christos Coutifaris, M.D., Ph.D., Director of the Division of Reproductive Endocrinology and Infertility, who will be assisted by two co- principal investigators Luigi Mastroianni, Jr., M.D., previous director of the division and original P.I. of the Penn RMU and Kurt Barnhart, M.D., M.S.C.E., director of the division's clinical research unit. In addition, an Executive Committee will oversee the progress and functions of the RMU. During the previous period of funding, the first two clinical trials were completed and the initial analysis of the superovulation/intrauterine insemination (SO/IUI) protocol was published in the New England Journal of Medicine. Analyses of the fertile male study results and those of a number of ancillary studies stemming from the SO/IUI trial are currently being performed. If funding is extended, the University of Pennsylvania RMU will continue to recruit patients for the endometrial biopsy study (Penn's "concept protocol" in the previous submission) recently approved as a Network-wide protocol and will participate in any new studies decided upon by the steering committee and NICHD. It is anticipated that two additional years will be required for completion of the endometrial biopsy study. It is also anticipated that the protocol for the use of Methotrexate for treatment of ectopic pregnancy will be implemented in all RMN sites. With the recent establishment of a clinical research unit within the Division, which has dedicated space, equipment and personnel, the Penn RMU is in the unique position to undertake and successfully participate in multiple concurrent clinical trials. It is our expectation that as the Reproductive Medicine Network has now matured, multiple protocols will successfully be implemented. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Diamond, Michael P.; Professor; Obstetrics and Gynecology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 30-JUN-2000; Project End 31-MAR-2005 Summary: Our overall goal is to improve the reproductive health of men and women, thereby fostering the birth of healthy and wanted children. The objective of this application is to become part of the Cooperative Multicenter Reproductive Medicine Network (CMRMN). We are committed to cooperative research and offer a large patient
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base (including an unusually high percentage of minorities) from which to enroll subjects into Network protocols. We propose to achieve this objective by documenting that Wayne State's spectrum of research expertise and resources is consistent with successful participation in the Network; by providing evidence of Wayne State's commitment and track record in cooperative clinical research; and by providing a 'concept' protocol as proof of our ability to conceive and design a cooperative project. It is our expectation that we would be an integral and contributing member of the CMRMN in research identified by other members, and as an innovator of new projects. In particular, we would contribute to genome-wide screening for genetic differences that could explain the pathogenesis of reproductive abnormalities. One of our longrange research goals is to identify congenital and acquired genetic causes of male infertility, so that highly specific counseling and/or therapy can be offered to affected couples considering assisted reproductive technologies as a solution to infertility. The specific objective of our concept protocol is to identify genes, through the innovative application of microarray technology, closely associated with male factor infertility. The central hypothesis for the proposed research is that gene transcripts (mRNA species) contained in the sperm of infertile males will differ qualitatively and quantitatively, compared to those of fertile men, thereby allowing candidates for 'infertility genes' to be identified. The rationale is that once candidate genes have been identified by cooperative genome-wide screening, hypothesis-driven research can be formulated to determine whether they relate casually to one or more genetic forms of male factor infertility. We will test our central hypothesis by pursuing two specific aims: 1) identify the extent to which the profile of gene transcripts varies in the sperm of fertile males; and 2) identify gene transcripts that are expressed differently in the sperm of infertile, compared to fertile, men. The CMRMN is vital to successful completion of the protocol; it will assure the power needed to interpret results accurately. The proposed translational research is innovative because it combines clinical and basic molecular genetic expertise in a cooperative effort that will employ new analytical (microarray) technology to cost- effectively obtain clues to the genetic causes of male factor infertility. The outcomes will be significant because they will provide the foundations for definitive analysis of genetic factors that negatively affect male fertility, thereby leading to highly accurate, inexpensive diagnostic tests for genetic causes of male factor infertility, and in some cases, allow the prescription of specific replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--PATIENT/BIOSTATISTICS FACILITY Principal Investigator & Institution: Corey, Mary; Associate Professor; Hospital for Sick Chldrn (Toronto) 555 University Ave Toronto, Timing: Fiscal Year 2002 Summary: The Patient/Biostatistics Core provides an overall structure for maintaining and connecting all the available patient data related to mutations in the CFTR gene, generates regular summaries for the design and analysis of experiments and observational studies. Core activities will include: integration of new clinical and scientific data into the Toronto CF Database; support for the database on male infertility patients, who comprise the largest identified group of an expanded spectrum of patients affected by mutations in the CFTR gene; creation of data files and analytic strategies to study other atypical phenotypic groups related to CFTR, such as young patients with pancreatitis and adults with chronic lung disease; provision of clinical profiles for individual patients and patient groups to enhance the planning or interpretation of scientific experiments; statistical analysis of core and project data; and timely statistical
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consulting for the design and interpretation of experiments. A particular focus in the next period will be the acquisition and support of new and developing software for linkage and association analysis of complex genetic traits. SAS software is used for most data management and statistical analysis, including longitudinal regression and survival regression. Other computer programs used for specific purposes include SPLUS (for graphics and sophisticated statistical estimation); Mapmaker/Sibs, SAGE, and GAP (for genetic linkage and association analysis); DBMS/COPY and ConversionsPlus for converting and transferring files between different systems. Increasingly, different types of laboratory data will be retrieved directly from other computer systems within the hospitals, necessitating increased levels of quality control and validity checking to ensure appropriate record linkage and to preserve the confidentiality of identified patient data. Core support will ensure that scientists have access to the most appropriate patient information and material to design experiments, and that research hypotheses and results are related as immediately and precisely as possible to patient data, to define the links between mutations, protein dysfunction, and disease expression. This core encourages collaboration of basic and clinical investigators, and therefore hastens the application of new knowledge to patient management and treatment evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA-PROTEIN INTERACTIONS IN SPERM CHROMATIN Principal Investigator & Institution: Brewer, Laurence R.; Electronics Engineering; University of Calif-Lawrnc Lvrmr Nat Lab Lawrence Livermore National Lab Livermore, Ca 94550 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Dr. Brewer is a physicist with a background in laser cooling and trapping of atoms, atomic spectroscopy and optical science, who has recently started to experimentally study the condensation of single, optically trapped, DNA molecules by proteins. These experiments have been pursued in collaboration with a structural biologist at Lawrence Livermore National Laboratory (LLNL) - Dr. Rod Balhorn - and have been carried out in Dr. Brewer's laboratory at LLNL. While this collaboration has been successful, and recently resulted in publications in various journals, including Science, Dr. Brewer has not been able to propose which research questions to pursue because of his lack of a fundamental knowledge of biology. While he is adept at building optical traps and imaging single DNA molecules, he is in large part dependent on Dr. Balhorn for determining which direction the research should take. Dr. Brewer's immediate objective is to gain the necessary biology knowledge to both understand, and propose questions in the field he is studying - the structural biology of mammalian gamete cell- and his long term career goal is to become an independent researcher in the field of biomedicine, applying experimental physics techniques to study biological questions. His career development plan is to take courses in the Molecular and Cellular Biology department at U.C. Berkeley for two years, learn laboratory protocols and techniques relevant to his proposed research from Dr. Balhorn's group, and simultaneously pursue experiments in his own laboratory, in collaboration and consultation with his proposed mentor, Dr. Balhorn. The research proposed is to study the sequence of proteins that condense DNA in the developing mammalian sperm cell and decondense it following fertilization. An individual, optically trapped DNA molecule will be moved sequentially through the proteins in a novel multichannel flow cell, and structural changes in the molecule will be observed by fluorescence microscopy. The proteins include the transition proteins TP1 and TP2, the condensing
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proteins, protamine 1 and 2, and the decondensing protein nucleoplasmin. The results of this research have a direct bearing on understanding male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF ORGANOCHLORINES ON MALE INFERTILITY Principal Investigator & Institution: Wirth, Julia J.; Epidemiology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 09-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Ten to 17% of American couples currently seek medical help for infertility; half of these problems have a male cause usually of unknown etiology. Wildlife, experimental animal and human epidemiological studies indicate that environmental contaminants, especially organochlorine compounds (OCs) such as polychlorinated biphenyls (PCBs) and OC pesticides have adverse effects on male reproduction. To investigate the relationship between measure of human male reproductive health, specifically semen quality and reproductive hormone levels (FSH, LH, testosterone and inhibin B, considered to be the best available endocrine marker of spermatogenesis), OC environmental contaminants and polymorphisms in genes involved in contaminant and sex steroid metabolism (P450), we propose to conduct a case-control study recruiting subjects based on sperm density from an infertility in Detroit, Michigan. Cases will be men with low sperm densities (less than 2 x10x6/ml), and controls (2 groups) will be men with sperm densities greater than 2 but less than 20x10x6/ml, and men with normal sperm densities (greater than 20x10x6/ml). Information on Great Lakes sport-caught fish consumption, as well as on other risk factors will be obtained from a self-administered questionnaire. Secondary exposures (contaminants present in Great Lakes fish), including PCBs and OC pesticides will be measured from a blood sample. P450 polymorphisms will be measured in buccal (cheek) cell DNA. This adequately powered case-control study of men with low sperm densities from an area of the Great Lakes with both known OC contamination and a significant percentage of anglers will provide data that will help determine if consumption of Great Lakes sports-caught fish has or does not have adverse effects on measures of male reproductive health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF OXIDATIVE STRESS ON HUMAN SPERM DNA Principal Investigator & Institution: Sawyer, Dennis E.; University of Newcastle 2308, New South Wales Newcastle, Timing: Fiscal Year 2002; Project Start 08-JAN-2002 Summary: The primary goal of this study is to determine if mitochondrial DNA in human sperm is more sensitive to oxidative damage than nuclear DNA. The long-term goals of this research are to further our understanding of role of oxidative stress in human male infertility, and ultimately, to establish a link between oxidative damage in male germ cells, germ-line mutagenesis, and birth defects. Recent research on etiology of male infertility indicates that oxidative stress is a primary cause for sperm dysfunction. Excessive ROS production by spermatozoa has been associated with abnormal semen profiles, and results in loss of motility, lipid peroxidation, and DNA damage. However, effects of oxidative stress on sperm mitochondrial DNA has not been examined. Mitochondrial DNA of somatic cells is known to be more sensitive to oxidative damage than nuclear DNA. The experiments in this proposal will determine if the same is true in human sperm. If so, mitochondrial DNA may serve as a sensitive biomarker for DNA
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damage in human sperm. In separate experiments, human sperms ill be exposed to oxidative stress by treatment with hydrogen peroxide, the H2O2 generating system glucose/glucose oxidase, 4-hydroxynonenal, activated leukocytes, and NADPH (which causes increased ROS production by sperm). After treatment, total DNA from sperm will be isolated, and subjected to a quantitative PCR assay. Using this assay, gene- and mitochondria-specific DNA damage will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENVIRONMENTAL AUTOREGULATION
ANTI-ANDROGENS
AND
AR
Principal Investigator & Institution: Yang, Eddy S.; Molecular and Cellular Pharm; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-APR-2002 Summary: Androgen receptors (ARs) play an important role in regulating the expression of genes necessary for normal development of the male urogenital tract and for the maintenance of reproductive function. AR functions as a ligand-activated transcription factor and has been implicated in a number of human pathologies, most notably prostate cancer. AR also undergoes autoregulation, a process by which androgens regulate AR mRNA transcription and AR protein stability. This action may be a mechanism by which cells can alter their responsiveness to androgens. My sponsor and others have shown that AR mRNA levels may correlate with androgen sensitivity. Industrial chemicals and the so-called "environmental endocrine disruptors" may interfere with androgen-mediated activities. The increasing incidence of human male genital tract malformations, male infertility, and female breast cancer may be due in part to antiandrogenic effects of these compounds. Studies suggest that two such chemicals, DDE (a metabolite of the pesticide DDT) and M2 (a metabolite of the fungicide vinclozolin) inhibit AR DNA-binding and the subsequent transactivation of target genes. Also, other laboratories have found that these chemicals may possess agonist activities, especially at high concentrations. This proposal seeks to assess the effects of DDE and M2 on AR autoregulation as well as the effects of pre-exposure to these chemicals on cellular responsiveness to androgen. Two different models of androgen target tissues, LNCap (prostate cancer) and T47D (breast cancer), will be used for these studies. Our long- term goal is to elucidate the mechanisms by which these environmental antiandrogens affect AR autoregulation and responsiveness and how these effects may be associated with detrimental and developmental pathologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENVIRONMENTAL TESTICULAR TOXICITY & GERM CELL APOPTOSIS Principal Investigator & Institution: Richburg, John H.; Assistant Professor; Pharmacology and Toxicology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-JUL-1997; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): The focus of this research project is on the mechanisms responsible for initiating testicular germ cells to undergo apoptosis after toxicant-induced Sertoli cell injury. Recent evidence suggests that exposure to environmental toxicants (organic chemicals, metals, and heat) is responsible for a decline in semen quality in men over the Last 50 years. However, despite this association of toxicant exposure and male infertility, Little is known of the mechanisms
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by which these agents cause a loss of germ cells. In this research project, the investigators will use mono-(2-ethyLhexyL) phthalate (MEHP), a widely characterized Sertoli cell toxicant, as our primary model agent to study the mechanisms initiating germ cells to undergo apoptosis. In the previous grant-funding period the investigators established that the Fas (CD95)- signaling pathway participates in the initiation of testicular germ cell apoptosis after MEHP-induced Sertoli cell injury. Recently, they made two exciting and critical observations: 1) The re-distribution of Fas in germ cell changes from a cytosolic to a membrane localization after MEHP exposure and, 2) young gld mice, that lack a functional form of FasL, are not sensitive to MEHP-induced apoptosis whereas adult gld mice are sensitive. These fundamental observations have led to the development of two working hypotheses. 1) Fas plays the dominant role in the initiation of MEHP- induced germ cell apoptosis, and, 2) p53 activation leads to the expression of Fas on the germ cell membrane and confers its sensitivity to apoptosis. The first specific aim of this proposal utilizes mutant mice that express either dysfunctional Fas (lpr mice) or FasL (gld mice) to directly examine the dependence of MEHP-mediated germ cell apoptosis on the cellular expression of Fas. In the second aim, the involvement of p53 in mediating the membrane distribution of Fas is tested both in vitro, using GC-2spd cells that express a temperature sensitive mutant of p53, or in vivo, using p53 null mice. In the Last two aims, the two hypotheses are further challenged by evaluating both the importance of the soluble form of FasL and the participation of alternative Fas-independent signaling mechanisms in the pathogenesis of MEHP-induced increases in germ cell apoptosis. This investigation of MEHPstimulated germ cell apoptosis will provide fundamental insights into mechanisms regulating the sensitivity of germ cell to undergo apoptosis after chemical-induced testicular injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENVIRONMENTAL/INDUSTRIAL TOXICANTS AND TESTICULAR INJURY Principal Investigator & Institution: Boekelheide, Kim; Professor; Pathology and Lab Medicine; Brown University Providence, Ri 02912 Timing: Fiscal Year 2002; Project Start 27-SEP-1985; Project End 30-APR-2004 Summary: (Adapted from the Investigator's Abstract) While controversial, reports of a dramatic decrease in human sperm counts due to exposure to environmental toxicants are alarming. All agree that infertility is common, affecting one out of every eight couples, and that male dysfunction accounts for half of this incidence. "Irreversible" testicular injury is a form of male infertility in which proliferating germ cells fail to repopulate the testis because they die prematurely by programmed cell death (apoptosis). 2,5-Hexanedione is an environmental toxicant that produces irreversible testicular injury in the rat. After a decade of investigation, this rat model is sufficiently well characterized to study the underlying mechanisms of testicular failure in irreversible injury. Two recent discoveries have primed this research area for a major advance. First, the apoptosis-inducing Fas system, with Sertoli cells expressing Fas ligand and germ cells expressing Fas receptor, has been identified as a key regulator of germ cell survival. This new appreciation for the role of apoptosis in modulating germ cell homeostasis, when combined with the known importance of growth factors like stern cell factor, leads to the following working hypothesis: the failure of germ cell survival in toxicant-induced irreversible testicular injury is explained by a disruption in the balance between growth factor support and death-inducing factors in the local paracrine environment. Second, irreversible injury can be rescued by lowering the
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intratesticular testosterone concentration with leuprolide. Three Specific Aims are designed to exploit this new information as follows: 1) using the Fas ligand deficient gld mutant mouse and p53 knockout mouse, identify the signal and execution elements which modulate germ cell apoptosis, 2) follow the expression of growth and death factors during leuprolide- induced rescue, and 3) test specific targets of irreversible injury by delivering adenovirus expressing transmembrane stem cell factor and by infusing caspase inhibitors with Alzet minipumps. Together, these complimentary approaches will elucidate the key molecular mechanisms responsible for irreversible testicular injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF MALE INFERTILITY--CRYPTORCHIDISM Principal Investigator & Institution: Lee, Peter A.; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: Paternity in formerly cryptorchid men is being analyzed in relation to age of orchiopexy, size and location of testes before orchiopexy, duration of attempted conception and unilateral or bilateral involvement. Gonadotropin levels before and after GnRH stimulation, plasma testosterone levels and semen analyses are being compared among men in unilateral and bilateral fertile and infertile plus control groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDIDYMAL MATURATION OF SPERM SIGNALING PATHWAYS Principal Investigator & Institution: Gerton, George L.; Research Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: The long-term goals of the Principal Investigator and the Foreign Collaborator are to understand the molecular basis of sperm fertilization competence. The PI has focused in his research on the signal transduction mechanisms underlying sperm capacitation, which requires a maturation process that occurs during their transit through the epididymis. The foreign investigator has studied the biochemistry and cell biology of epididymal maturation. Together, these investigators have demonstrated an apparent maturation of the signal transduction mechanisms in parallel with epididymal maturation. The aims of this proposal are to 1) determine whether sperm epididymal transit is associated with alteration of cholesterol efflux in response to serum albumin and beta cyclodextrins, agents that bind cholesterol in vitro, 2) determine the mechanisms by which epididymal maturation regulates the response of the sperm to dbcAMP leading to protein tyrosine phosphorylation, and 3) determine whether the oxidation state of the epididymal environment can influence the maturation of the signal transduction machinery that regulates sperm capacitation. The results of these experiments may aid in the understanding of epididymal maturation and its role in fertilization competence, which may relevant to both male infertility and contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPISTASIS: ITS ROLE IN COMPLEX TRAITS AND SPECIATION Principal Investigator & Institution: Wade, Michael J.; Professor; Biology; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007
22
Male Infertility
Summary: (provided by applicant): Our goal is to better understand the role of gene interactions (epistasis) in producing complex phenotypes using a combination of theoretical models, quantitative genetics, molecular genetics, and experimental populations of flour beetles, genus Tribolium. Our specific goals are to isolate, map, and compare the genes that interact to cause a reduction of mating success, viability, and fertility in (1) inter-population crosses, with those causing fitness reduction in (2) interspecific crosses. Incompatibility genes interact in the same way as those genes causing human genetic diseases, cancer susceptibility, and pathogen resistance. First, we will investigate the genetic basis of (1) pre-zygotic male infertility; and, (2) post-zygotic reproductive isolation observed in inter-population crosses of T. castaneum. Our statistical genetic studies indicate that maternal effects and epistasis cause reduced viability and fertility fitness in F2 and backcrosses between 3 pairs of populations from collected from Central America, South America, and Africa. However, because statistical genetic methods average positive and negative effects of different gene combinations, we will use a microsatellite map of the Tribolium genome to dissect the average effects of gene interactions into their single locus components. Because each of 3 pairs of partially isolated populations is fully inter-fertile with a laboratory strain, we will create recombinant congenic lines by reciprocal backcrosses to the lab strain in order to isolate those genes in each of the two backgrounds, which, when combined-by inter-population crosses, cause reproductive incompatibility. Second. we will identify the genes in T. castaneum, which interact with one another and with genes from T. freemani, to cause hybrid male deformities and hybrid male inviability in inter-specific crosses. We will compare the sets of genes reducing fitness in inter-population crosses in T. castaneum with those diminishing the fitness of its inter-specific hybrids with T. freemani. We can determine whether the genes interacting to reduce the fitness of T. castaneum interpopulation crosses are a subset of those reducing hybrid fitness in inter-specific crosses. The latter must include some gene differences accumulated after speciation. Alternatively, the barrier to gene exchange between T. castaneum and T. freemani may represent either, a sample of the genes posing incipient barriers, to gene exchange between populations of T. castaneum, or it may be unique. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FLAGELLAR MOTILITY AND ASSEMBLY Principal Investigator & Institution: Witman, George B.; Professor; Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 01-AUG-1981; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term goals are to understand the assembly and function of cilia and flagella. Most of the research is being carded out using Chlamydomonas, because its flagella are readily studied by a combination of genetic, molecular genetic, biochemical, and cell biological approaches. Additional studies are being carded out in the mouse. Biochemical studies will test the hypothesis that the recently identified ODA5 protein is part of a previously unknown complex that is necessary for assembly of the outer dynein arm onto the Chlamydomonas flagellar axoneme. If so, cDNAs encoding the other components of the complex will be isolated and sequenced, and mutants with defects in these genes will be identified and characterized. Intraflagellar transport (IFT), which moves particles from the cell body to the tip of the flagellum and then back to the cell body, is important for the assembly of all cilia and flagella. Chlamydomonas cytoplasmic dynein lb, the retrograde IFT motor, will be analyzed to determine its subunit composition, and cDNAs encoding newly identified subunits will be cloned. Pulse-label studies will determine if any subunits are
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phosphorylated, which would suggest a role in the control of dynein lb. lmmunofluorescence microscopy of mutants expressing modified forms of dynein lb's light intermediate chain, D lbLIC, will be carded out to elucidate the roles of D lbLIC' s P-loop and phosphorylation sites. Chlamydomonas insertional mutants with reduced levels of dynein lb will be characterized to identify the defective genes, which may encode previously unidentified subunits of dynein lb. Mutants with defects in the IFFparticle proteins IFF20, IFF46, and IFF57 will be studied to understand the functions of these proteins. IFF particles from the mouse testis will be isolated and characterized to determine their composition, structure, and cargo. The epithelial cells lining the follicles of the thyroid gland have well-developed primary cilia, but the function of these cilia is unknown. Thyroids of Tg737 xk mice, which are defective in IFT, will be examined by scanning electron microscopy to determine if they fail to assemble normal primary cilia, and sera of mutant mice will be assayed to determine if thyroid hormone levels are abnormal. If so, the mutant thyroids will be studied by histology and electron microscopy to understand how the lack of primary cilia affects thyroid function. The studies promise to increase our understanding of a wide range of human diseases, including primary ciliary dyskinesia, in which the dynein arms are frequently missing, male infertility, and thyroid disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FSH - RESPONSIVE GENES IN MOUSE SERTOLI CELLS Principal Investigator & Institution: Kumar, T Rajendra.; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 08-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): In the male, follicle stimulating hormone (FSH) binds to G-protein coupled transmembrane receptors on the Sertoli cells and controls their development and function. Sertoli cells are the somatic cells of the testis that provide physical scaffolding and various signaling factors to the proliferating and differentiating germ cells. During the mouse testis development, Sertoli cells rapidly divide up to postnatal day 14, thereafter cease to proliferate and terminally differentiate. The number of Sertoli cells determines the germ cell capacity and thus the male reproductive potential. Aberrations in Sertoli cell proliferation and differentiation may cause male infertility. Despite this knowledge, the molecular basis for FSH regulation of Sertoli cell proliferation and differentiation is unknown. A major challenge to study the mechanism of FSH action in the male has been to rapidly isolate pure Sertoli cells (free of contaminating testis cell types) that accurately reflect their in vivo function. The longterm goal of this project is to understand how FSH regulates distinct developmental programs in Sertoli cells by orchestrating various gene/protein networks. In Specific Aim 1, we will isolate pure populations of Sertoli cells by two approaches. In the first approach, a rapid magnetic cell separation method will be used to selectively enrich Sertoli cells based on their unique cell surface expression of FSH-receptors. In the second approach, Sertoli cells will be enriched from two different strains of transgenic mice expressing an enhanced green fluorescent protein (EGFP) marker (driven by either Mullerian inhibiting substance or Pem homoebox promoter) specifically in the Sertoli cell lineage. Additionally, by crossbreeding, the GFP transgenes will be introduced into the FSH-null background. Pure populations of Sertoli cells will be isolated from both these strains of mice (with and without FSH) by flow cytometry. In Specific Aim 2, to begin to identify FSH-responsive genes, we will use subtractive hybridization strategies to enrich Sertoli cell-specific cDNAs or use cDNA microarrays to analyze large-scale gene expression changes in pure populations of Sertoli cells (isolated in Specific Aim 1)
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Male Infertility
during proliferation (day 10) and differentiation (day 42) phases. Collectively, these experiments will enable us to monitor the development of GFP-expressing Sertoli cells in vivo, develop rapid methods to purify Sertoli cells and identify and characterize the FSH-responsive genes in them. Finally, the GFP transgenic mice and the Sertoli cell specific cDNAs and large-scale gene expression profiles generated in this pilot grant will be valuable reagents and will be made available to a number of investigators engaged in male reproductive endocrinology and developmental biology research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION FERTILIZATION
OF
GAPDS
DURING
SPERMATOGENESIS
&
Principal Investigator & Institution: O'brien, Deborah A.; Associate Professor; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Description (provided by applicant): Glycolysis is required for mammalian sperm function and fertilization. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS), a unique isozyme expressed only during the late stages of spermatogenesis, appears to serve a pivotal role in regulating this metabolic pathway in spermatozoa. GAPDS has a novel N-terminus that tightly anchors it to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. GAPDS is more susceptible than somatic GAPD to inhibition by substrate analogs, which induce rapid and reversible male infertility. The long-term goal of this study is to identify mechanisms that regulate sperm glycolysis anc fertilization. The specific aims are to: 1) Determine if localization of GAPDS to the fibrous sheath is required for normal sperm function. These experiments will use knockout and transgenic mice to identify sequences required for GAPDS targeting and binding to this cytoskeletal structure, and to test the hypothesis that anchoring of GAPDS to the fibrous sheath is critical for normal sperm glycolysis, hyperactivated motility, and fertilization; 2) Identify protein interactions that anchor GAPDS to the fibrous sheath. The fibrous sheath, which serves as a scaffold for both glycolytic enzymes and protein kinase A subunits, is likely to be an important regulator of sperm motility. Proteins that interact with GAPDS will be identified by coimmunoprecipitation and yeast two-hybrid assays to better understand the formation and function of protein complexes along the fibrous sheath; 3) Determine if GAPDS plays a role in the assembly of sperm glycolytic enzymes or the phosphorylation cascade that occurs with hyperactivation. Because GAPDS is tightly bound to the fibrous sheath, it is well positioned to participate in the localization of other glycolytic enzymes to the principal piece of the sperm tail and in the regulation of hyperactivated motility. These studies will determine if GAPDS is required for the localization of other glycolytic enzymes to the principal piece, and if initiation of hyperactivated motility alters the activity, solubility, or phosphorylation status of GAPDS; 4) Identify key amino acids that are responsible for the novel enzymatic properties of GAPDS. Molecular modeling studies have identified eight amino acids near the substrate and cofactor binding sites of GAPDS that are different from somatic GAPD. Site-directed mutagenesis will be used to determine the effects of these amino acids on GAPDS activity and inhibition. These studies will determine if the human ortholog of GAPDS is a feasible target for developing highly specific male contraceptives, and if suppression of GAPDS activity by environmental and therapeutic agents could be a cause of infertility in men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL ANALYSIS AND REGULATION OF EPIDIDYMAL OCTN2 Principal Investigator & Institution: Hinton, Barry T.; Professor; Cell Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Protection of cells from osmotic stress is critical for their survival as cells will undergo apoptosis if not protected. Epididymal luminal fluid is hypertonic and therefore epididymal cells need to adapt to the higher osmolality to limit the effects of osmotic stress. Like the kidney, the epididymis accumulates osmolytes to adapt to changes in osmolality. Movement of osmolytes is achieved by specific transporters, e.g. sodium-myo inositol cotransporter which transports the osmolyte myo-inositol. L-carnitine is another osmolyte that plays a key role in the adaption of hyperosmolality and is found in high concentrations in epididymal luminal fluid. Therefore, this study will examine how the transporter for L-carnitine, Novel Organic Cation Transporter 2 (OCTN2), plays a critical role in allowing epididymal cells to adapt to a hyperosmotic environment and ultimately protecting themselves from osmotic stress. Our working hypothesis is that osmotic stress of epididymal cells results in an influx of ions which increases the intracellular ionic strength. This increase activates the MAPK pathway, which in turn induces transcription of hypertonicity responsive transcription factors, e.g. TonEBP. These transcription factors then bind to their cognate binding sites on the OCTN2 promoter and allow transcription of OCTN2 to proceed. The transport protein is then translated, trafficked to the basolateral membrane and L-carnitine transported into the cell. Accumulation of the osmolyte, Lcarnitine, will counteract the effects of ions by stabilizing key proteins and DNA. At this stage the epididymal cells have adapted to the new osmotic enviroment and afforded themselves protection from osmotic stress. Specifically, the following hypotheses will be tested: (1) OCTN2 is responsible for transport of L-carnitine into the epididymis; (2) The OCTN2 promoter is regulated by tonicity responsive transcription factors; (3) OCTN2 transcription and transporting activity are regulated by changes in tonicity via specific signal transduction pathways; (4) Loss of OCTN2 results in the loss of the ability of the epididymal epithelium to adapt to a hyperosmotic enviroment resulting in susceptibility to osmotic stress leading to epididymal dysfunction and male infertility. The findings from this proposal will provide fundamental information for the treatment of certain forms of male infertility and for the development of a male contraceptive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL ANALYSIS OF THE T COMPLEX Principal Investigator & Institution: Schimenti, John C.; Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002; Project Start 01-MAY-1988; Project End 30-JUN-2007 Summary: (provided by applicant): The DNA sequence of the human genome provides the foundation for elucidating the functions of genes on a large scale, and understanding the consequences of genetic perturbations on human health. We propose to continue studies using the mouse as a model for uncovering gene functions in mammals, concentrating on a particularly fascinating region of the genome known as the t complex on chromosome 17. Variant alleles or mutations of genes within the t complex cause a variety of phenotypes, including embryonic lethality, male infertility, segregation distortion, hybrid sterility, parent-of-origin (imprinting) effects, and sex reversal. Most of these phenotypes are associated with naturally-occurring, variant forms of the t
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Male Infertility
complex known as t haplotypes. Classical genetic analyses of these mutations are largely ineffective, due to inversions in the t haplotypes that prevent recombination. Other phenotypes are only revealed in the context of segmental aneuploidy, and thus the underlying genes are also refractory to meiotic mapping. To identify genes underlying these t complex phenomena and to identify new functions along this region of the genome, we have developed a series of overlapping chromosomal deletion complexes that overlap in an interdigitated fashion. In the proposed work, this collection of deletions and other molecular genetic approaches will be used to: 1) Characterize and clone newly discovered haplolethal and imprinted loci; 2) Identify the T associated sex reversal locus (Tas); 3) Identify the gene or genes underlying the tw18 mutation, which disrupts gastrulation due to defective mesoderm migration and survival; and 4) Identify new genetic functions in the t complex by systematically generating mice that are nullizygous for various t complex intervals, using combinations of deletions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL GENOMIC APPROACH TO MALE CONTRACEPTION Principal Investigator & Institution: Xu, Eugene Y.; Center for Reproductive Sciences; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Modern contraceptive methods have a surprisingly short history and are dominated by a few methods such as the oral contraceptive pill for women or physical barrier methods such as condoms for men. In spite of the lack of choice of methods, studies show that men aspire to play a greater role in the regulation of fertility. Some effort in the past has been focused on development of male contraceptives, which focused on hormonal and immunological control of spermatogenesis, but few studies have focused on developing a male contraceptive that will alter the activity of key genes that regulate spermatogenesis. This is the approach that we outline. It is a timely approach, as with the completion of the human genome project and those of model organisms, we have unprecedented knowledge of the genes and proteins that are likely to govern the development of sperm. In our preliminary studies, we have identified genes that encode male fertility factors in Drosophila, discovered homologs in mice and humans, and begun to explore mechanisms of male infertility by examining the phenotypes of sterile mutant flies and knockout (KO) mice. The objectives of this research are to identify and to characterize novel gene targets involved in the regulation of male fertility and to lay the ground work for the development of male contraceptives against those targets. We will screen a mouse ES gene trap cell library for male reproductive genes identified through our comparative genomics analysis, to generate mouse KO mutants disrupting the conserved male fertility factors, to characterize the roles of those key regulators during sperm production and maturation, and finally to provide a resource of male reproductive mutants for researchers in the contraceptive field, as well as in the reproductive field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDIDYMIS
FUNCTIONAL
SIGNIFICANCE
OF
HOX
GENES
IN
THE
Principal Investigator & Institution: Bomgardner, Daniela; Urology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007
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Summary: Dr. Daniela Bomgardner is committed to an academic career. , focusing on basic research in reproductive medicine with the goal of being an independent investigator. Her current training has broadened her knowledge in cellular and molecular physiology of the reproductive tract. The KO8 will provide a unique opportunity for her to learn more advanced methods in molecular and cellular biology and to become more proficient and experienced in experimental planning and critical data analysis. The Department of Urology is dedicated to the candidate's research development and is committed to ensure protected time for research. The combination of the sponsors productive laboratory, the molecular and cellular core facilities at UVA, and the collaboration with Dr.'s H. Scrable and S. Zeitlin (Dept. Neuro-science, UVA) provides and excellent environment for learning new research techniques and approaches to scientific problems. Importantly, the candidates advisory committee, composed of established investigator with pertinent but diverse areas of expertise, and is strongly supportive of this project. Moreover, the expertise of Dr. B. Hinton (Dept. of Cell Biology, UVA) and Dr. M. Wilkinson (Dept. of Immunology, M.D. Anderson Cancer Center, Houston, TX) will provide additional support for the candidate's goal of becoming an independent investigator. The long-term objective of this proposal is to discover the mechanism underlying the development and maintenance of segmental function in the epididymis. Sperm maturation in the epididymis requires epithelial gene products expressed in a region-specific pattern. Our hypothesis is that hox genes are master regulators of this process. These genes are known to be crucial in segmental patterning of the embryo, but adult function of these genes is unknown. Specifically, it is proposed to develop a conditional mutation of the endogenous hoxa-11 gene. It is hypothesized that the down-regulation pathway of hoxa-11 includes Meis 1 as a DNAbinding cofactor and L1-CAM as a potential target. The gene and protein expression pattern of each participant in this pathway will be analyzed. The resulting data will be used as a baseline to test the hypothesis that temporal regulation of hoxa-11 influences critical periods in development and adult epididymal function. Finally, the hypothesis, that specific 5' hox genes can transactivated particular downstream targets together with DNA-binding factors will be investigated. A broad spectrum of modern research techniques will be used including state-of- the-art in vivo experiments. Findings from this proposal will provide fundamental information for the understanding of basic biological processes important in certain forms of male infertility and in certain urological dysplasias in pediatric urology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL STUDIES OF THE CDY GENE FAMILY Principal Investigator & Institution: Lahn, Bruce T.; Human Genetics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The long-term goal of this proposal is to determine the function of a newly discovered gene family known as the CDY family in mammalian spermatogenesis. Founding members of this family are the human Y chromosomal genes CDY1 and CDY2 (together referred to as CDY). The CDY genes are linked to spermatogenic failure, as CDY1 maps to a region of the Y chromosome frequently deleted in infertile men. The role of CDY in spermatogenesis is further supported by its testis-specific expression. Other members of the CDY family are autosomal, and have expression patterns consistent with roles in both spermatogenesis and somatic development. This family of genes is shown by biochemical studies to encode a novel class of histone acetyltransferase enzymes, and are thus implicated in chromatin
28
Male Infertility
modification. The primary objective of this proposal is to test the hypothesis that the spermatogenic function of the CDY family is to promote chromatin condensation during spennarid maturation. Our specific aims are: 1) To determine the precise expression profile and protein localization of this gene family during spermatogenesis. 2) To biochemically characterize the CDY family, focusing on identifying factors that engage in protein-protein interactions with members of the family, and on characterizing the enzymatic properties of these histone acetyltransferase enzymes. 3) To construct knockout and transgenic mice involving members of the CDY family, and to use these mouse models for assessing the in vivo functions of these genes. Collectively, these developmental, biochemical and genetic studies should shed light on the organismal function of the CDY family. Specifically, they will aid in evaluating the hypothetical role of this gene family in promoting chromatin condensation during spermatid maturation. Results will also have implications for understanding the molecular etiology of male infertility, and for developing drug-based male contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GCD MOUSE--MODEL FOR HUMAN AZOOSPERMIA Principal Investigator & Institution: Bishop, Colin E.; Professor; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002 Summary: Germ cell development is a complex, strictly ordered process of cell division and differentiation starting with the segregation of diploid primordial germ cells (PGCs) from the somatic lineage and finishing with the production of large numbers of mature haploid spermatozoa or oocytes. It is an essential determinant of fertility in all mammals, playing a fundamental role in the perpetuation of the species, maintaining its genetic diversity and driving evolution. Recently, considerable progress has been made in identifying genes that play a role in the later meiotic stages of germ cell progression. However, very little is known about the pathways involved in the very earliest stages of PGC development. development. In fact, only four genes in the mouse have known, specific effects on PGCs (MGF, Kit, Ter, gcd). Mutations in each cause PGC deficiency and fertility problems. With the exception of gcd, these mutations are pleiotropic making an analysis of the specific germ cell component more difficult. The present proposal is designed to fill this gap in our knowledge, by identifying specific genes involved in the migration and proliferation of PGCs. The non-pleiotropic germ cell deficient (gcd) mouse mutant will be used as a model system. Analysis of this mutant clearly shows that disruption at a single locus, can drastically reduce the PGCs in the embryonic gonad, giving rise to male and female infertility. The male phenotype of a severe oligospermia quickly followed by azoospermia with only a few functional tubules, is very similar to the human Sertoli Cell Only syndrome (SCOS) seen in infertile human males. The specific aims of this project are designed to identify the gene underlying the gcd phenotyping using positional cloning and gene targeting. Its structure, spatio-temporal expression pattern and possible of studied by reintroducing the gene into gcd/gcd mice via transgenesis. That the cloning of gcd represents a unique opportunity to gain new insights into the fundamental biology of primordial germ lines and the intractable problem of infertility in humans. It will allow us to examine the possibility that errors in the GCD gene itself, or in a pathway which in controls, underlie a significant percentage of such cases in human. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC STUDIES OF SPERMATOGENIC FAILURE IN HUMANS Principal Investigator & Institution: Page, David C.; Professor/Investigator; Whitehead Institute for Biomedical Res Biomedical Research Cambridge, Ma 02142 Timing: Fiscal Year 2002; Project Start 10-MAY-2000; Project End 30-APR-2005 Summary: (Adapted from investigator's abstract): The broad, long-term objective of this application is to explore the role of genetic defects in human male infertility. Millions of men who are otherwise healthy produce few or no sperm, resulting in infertility. In the great majority of such otherwise normal men, the causes of spermatogenic failure cannot be pinpointed at present. Numerous studies have addressed the possible roles of infectious agents, immune processes, varicoceles, chemical insults, or other physiologic or environmental factors. By contrast, the present application focuses on genetic factors. More specifically, this application will test the hypothesis that unidentified mutations in specific X-linked genes and Y-linked genes are significant causes of unexplained spermatogenic failure in otherwise healthy men. One thousand men with spermatogenic failure will be tested for deletions or point mutations in 30 candidate genes located on the X or Y-chromosomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOME ARCHITECTURE IN HUMAN SPERM CELLS Principal Investigator & Institution: Zalensky, Andrei O.; Associate Professor; Biological Chemistry; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 08-AUG-2002; Project End 31-MAY-2005 Summary: The mammalian spermatozoa is a unique cell type in which the DNA is arranged into a compact and genetically inert state. Recently, the existence of a welldefined spatial organization of genome - genome architecture (GA) have been shown in spermatozoa of humans: each chromosome occupies distinct territory, all centromeres are clustered into a compact chromocenter buried within the nucleus, while all telomeres are exposed at the periphery and interact to form dimers. The general hypothesis is that non-random sperm GA determines and promotes an ordered chromosome withdrawal and movements during successful fertilization. In particular, defective GA in some cases of (male infertility may have an adverse impact on early development. The long-term goal is to establish the "standard" of how chromosomes are packed and arranged in normal, fertile human sperm, and to develop in situ tests for proper selection of donor cells during assisted reproduction. The first objective is to unravel as yet unknown characteristics of GA in sperm of donors with proven fertility. In preliminary experiments a new approach to directly observe chromosome organization in sperm has been developed. In the proposed study, nuclear path and higher- order structures of individual chromosomes will be established. Next, the nature of telomere dimers will be analyzed. Preliminary data indicate that these are formed by interactions between two ends of one chromosome. If so, chromosomes in human sperm nuclei are looped. Further, nuclear positioning of individual chromosomes will be determined. Strong indications towards non-random spatial arrangement of chromosomes in sperm nuclei have been obtained in preliminary studies. The second objective is a systematic study of GA in spermatozoa of men with abnormal sperm morphology undergoing treatment with IVF/ICSI. These studies will establish how chromosomes are packed and arranged in fertile human sperm and will lead to a better understanding of the role played by the male genome spatial organization at fertilization. The information obtained should contribute to an improvement of
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Male Infertility
diagnostic assays and better prediction of the outcome of assisted reproduction. Finally it will add to our basic knowledge about structural organization of chromosomes in human cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLYCOSPHINGOLIPIDS CONTRACEPTION
AS
TARGETS
FOR
MALE
Principal Investigator & Institution: Platt, Frances M.; University of Oxford University Office, Wellington Sq Oxford, Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): The development of male contraceptives is highly desirable, as worldwide there is a large unmet need for alternative methods for family planning. Therefore, it is important to identify and investigate ways, by which male fertility can be regulated. Oral administration of the alkylated imino sugars Nbutyldeoxynojirimycin (NB-DNJ) and N-butyldeoxygalactonojirimycin (NB-DGJ) causes reversible infertility in male mice. The mice are infertile because they produce morphologically abnormal spermatozoa that are mostly without acrosomes, and have reduced motility. To understand the chain of events underlying this phenomenon, the long-term objectives are the following: (1) Identify the biochemical processes that are modulated, directly, or indirectly, by alkylated imino sugars that cause male mice to be infertile; (2) Correlate these biochemical changes with the cell biological peculiarities seen in testes from mice after administration of alkylated imino sugars. The proposed research has three components. (1) Significance of known drug targets. Investigated will be whether male infertility is caused by inhibition of one of the known targets of NBDNJ and NB-DGJ, which are the ceramide-speciflc glucosyltransferase and a nonlysosomal glucosylceramidase. These enzymes are involved in the metabolism of a glycosphingolipid, glucosylceramide. Assessed will be the effects of NB-DNJ on the level of testicular glucosylceramide, as well as its cellular and subcellular distribution, and the localization of the enzyme that is the primary drug target. (2) Novel drug targets. Since the alkylated imino sugars are ceramide-mimics, it is essential to establish whether these compounds also affect the metabolism of glycolipids other than glucosylceramide. This may lead to the identification of additional drug targets. (3) Consequences of altered glycosphingolipid metabolism for male germ cell development. The following aspects of the biochemistry and cell biology of spermatids will be studied: crosstalk between sphingolipid and phospholipid metabolism, the lipid and protein composition of sphingolipid/cholesterol-enriched microdomains, trafficking and turnover of acrosomal proteins, and ultrastructure. To develop reagents for the investigation of acrosome development, a proteomic analysis of this organelle will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GONADAL AND ENDOMETRIAL FUNCTION IN HUMAN REPRODUCTION Principal Investigator & Institution: Giudice, Linda C.; Professor; Gynecology and Obstetrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 07-APR-1997; Project End 31-MAR-2007 Summary: Our currently funded NIH U-54 SCCPRR Center has provided the foundation for a rich, interactive environment for the pursuit of and training in reproductive biology and medicine at Stanford University. It consists of an integrated
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group of investigators in the Department of Gynecology and Obstetrics and for this competitive renewal adds an investigator in Developmental Biology and In Situ Hybridization Core, and Bioinformatics Core). The projects are designed to investigate molecular mechanisms governing reproductive processes in the ovary, endometrium, and testis, and to benefit specifically from interactions among investigators and cores. The central endometrium, and testing, and to benefit specifically from interactions among investigators and cores. The central theme of the Center is gonadal and endometrial function in reproduction, with a focus on the human, thereby enhancing the long-term goal of translational research to clinical reproductive disorders, including infertility and poor pregnancy outcome. Projects by Hsuehi and Conti interact, as they focus on early ovarian follicle development and on the role of mechanisms governing meiosis in the female gonad, respectively. Project by Giudice investigates auto/paracrine mechanisms in human implantation, primarily involving the IGF system. It interacts extensive with Project by Conti from the perspective of signaling mechanisms and Project by Fuller due to new findings in human endometrium of the Drosophila homologs important in cell-cell interactions. In this renewal, we will welcome a new project (Fuller) that focuses on early events in meiosis in the male gonad, using the Drosophila model. It interacts with Project by Hsuehi, Conti and Giudice. The pilot project (Tazuke) focuses on early germ cell development in the male gonad using the Drosophila model with a translation to the human. It interacts will allow projects. The enter is highly enriched by the University environment with seminars, courses, conferences, and core facilities. Issues of female infertility and fertility are critical to the national agenda to improve women's health care. Male factors also contribute significantly to reproductive failure, and understanding their pathogenesis and treatment is very important. Our Center's goal is to investigate basic cellular and physiologic processes involve din normal reproductive function, laying the foundation to understand abnormal follicle failure, male infertility, miscarriage and ectopic pregnancy. Advances in the enter are anticipated to lead to new diagnostic and therapeutic modalities for reproductive disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GROWTH SPERMATOGENESIS
FACTOR
SIGNAL
TRANSDUCTION
AND
Principal Investigator & Institution: Morris, Patricia L.; Senior Scientist; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2002; Project Start 26-APR-2001; Project End 28-FEB-2006 Summary: (Adapted from the applicant's abstract) As growth factors, cytokines are known mediators of both normal proliferation and aberrant cell cycle-related responses in the hematopoietic and immune systems. Deficiencies as well as inappropriate expression of specific cytokines in vivo is associated with disruptions in spermatogenesis. These findings are suggestive of their role in pro- and antiproliferative effects within the male germ cell lineage. The biological activities of multiple cytokines and growth factors are mediated through cognate receptors and specific receptor-associated kinases (JAK). Distinct protein-protein interactions are critical for these signal transduction events leading to an induction of gene expression through a family of latent transcription factors called STAT proteins. Recent studies have identified several members of the JAK tyrosine kinases and cytokine/growth factor receptors in specific male germ cells. The working hypothesis is that an imbalance between the levels of critical growth factors can result from a hostile environment. It is proposed that such extra cellular stimuli can generate inappropriate signals within
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Male Infertility
receptor-positive developing germ cells at the level of two of their kinase pathways (JAK and MAPK). Three specific aims are proposed to test the PI's working hypothesis. (1) To characterize the effects of these growth factors on germ cell DNA synthesis and cell cycle progression and, to determine the interactions of the retinoic acid receptors and cytokine signaling on cell proliferation. (2) To establish the role of the SOCS family of cytokine-inducible inhibitors and, determine the role of intracellular compartmentalization in STAT function. (3) To characterize the cross-talk between IL6 and MAPK signaling in germ cell proliferation and, to test whether germ cells exposed to inflammation or environmental toxicants can be rescued from apoptosis by growth factor/cytokine rescue. It is the PI's long term goals to include the identification of novel sites for therapeutic intervention to prevent disruption of germ cell development during infection, inflammation and in cytokine-based male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCO3 AND NA+ TRANSPORT IN HUMAN & PIG VAS DEFERENS Principal Investigator & Institution: Schultz, Bruce D.; Assistant Professor; Anatomy and Physiology; Kansas State University 2 Fairchild Hall Manhattan, Ks 665061103 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The long-term goal for this project is to determine the epithelial ion transport pathways and the associated regulatory mechanisms within the distal male genital tract in order to provide a basis for better understanding reproductive dysfunction. Ion transport processes within the distal ductus deferens (dDD) have not been clearly identified although errant ion transport within the duct is clearly associated with asthenozoospermia, oligozoospermia, non-obstructive azoospermia, and obstructive azoospermia. Recent observations point to a novel constellation of Na+-dependent ion transport pathways within the dDD. The cellular and molecular basis of these observations remains to be determined. We hypothesize that specific cells in dDD epithelium are capable of regulated Na+-dependent HCO3secretion and/or Na + absorption. These processes may occur independently in separate cell populations or may be simultaneously expressed in a single cell population. The epithelial model that is proposed represents a paradigm shift from currently held views regarding dDD function. This new epithelial model provides for neurotransmitterdependent mechanisms to acutely alkalinize the lumen for sperm activation just prior to ejaculation and provides a basis to account for male factor infertility that is currently diagnosed as 'idiopathic.' Modem electrophysiological, biochemical, cytochemical, and molecular techniques will be employed to study native epithelium along with primary cell cultures to delineate the mechanisms and signaling pathways that contribute to epithelial function with the ultimate goal of modulating male fertility. The hypotheses will be tested by addressing the following specific aims. Aim 1. To identify key mechanisms that contribute to HC03 transport across distal ductus deferens pithelia. Aim 2. To identify key mechanisms that contribute to Na vtransport across distal ductus deferens epithelia. Results from these studies will lead to an increased understanding of male reproductive tract function along with a more complete understanding of Nav and HCO3 transport mechanisms in general. The proposed studies will ultimately benefit the medical community by providing rational bases for therapeutic interventions both to treat male infertility and to modulate male fertility (i.e., male contraception). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONE CONTROL OF SPERMATOGONIAL ARREST IN MUTANT MICE Principal Investigator & Institution: Meistrich, Marvin L.; Professor; Expermtl Radiation Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Juvenile spermatogonial depletion (jsd) mice initiate a wave of spermatogenesis at puberty, but then sperm differentiation ceases despite the continued presence of A spermatogonia. Although the mechanism is not known, we showed that testosterone (T) inhibits spermatogonial differentiation, which can be restored with GnRH antagonist or estradiol (E2). We hypothesize that inhibition of spermatogonial differentiation in jsd mice is due to the action of T on gene expression in a specific somatic cell (Sertoli, Leydig, peritubular myoid, or arteriolar smooth muscle). We utilize the power of mouse genetics to elucidate the mechanism by which T mediates spermatogonial "arrest" in jsd mice and begin identifying the cell type and hormonally regulated gene(s) involved in the following Aims: (I) To establish the specific role of androgen and not FSH, we will complete studies using jsd mice also carrying mutations in the androgen receptor (AR) and FSHbeta genes. To determine the mode and the site of action of E2, the restoration of spermatogenesis with GnRH-antagonist and E2 treatment will be compared in jsd mice with that in jsd mice carrying mutations for estrogen receptor (ER)-alpha or for ERbeta. (II) To establish that the hormones affect spermatogonial differentiation by direct action on the testis and/or seminiferous tubules, we will examine their effects on spermatogonia in in vitro cultures of testicular tissue and tubules from jsd mice. (III) To identify the cell that is the target for hormonal inhibition of spermatogonial differentiation, we will transplant tubules between jsd mice and AR-deficient jsd mice and use cell-type specific elimination of an AR gene with loxP sites using Cre-recombinase driven by promoters specific for the different somatic cells. (IV) To identify the responsible gene, we will differentially screen for candidate hormone-regulated genes in the target cell of jsd mice using microarrays. A good candidate gene must have its level changed by GnRH antagonist in one direction and by T in the opposite direction. Elucidation of the mechanism of this spermatogonial "arrest" and its reversal in the jsd mouse could apply to cases of genetically determined male infertility. Because of its remarkable similarity to the failure of spermatogonial differentiation in toxicant-treated and aging rats, these results could also apply to azoospermia induced by reproductive toxicants and the decline in spermatogenesis with aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN SPERM ZONA ACCEPTOR: ENVIRONMENTAL EFFECTS Principal Investigator & Institution: Benoff, Susan H.; Associate Professor; North Shore University Hospital 300 Community Dr Manhasset, Ny 11030 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 31-JUL-2006 Summary: (provided by applicant): We focus on developing an understanding of toxic metal action in the human testis. A male factor is present about 60% of infertile couples, but underlying molecular mechanisms are largely uncharacterized. Exciting results from our current work hints at one mechanism. Lead levels were elevated markedly in testes and seminal plasma (in 25% of males in four independent populations). High lead correlated with expression of particular potassium and calcium ion channel isofomis, with poor sperm-fertilization-potential biomarkers and low fertility by IVF, artificial insemination and coitus. A significant fraction of subjects studied longitudinally
34
Male Infertility
switched from high lead states to low lead states, with simultaneous conversion of biomarkers from infertile to fertile and switch in potassium channel isoform expression. This suggested lead epigerietically modified testicular gene expression (at the levels of transcription and mRNA splicing) and that potassium channel isoforms could be developed as biomarkers for lead exposure. A preliminary DNA microarray study of a lead-treated "lead-resistant" rat strain identified many lead-affected genes as being involved in calcium-mediated induction of apoptosis, including a potassium channel. Supported by current somatic cell apoptosis mechanisms, this prompted our hypothesis that lead exposures produce male infertility by altering calcium homeostatsis, and a related detailed mechanism of lead action. These will be tested in a lead-treated leadsensitive" rat strain and in humans. We will use microarrays to probe in rats for affected testicular genes with CAMP response elements and other genes involved in calcium/calmodulin-dependent protein kinase IV signaling. Controls include metal testing by atomic absorption, TUNEL estimates of apoptosis, cell type levels by histology and by cell-type-specific mRNA levels, and protein expression by Westerns. Comparison with the "lead-resistant" strain should identify lead-sensitivity" genes. We will probe for the same genes in a human clinical population, with similar controls. We will also probe for genes co-regulated with the potassium channel above. Results will test several specific steps in our proposed mechanism: verifying, negating or modifying it. Because microarrays cannot detect differential calcium channel splicing events correlated with lead effects upon human testes, this gene and other calcium transporters will be studied by immunocytochemistry, RT in situ PCR and real-time PCR. Outcome is test of hypothesis, and possible mechanism explaining infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis, and hope for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRATESTICULAR TESTOSTERONE AND SPERMATOGENESIS Principal Investigator & Institution: Jarow, Jonathan P.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: It is well established in animals and humans that the maintenance of normal spermatogenesis is critically dependent upon the presence of androgenic steroids within the testis. Studies in the rodent have shown that intratesticular testosterone concentrations are normally thirty-fold higher than serum concentrations, and that levels of intratesticular testosterone ten-fold greater than serum are required to maintain spermatogenesis. It is incredible that the concentration of testosterone in the normal human testis is not known. The long-term objectives of this project are to study the relationship between intratesticular testosterone concentration and spermatogenesis in humans, and to understand the role that inadequate intratesticular testosterone concentration might play in male infertility. The intratesticular concentration of testosterone, its precursors and metabolites, in normal fertile men will be determined by examining testicular fluid obtained by direct percutaneous aspiration from fertile men undergoing vasectomy. Biologically available intratesticular testosterone will be estimated by simultaneously measuring the intratesticular androgen binding proteins, steroid hormone binding globulin (SHBG) and androgen binding protein (ABP). The range of the minimally necessary intratesticular concentration of testosterone required for the maintenance of quantitatively normal spermatogenesis will be estimated by measuring the intratesticular testosterone concentration of men receiving contraceptive doses of testosterone and men with partial hypogonadism prior to their receiving testosterone replacement therapy. The range of intratesticular testosterone concentration
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in infertile men diagnosed with idiopathic infertility and with varicoceles will be determined. Additionally, the pathophysiological mechanism for abnormally low intratesticular testosterone concentration will be studied in subfertile men. We will directly test the hypothesis that reduced intratesticular testosterone concentration is responsible for infertility by examining the correlation between intratesticular testosterone concentration and improvement in spermatogenesis in infertile men receiving therapies designed to increase intratesticular testosterone concentration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MALE SPERMATOGENESIS
FERTILITY
&
PROTEIN
EXPRESSION
IN
Principal Investigator & Institution: Haynes, Susan R.; Assistant Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: A thorough understanding of spermatogenesis is important for advances in male infertility research and male contraceptive development. The long-term goal of this research is to understand how posttranscriptional regulatory mechanisms control the expression of sperm proteins. The translational repression of some mRNAs at specific periods during spermatogenesis is a key strategy that is used in plants, insects and mammals. Recent genetic and molecular studies of spermatogenesis in the fruit fly Drosophila have identified three components of a translational repression pathway. These are the RNA binding protein TSR, the Scpr mRNA that it regulates, and the GTPbinding protein ARF, which binds TSR and may modulate its function. With this information, it is now possible to address fundamental questions about the mechanism of translational regulation, using a combination of genetic, molecular and biochemical approaches. The first specific aim of this proposal focuses on a detailed characterization of the TSR-Scpr mRNA interaction, and how Scpr mRNA becomes activated for translation at the appropriate time. In vitro binding studies will be used to identify the sequences required for the interaction, and their biological relevance will be tested in transgenic flies. The second aim is to generate mutations in ARF and study its function in vivo during spermatogenesis. The effects of these mutations on Scpr and TSR will also be assayed. The final specific aim will address the question of how the TSR-ARF protein-protein interaction is regulated, and the effect of that interaction on the subcellular localization of TSR. The yeast two-hybrid system will be used with wild type and mutant proteins to define the role of guanine nucleotides in the interaction and the regions of TSR that are important for protein binding. Additional experiments will use immunoelectron microscopy to examine the localization of TSR and ARF in developing spermatocytes and spermatids. Given the fact that human testis proteins related to Scpr have important roles in spermatogenesis, the results of the proposed research should not only provide fundamental knowledge regarding translational regulation, but also provide novel molecular targets for modulating sperm production in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MALE INFERTILITY AND ITS BIOLOGICAL BASIS Principal Investigator & Institution: Zirkin, Barry R.; Professor; Population & Family Hlth Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 02-APR-1998; Project End 31-MAR-2004 Summary: This application proposes four integrated projects centered on male infertility and its biological basis. Project I will examine the role of inadequate
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Male Infertility
intratesticular testosterone concentration in human male infertility. The hypothesis that reduced intratesticular testosterone concentration is responsible for some conditions of infertility will be tested directly in infertile men. Project II will examine the mechanism(s) by which testosterone protects germ cells from apoptotic death. A central hypothesis is that testosterone promotes the survival of germ cells via its effects on the Sertoli cell/germ cell Fas system, and through the Bcl- 2 family of cell survival/cell death proteins of germ cells. The results of Projects I and II should elucidate common principles involved in regulating spermatogenesis in rats and men. Project II focuses on how testosterone functions to regulate spermatogenesis through the androgen receptor (AR). The hypothesis will be tested that stage-specific regulation of AR gene expression in Sertoli cells is affected via the differential expression of endogenous transcription factors that bind to the AR promoter and enhance or repress transcription of the AR gene. The hypothesis that the AR is able to recruit endogenous co-regulatory proteins in Sertoli cells, and that these protein-protein interactions activate or repress AR transcriptional activity of genes required during spermatogenesis also will be examined. Thus Project III also provides a link between intratesticular testosterone (Projects I and II) and stage- specific gene expression (Project IV). Project IV examines the interactions between germ cells and Sertoli cells, critical for how spermatogenesis is coordinated and regulated. It will examine the function and regulation of stage-specific gene expression of analyses of Cyclic Protein-2, the pro-enzyme form of the cysteine protease Cathepsin L. It will be determined whether cis-acting elements in the CP-2/Cathepsin L gene and trans-acting factors in Sertoli cells interact in a stage- specific manner; and whether these regions are responsible for stage- specific transcription of the CP-2/Cathepsin L gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICRO-ASSISTED FERTILIZATION/GENETIC DEFECTS Principal Investigator & Institution: Lamb, Delores J.; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002 Summary: While the problem of female infertility has been a focus of scientific political, and media attention, abnormalities in the male account for 30- 50% of all infertile cases, yet has received little attention. Most cases of male infertility are a consequence of too few or abnormal sperm, yet the factors that contribute to the problem are unknown. As a result, relative little effective therapy has been established for the male with impaired sperm production. The development of intracytoplasmic sperm injection (ICSI) with in vitro fertilization (IVF) has improve our ability to use suboptimal semen specimens to produce conceptions. ICSI has been used to achieve pregnancies for patients with genetic causes of infertility and for axoospermic patients with severe spermatogenic defects by testicular sperm extraction (TESE). It is likely that many types of "idiopathic" infertility are actually due to genetic defects. In this translational project, we will test the hypothesis that genetic instability is present in the testis of some axospermic candidates for TESE-ICSI. This will be examined at the constitutional chromosomal level using high resolution banding cytogenetics and fluorescent in situ hybridization (FISH) and at the level of specific nucleotides using microsatellite instability and Y chromosome deletion intervals. We propose to evaluate the safety of game micromanipulation in human IVF. Clinical and genetic assessment of each subfertile man and long-term genetic and developmental ealaut8ion of the children resulting from micromanipulation will be performed. The results of these studies will be evaluated in association with state-of-theart clinical and molecular laboratory examination of the male that is necessary for proper patient classification. We propose that molecular characterization of patients
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may provide the most important insights into ICSI outcomes. Finally, we will use neural computation to model ICSI outcomes derived from this proposal. Our long-range goal is to develop a safe and effective treatment for the infertile male patient. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF MALE INFERTILITY Principal Investigator & Institution: Lamb, Dolores; Associate Professor; Urology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 10-MAY-2000; Project End 30-APR-2005 Summary: This application proposes the establishment of a Program Project at Baylor College of Medicine to study male infertility with a focus on investigation the etiology of abnormal sperm production and the application of assisted reproductive techniques to overcome these defects. The Program Project will have as its nucleus a core administrative unit that will coordinate the activities of the basic and clinical scientists on a day to day basis. The focus of this Program Project will be in the area of the molecular biology of male infertility with specific emphasis on defining the genes required for normal spermatogenesis. Assisted reproductive techniques have been used to overcome many male factor defects. It is assumed that if a sperm can fertilize, than it is "healthy". We have no scientific basis for this belief and many of these offspring could be carrying genetic defects. The aims for the proposal are: 1. To establish a program project for the study of male infertility creating a close working relationship between basic and clinical scientists from the Departments of Urology, Obstetrics and Gynecology., Cell Biology, and Medical Genetics. Bring these groups together in one project will create a more effective focus on male infertility than would occur with these scientists working individually. 2. To Create a facility to analyze DNA and perform in situ hybridization represents a significant a significant and critical component of this Program Project. 3. To correlate clinical features of male infertility with new discoveries at the mo level, to better understand the diseases processes and thereby to develop ad more effective treatment and diagnostic modalities. The expertise of this multidisciplinary group of scientists working together is expected to yield new understanding of the basic pathophysiology of male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BASIS OF MAMMALIAN SPERM MOTILITY Principal Investigator & Institution: Strauss, Jerome F.; Professor; Obstetrics and Gynecology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Sperm must be motile following their deposition in the female reproductive tract to fertilize ovulated eggs. Factors that regulate the power stroke and waveform of the sperm flagellum are poorly understood. Although several components of mammalian sperm flagella have been characterized, relatively little is known about proteins comprising the central apparatus in the axoneme core, which are thought to play a major role in controlling flagellar function. The long term goal of this research project is to characterize the regulatory proteins of the mammalian sperm axoneme and to identify their roles in governing flagellar activity. Four specific aims are proposed: 1) To determine the roles of the mammalian homologues of the Chlamydomonas proteins encoded by the PF16 and PF2O in sperm flagellar activity; 2) To generate targeted deletion mutants in mice of the PF16 gene, and later the PF2O gene, to assess their role in flagellogenesis and sperm motility; 3) To characterize the temporal and spatial
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Male Infertility
patterns of expression of PF16, PF2O as well as other proteins during assembly of the sperm axoneme; and 4) To identify interactions among these axonemal proteins using genetic, biochemical and ultrastructural methods. We will examine the ability of antibodies and recombinant proteins to disrupt the function of PF16 and PF2O in reactivated demembranated or permeabilized sperm flagella. The overall hypothesis to be tested is that central apparatus proteins control the microtubule motors through an ordered sequence of protein-protein interactions. The function of PF16 will be probed by targeted deletion of the murine PF16 gene. The anticipated phenotype of the knockout is male infertility due to paralyzed or dysfunctional sperm flagellar activity. The murine model will also allow us to examine the role of PF16 in the maintenance of the structural integrity of the central apparatus. To test the hypothesis that the central apparatus is assembled prior to the formation of other flagellar components including the fibrous sheath, we will define the temporal and spatial patterns of expression of PF16 and PF20 relative to the fibrous sheath protein, AKAP82. Finally, in an effort to gain a more complete understanding-of the proteins comprising the mammalian axoneme, we will identify interacting partners of PF16 and PF2O using the yeast two-hybrid system and alternative biochemical methods. Knowledge gained from these experiments will provide a molecular framework for understanding some sperm motility defects that cause male infertility and possibly offer new avenue for contraception through the disruption of purposeful sperm motion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR CONSEQUENCES OF ICSI
MECHANISM
AND
DEVELOPMENT
Principal Investigator & Institution: Schultz, Richard M.; Professor; Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: The practice of Assisted Reproductive Technology (ART) to overcome infertility in humans has increased dramatically during the past two decades and has culminated in the widespread use of intracytoplasmic sperm injection (ICSI), which can overcome instances of infertility previously thought to be intractable. Due to the inherent difficulty of conducting basic research with the limited amounts of human material and governmental bans on basic research of human eggs and pre-implantation embryos, the development of ART hs occurred essentially in the absence of basic research using an animal model system. In essence, this is an example of ART before science. In this grant application, we propose to use the mouse as a model system to study the molecular mechanism and developmental/behavioral consequences of ICSI. The ability of eggs to be activated by parthenogenetic stimuli increases with the time post-hCG administration and correlates with progression of metaphase II-arrested eggs into an interphase-like state. The first Specific Aim will test the hypothesis that, similar to parthenogenetic egg activation, the success of ICSI-induced egg activation increases with time following hCG administration. While ICSI has clearly revolutionized the treatment of male infertility, the molecular basis of how ICSI activates the egg and initiates the program of early development is poorly understood, especially in light of the fact that ICSI bypasses the normal pathway used by the sperm to fertilize the egg. Understanding the molecular basis of egg activation by ICSI will inevitably yield an understanding as to causes for its failure and rationale approaches to enhances its efficacy. The second Specific Aim will test the hypothesis that ICSI recruits signaling pathways that are normally activated during the course of natural fertilization and results in the normal complement of events of egg activation. The rapidly gaining use of
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ICSI as the method-of-choice to overcome human male infertility has raised a vigorous debate concerning the long-term risk imposed to the resultant offspring. Although it is reassuring at first glance that there is no apparent significant increase in the incidence of gross congenital abnormalities in ICSI-derived offspring, these children are still young and hence more subtle effects that influence behavioral and intellectual development may not yet be apparent. The third Specific Aim will test the hypothesis that mouse ICSI results in subtle developmental and behavior abnormalities in the generated offspring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE GALTRANSFERASE--STRUCTURE/EXPRESSION Principal Investigator & Institution: Shaper, Joel H.; Professor; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 28-FEB-2005 Summary: Glycoconjugates are a major class of molecules found on the surface of all cells including developing male germ cells. Glycans are biosynthesized by the coordinate action of a functional family of membrane-bound enzymes, termed glycosyltransferases. In spite of the diverse role that glycans serve in the proper functioning of a cell, there is a paucity of information on the regulation of glycosyltransferases genes. Using the beta4-galactosyltransferase-I (beta4GalT-I) gene as a "model system" we have shown that during spermatogenesis there is a switch to a male germ cell-specific transcriptional start site that is used exclusively in round spermatids. Furthermore, we have identified a new 14-base pair regulatory motif (the TASS-1 motif) upstream of this start site that is essential for in vivo expression of beta4GalT-I in round spermatids. Coincident with the switch to the male germ cellspecific promoter there is also a switch to the use of one or two alternative, internal poly- adenylation sites. The net result of this switch is the generation of truncated male germ cell-specific beta4GalT-1 mRNAs in which approximately 1.7 kb of the lung (2.5 kb) 3'-untranslated region (3'-UTR) that distinguishes the beta4GalT-I somatic transcript, has been deleted. While the use of an internal polyadenylation site and the consequent truncation of the 3'-UTR is an emerging general paradigm for genes expressed in both somatic and male germ cells, the biological significance of this truncation is unknown. In this proposal we have four complementary goals. First, the TASS-1 will be characterized at the protein level, to determine if it is a novel member of a known family of transcription factors or defines a new family of transcription factors. Third, transgenic mouse lines in which the TASS-1 gene has been inactivated by homologous recombination will be analyzed to determine the consequences on male germ cell development. Fourth, we will test the hypothesis that the truncation of the consequences on male germ cell development. Fourth, we will tet the hypothesis that the truncation of the 3'-UTR results in male germ cell-restricted beta4GalT-1 transcripts with increased stability, relative to that of the somatic transcript. Assays using transfected 3'UTR/reporter gene constructs and transgenic analysis will be used to examined mRNA stability both in vitro and in vivo. This proposal offers the potential to identify and characterize a new family of transcription factors essential for male germ cell development, and provide insight as to why germ cell transcripts contain truncated 3'UTRs relative to their somatic cell counterparts. Consequently, it impacts only on male germ cell development but also on male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Male Infertility
Project Title: NOVEL CATSPER3 AND CATSPER4 ION CHANNEL GENES IN SPERM Principal Investigator & Institution: Clapham, David E.; Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The fusion of sperm and egg lead to the combination of the father's and mother's genetic information to create a new individual. In humans, as in all mammals, sperm must reach the egg, penetrate its protective coat, fuse with the oocyte membrane, and deliver its genetic material. Ion channels in the sperm mediate many of these steps. We have identified four ion channels that are in sperm but not other tissues. CatSpers (Cation channel of Sperm) are six transmembrane-spanning ion channel proteins localized primarily to the tail of mature sperm (Ren et al, 2001). CatSper1 is an ion channel that triggers calcium-influx into the principal piece of the sperm tail. Male mice homozygous for null-mutations in the CatSper1 gene are 100% infertile, but otherwise are completely normal. Sperm from mice genetically engineered to lack the functional CatSper1 gene show a significant reduction in motility and are incapable of penetrating through the outer coat of an egg. We have identified two new sperm-specific proteins, CatSper3 and CatSper4 that are localized to the sperm tail. Experiments are proposed that will delineate the function of these novel ion channels and reveal their role in sperm function. Understanding these proteins will increase our understanding of fertilization and shed light on both some causes of male infertility as well as provide new targets for contraceptive agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PITUITARY CELLS TO STUDY MALE INFERTILITY Principal Investigator & Institution: Winters, Stephen J.; Chief; Medicine; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-APR-1986; Project End 30-JUN-2004 Summary: As many as 15 percent of couples are evaluated at some time for a fertility disturbance. Of these, 40 percent are male factor infertility, and in another 20 percent the infertility is unexplained. Evidence that sperm counts have declined substantially in the twentieth century adds further significance to research in male reproductive health. The long term goal of this project is to understand the endocrine aspects of human male infertility by analyzing the mechanisms involved in the testicular control of gonadotropin secretion. Most of what is known about the cellular and molecuar biology of gonadotropin secretion is from experiments using rats and rat pituitary cells. But our research indicates that the control mechanisms regulating gonadotropin secretion in male rats may not always be applicable to men. Herein we propose the use of pituitary cell cultures from the nonhuman male primate as a model of the human hypothalamicpituitary unit in an effort to understand gonadotropin secretion in normal and infertile men. Experiments will be conducted using monolayer cultures as well as perifused pituitary cells stimulated with pulses of GnRH. The major endpoints to be examined include gonadotropin secretion and subunit gene expression, GnRH receptors and follistatin mRNA. The aims of the current proposal are: 1) To examine the effects of recombinant inhibin-B and recombinant inhibin-A in the presence or absence of activinA on gonadotropin secretion and subunit gene expression in primate pituitary cells, 2) To determine whether GnRH pulse frequency differentially regulates the secretion of FSH and LH in perifused primate pituitary cells, and to probe the role of activin, inhibin and follistatin in this regulation, and 3) To determine why estradiol but not androgens
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inhibit gonadotropin secretion in primate pitutiary cells. The information to be derived from these studies should provide insight into the endocrine abnormalities in human male infertilty which cannot be learned from studies in cell lines or rats, or through human investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION SPERMATOGENESIS
OF
GENE
EXPRESSION
DURING
Principal Investigator & Institution: Petrusz, Peter; Cell and Developmental Biology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Androgens are indispensable for normal spermatogenesis; however, the mechanism by which androgens exert their effect on this complex process is poorly understood. Androgens act on their target cells by binding to and activating the androgen receptor (AR) present in Sertoli cells, peritubular cells, and Leydig cells but not in germ cells. It is assumed that androgens' actions on spermatogenesis are mediated by paracrine signals resulting from changes in gene expression in Sertoli and peritubular cells. In spite of an intensive research effort for several decades, traditional methods have failed to pinpoint key androgen-regulated genes whose activation is critical for spermatogenesis. We have studied a transgenic mouse model that overexpresses androgen-binding protein (ABP), a secretory product of Sertoli cells. These transgenic animals develop a progressive impairment of spermatogenesis and become gradually infertile. The results of our morphological, immunocytochemical, and flow cytometric analyses of the testes indicate that the most likely cause of this impairment is the reduction in the concentration of bioavailable androgens in the peritubular compartment and the seminiferous tubules. DNA microarray technology offers a novel and powerful means to analyze gene expression in a comprehensive, yet efficient, way. The Specific Aim of this pilot project is to test the hypothesis that the chronic reduction of bioavailable androgens within the seminiferous tubules of the ABP-transgenic mice is manifested in ordered changes in gene expression detectable by DNA microarray analysis. Murine genome oligonucleotide arrays will be probed by cRNAs prepared from testes of wild type and transgenic mice of 30 days of age. As additional controls, a set of the transgenic animals will be treated with human chorionic gonadotropin. This treatment is known to increase intratesticular androgen concentration and should reverse the changes caused specifically by androgen depletion. Results will be analyzed in terms of expression levels, expression profiles (dendrograms) and functional relationships. Cellular localization of altered gene expression will be determined by in situ hybridization and immunocytochemistry. This strategy is likely to provide, for the first time, a comprehensive view of androgendependent genes in the mammalian testis, offering a rich source of information for further studies, new clues for understanding and treating certain cases of human male infertility, and new potential molecular targets for male contraception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SPERMIOGENESIS IN MICE Principal Investigator & Institution: Wang, Peijing J.; Animal Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008
42
Male Infertility
Summary: (provided by applicant): The broad, long-term objective of the present application is to study a novel regulatory pathway of gene expression in mouse spermiogenesis that could be exploited for development of novel male contraceptives. Spermiogenesis is a complex differentiation process by which haploid germ cells transform into mature spermatozoa. In the past few years, genetic studies in mice have identified four genes that cause a global arrest in early spermiogenesis when deleted in mice, and these genes constitute a group of key regulators of spermiogenesis (CREM, TRF2, MIWI, and TPAP). In this project, we will characterize a novel key regulator of spermiogenesis named RNF17 in mice. Our specific aims are: 1) Knockout mice will be generated and characterized to study the regulation of spermiogenesis; 2) Proteins interacting with the novel key regulator will be screened using the yeast 2-hybrid system, and will be characterized biochemically and cell biologically; 3) Genes transcriptionally regulated by the novel key regulator will be identified by the gene array technology using both the Affymetrix mouse gene chips and our own germ cell microarrays. Our proposed genetic, biochemical and genomics experiments will define a novel regulatory network of gene expression in mouse spermiogenesis, will have implications in molecular etiology of male infertility in humans, and will provide critical information about regulation of spermiogenesis that could be explored for developing reversible male contraceptive leads with minimal side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELEASE AND MOLECULAR COMPOSITION OF MAMMALIAN SFS Principal Investigator & Institution: Fissore, Rafael A.; Veterinary and Animal Sciences; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Fertilization in mammalian eggs is characterized by the presence of intracellular calcium ([Ca2+]i) oscillations that are responsible for inducing egg activation. How the sperm initiates and sustains these oscillations is not known, although recent evidence, including that from intracytoplasmic sperm injection experiments (ICSI), suggests that the sperm may release into the ooplasm, after fusion, a [Ca2+]i oscillation-inducing factor (SF). The long-term goal of the laboratory is to isolate and purify the sperm's Ca 2+ active molecule, and the present specific aims will ascertain the temporal release and cellular targeting of SF and the molecular composition of the different Ca 2+active fractions in sperm. Specific Aim 1: To investigate the temporal release of SF. The hypothesis will be examined that SF becomes rapidly dissociated from the sperm head to induce persistent oscillations and then, at the time of pronuclear (PN) formation, it associates with pronuclear (PN)/peri-PN structures, the targeting for which is received at the time of release. To test this hypothesis, Hoechst-labeled sperm heads will be removed from fertilized eggs, and the persistence of oscillations in these eggs monitored in the presence of colcemid. Association of SF with the PN in enucleated eggs will be evaluated by the presence of a [Ca2v]i rise at PN-envelope breakdown, which will be induced by exposure to okadaic acid. Specific Aim 2: To investigate the molecular composition of the different sperm Ca 2+ active preparations. The hypothesis will be studied that distinct sperm Ca 2+ active fractions, i.e. soluble SF and less soluble (Triton X-100 and pH-soluble) SFs, share biochemical properties and may have, in fact, a common Ca 2v active molecule(s). Biochemical fractionation will be carried out using column chromatography, and affinity precipitation using biotinylated peptide A7, which depletes Ca 2v activity from SF. Sequencing of significant polypeptide bands will be performed after SDS-PAGE by
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Matrix Assisted Laser Desorption-Mass Spectrometry. The presence and function of phospholipase C (PLC) zeta, a novel testis PLC, will be assessed by Western blotting and depletion of the molecule from the fractions. Significance: 1) Results from these aims will provide the first description of temporal release of SF during fertilization, and will establish the polypeptide composition of all the Ca 2vactive preparations in sperm, which will lead to the identification of SF; 2) It will be possible to assess the physiological relevance and impact of sperm manipulations on the pattern of oscillations initiated by ICSI, a technique commonly used to treat human male infertility, which has been shown to have detrimental effects on development, and some of which may be due to activation defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REMODELING OBSTRUCTION
OF
MALE
TRACT
EPITHELIA
AFTER
Principal Investigator & Institution: Turner, Terry T.; Professor; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2003 Summary: Obstruction of the male reproductive tract can occur for several reasons, e.g. infection, trauma, congenital defects, and vasectomy. The most common cause of male tract obstruction is vasectomy. Obstruction can theoretically have effects either proximal to or distal to the obstruction site. Most Studies of the effects of obstruction have been on the tract proximal to the obstruction (testis and epididymis) and have focused on the testis because of its important spermatogenic and steroidogenic functions. Studies of the epididymal response to obstruction have been fewer, and none have studied the in vivo capacity of the epididymal epithelium to carry out complex, but quantitiatable cell tasks while under the influence of the obstruction. Neither has it been determined whether cell functions altered under the influence of obstruction return to normal after surgical relief of obstruction. Such information is important to our understanding of the male infertility which persists after the clinical reversal of duct obstruction, whether from vasectomy or other causes. In this application we proposed to use the rat model to determine the influence of duct obstruction on epididymal protein synthesis and luminal secretion in vivo, and to determine whether detected changes are eliminated by surgical reconstruction of a patent duct. Studies of the effects of duct obstruction distal to the site of obstruction are few, but residual concerns about the connection between vasectomy and prostatic cancer make it important to carefully determine the effects of ductal obstruction on the prostate. We propose to study the effects of vas deferens obstruction on the adult and study the effects of vas deferens obstruction on the adult and prepubertal prostate by measuring general parameters such as prostatic wt and total protein and DNA content, and by assessing the ability of the prostate to synthesize proteins and to secrete proteins into the glandular lumen in vivo. Changes detected after ductal obstruction will open opportunity to further studies into the mechanism of such changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPRODUCTIVE BIOCHEMISTRY OF TESTIS-SPECIFIC LDH-X Principal Investigator & Institution: Goldberg, Erwin; Professor; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-DEC-1977; Project End 29-FEB-2004
44
Male Infertility
Summary: To understand the complexity of spermatogenesis it is necessary to examine the details of gene expression and ultimately correlate these with the multiplicity of morphological and biochemical changes which occur as spermatogonia differentiate into spermatozoa. The gene encoding testis-specific lactate dehydrogenase (ldh-c) uses a promoter not transcriptionally active in somatic cells. Ldh-c expression begins during prophase of the first meiotic division. A transgene consisting of an 100 bp ldh-c core promoter (murine) and lacZ, expressed beta- galactosidase only n pachytene spermatocytes from male offspring of founder mice. The murine ldh-c promoter contains a dual function palindrome sequence required for transcriptional initiation in germ cells and repression of gene expression in somatic tissues. There are several ubiquitous cis-regulatory elements as well as testis specific protein -DNA binding. We can determine the roles played by testis specific and non-specific transcription factors in regulating this gene. This in turn will allow us to select transcription factors as targets in reverse genetics experiments that should enhance our understanding of the molecular events involved on the path from stem cell to spermatozoan. To accomplish this we propose the following specific aims: (1) to study transcriptional regulation of ldh-c by deletion analysis of upstream sequences in transgene constructs. Selected protein binding sequences of the murine ldh-c promoter will be used as "bait" in the "yeast onehybrid" system for transcription factor capture, cloning, identification and isolation; (2) to use genetically engineered mice as model systems for the study of transcription by expressing regulatory motifs as transgenes; (3) to disrupt the endogenous ldh-c gene locus by homologous recombination and thereby eliminate LDH-C4 synthesis in transgenic mice; and (4) to down-regulate transcription factor expression in primary spermatocytes with ribozyme transgenes expressed under control of the ldh-c promoter. These goals are important for understanding specific gene expression. They will take us to the next level to analyze signal transduction pathways involved in sperm cell: supporting cell interactions. Ultimately, these data will permit us to fully realize the potential of gene therapy in alleviating male infertility and for fertility control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF BCL-X IN MURINE SPERMATOGENESIS Principal Investigator & Institution: Rucker, Edmund B.; Animal Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 02-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Apoptosis, or programmed cell death, is a biochemical process that is mediated by a concert of cellular proteins including receptor "initiators" (e.g., TNFR tumor necrosis factor receptor superfamily), the mitochondrialassociating Bcl-2 family "mediators" (e.g., Bcl-2, Bax, Bcl-XL), and the protease "executioners" (e.g., caspases). Spermatogenesis can be blocked by the overexpression or deletion of these apoptosis-related genes, leading to male infertility or sterility. For example, ectopic expression of Bcl-2 and Bcl-x in transgenic mice inhibits apoptosis of spermatogonia and causes infertility. In addition, Bcl-x is expressed in the mouse and human testis within spermatogonia and spermatocytes. Due to the embryonic lethality associated with the bcl-x null mutation, it has not been possible to ascertain the role of Bcl-x in gamete development. Preliminary data support the hypothesis that Bcl-x is required to maintain the survival of spermatogonia and spermatocytes during murine spermatogenesis. To address this hypothesis the following specific aims are proposed. Specific Aim 1: Determine whether Bcl-x maintains the survival of spermatogonial cell populations in the mouse testes. To do this, we ablate the bcl-x gene in murine spermatocytes using the Cre-lox system. This approach will reveal the role of Bcl-x in
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spermatocyte survival in the mouse testis. Specific Aim 2: Determine whether Bcl-x and Bax are antagonists in the fate determination of the spermatogonial cell populations in the mouse testes. To do this, we will generate double mouse mutants that lack both the bcl-x and bax genes derived from Cre-lox (bcl-x) and conventional (bax) gene knockout strategies. Resultant mutants will demonstrate whether Bcl-x and Bax compete in determining the apoptotic fate of spermatocytes during murine spermatogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF SPECIFIC PROTEINS IN SPERMATOGENESIS Principal Investigator & Institution: Kistler, W Stephen.; Professor; Chemistry and Biochemistry; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2003; Project Start 01-APR-1976; Project End 29-SEP-2003 Summary: Our long term goal is to understand the functional roles and the factors that regulate the developmental appearance of several novel chromosomal proteins that are common features of mammalian spermatogenesis. During the pachytene stage of meiosis a set of novel variants for all the common histones except H4 replace to varying degrees their somatic-type counterparts. Perhaps the most unusual testis histone variant is H1t, whose primary structure differs from standard H1 proteins throughout much of its length. Because H1 is the histone class responsible for determining the compaction of nucleosomal DNA, H1t may well impart an unusual structure to late meiotic and postmeiotic chromosomes. Later, in condensing spermatids, most or all of the histones are replaced with sperm-specific chromosomal proteins, so that these testis-specific histone variants are scarce or absent in spermatozoa. Presumably the unusual histone variants of spermatogenesis play some role ensuring that meiotic events, spermatid development, and chromosome organization in the sperm occur appropriately. Information about the function and regulation of these proteins, and H1t in particular, could lead to better assessment of some forms of male infertility, the identification of causes of chromosomal abnormalities and failures of early development and a better understanding of chromosomal structure and gene regulation in general. Experiments are planned to assess the functional importance of H1t by using targeted gene disruption in embryonic stem cells to make an H1t knockout mouse. If spermatogenesis is affected, the same technique will be used to substitute a somatic H1 for H1t and thus determine whether H1t's unique structure is important. To understand the transcriptional mechanisms that account for the complete silence of the H1t gene in somatic cells but its expression in late spermatocytes, we will clone and characterize a testis-specific binding factor for a conserved palindrome in the Hlt promoter. It is expected that eventual study of the promoter for this apparent transcription factor will lead to better understanding of how the process of spermatogenesis is driven forward. the H1t gene is repressed in rodent cell lines by a G/C-rich region just downstream of its TATA box. We will attempt to identify the factor(s) responsible for repression. Transgenic mice will be used to analyse the effect of mutations in the conserved Hlt palindrome and the repressor element downstream of the TATA box. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF VEGF IN TESTIS DEVELOPMENT AND FUNCTION Principal Investigator & Institution: Cupp, Andrea S.; Animal Science; University of Nebraska Lincoln Lincoln, Ne 685880430 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005
46
Male Infertility
Summary: (provided by applicant): Formation of the seminiferous cords, the precursor seminiferous tubules, is the first morphological event that distinguishes the testis from the ovary. The cords contain Sertoli and germ cells surrounded by peritubular cells. Sry expressed in the Sertoli cell induces mesonephric cell migration into the differentiating testis to form cords. If the mesonephros is removed, or mesonephric cell migration is blocked, no cord formation occurs. One cell type that migrates to the testis during cord forrnation is the endothelial cell. Therefore, angiogenic factors involved in vasculature development may also be critical for cord formation. The long-range goal of this research is to elucidate cellular and molecular mechanisms regulating angiogenesis and morphological sex determination (cord formation) in the testis. The objective of this proposal, the first step toward attaining our long-range goal, is to identify angiogenic factors that induce mesonephric endothelial cell migration and determine if these factors are participating in both vascular development and cord formation. Preliminary experiments, in our laboratory, have established that one angiogenic factor, Vascular Endothelial Growth Factor (VEGF), and its receptor VEGFR-2 are present at the time of cord formation in cells that direct testis differentiation. Furthermore, preliminary data from our lab have determined that signaling antagonists to VEGF receptors inhibit cord formation. Therefore, the central hypothesis of this proposal is that VEGF and VEGFR-2 are involved in both vascularization and cord formation in the testis. To test the hypothesis and accomplish the overall objective of this application two specific aims are proposed: 1) Determine the mechanisms of VEGF and VEGFR-2 action on cord formation and vascular development during testis morphogenesis; and 2) Investigate the functional effects of VEGF isoforms on endothelial cell migration during testis morphogenesis. Altered regulation of either VEGF or VEGFR-2 may result in abnormal testis differentiation resulting in infertility. The current proposal seeks to fill the gaps in our current knowledge of how VEGF and VEGFR-2 may regulate testis morphogenesis to gain a better understanding of male infertility problems occurring through abnormal testis differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SOMATIC CELLS AND SPERMATOCYTE MAINTENANCE IN DROSOPHILA Principal Investigator & Institution: Dinardo, Stephen; Professor; Anatomy; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: The incidence of testicular cancers and of male infertility is increasing. Insight into the cellular causes of this can only come with a systematic understanding of the regulatory pathways governing spermatogenesis. In order to generate functional sperm, several diverse cellular processes are coordinated during spermatogenesis. These processes include the growth and maturation of spermatocytes, which occurs in close association with surrounding somatic cells, suggesting that soma-germline communication is involved. This proposal focuses on spermatogenesis in Drosophila, which is similar to that in mammals, and in which genetic analysis provides a way to systematically dissect the signals necessary for spermatocyte development. The transcriptional activator Eyes absent (Eya) is expressed in somatic cyst cells where it is required for the maintenance of encysted spermatocytes. Sine oculis (So), a homeodomain protein that appears to act in a transcriptional regulatory complex with Eya, is also required for spermatocyte maintenance. The hypothesis to be tested is that an Eya/So-dependent signal from cyst cells is required for spermatocyte development. The role of Eya/So in cyst cell fate and behavior will be assessed. In addition, the stage
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at which Eya and So affect spermatocyte development will be defined. Next, the ectopic expression of Eya and So will test whether the Eya/So-dependent signal is permissive or instructive. Complementary approaches, including the analysis of 40 spermatocyte degeneration mutants and a genetic screen for suppressors, will attempt to identify the signal from somatic cells, or components of its response in spermatocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECTROMICROSCOPY FOR BIOCHEMICAL ANALYSIS OF SPERM Principal Investigator & Institution: Jacobsen, Chris J.; Professor; Physics and Astronomy; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Description (provided by applicant): We propose to develop the capabilities of x-ray spectromicroscopy to allow it to be applied to biochemical imaging of normal and abnormal sperm. This will be done by focusing "soft" X rays (in this case, x rays with a photon energy of 200-800 eV) to the smallest far-field focus of electromagnetic radiation of any wavelength, and scanning a dry or frozen hydrated specimen through that focal spot to form an image. Images at a series of photon energies will then be combined to deliver chemical-state-sensitive x-ray absorption spectra from an entire sperm at better than 50 nm spatial resolution. From this data, major biochemical constituents in individual sperm will be determined by fitting to reference spectra of isolated compounds; furthermore, expected and possibly unexpected spatial correlations between components will be studied using principal component analysis methods. This work will be carried out using x-ray microscopes developed by our group at Stony Brook which operate at a soft x-ray undulator beamline at the National Synchrotron Light Source at Brookhaven National Laboratory. The microscopes will be improved by the addition of better order sorting optics for quatitative spectroscopy, and by equipping a cryo microscope with a more accurate piezo stage and a higher efficiency detector for studies of frozen hydrated specimens without excessive radiation damage. These instrumentation developments will be guided by our goal of studying the correlation between morphological and biochemical variations in sperm, in order to better understand the causes of male infertility. By obtaining x-ray spectromicroscopic data on different sperm morphologies in infertile males, we hope to guide the in vitro fertilization (IVP) clinician in the choice of sperm use for intracytoplasmic sperm injection (ICSI) so as to improve the success rate of the procedure. Spectromicroscopic data anaysis software will be made available for free downloading by other researchers as it is developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPERMATOGONIAL TRANSPLANTATION
STEM
CELL
CULTURE
AND
Principal Investigator & Institution: Brinster, Ralph L.; Professor of Physiology; Animal Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: We have developed a method that allows transfer of testicular cells from a fertile male to the seminiferous tubules of an infertile male. Following transfer, the donor cell population establishes normal spermatogenesis in the recipient testes, and mature spermatozoa are produced and found in the epididymis. In the most successful transplantations, the recipient male becomes fertile, and the donor cell haplotype if found in progeny of the male. We have used this approach to demonstrate that
48
Male Infertility
spermatogonial stem cells can be cryopreserved, thus making individual male germ lines immortal. In addition, transplanted rat testis cells will generate spermatogenesis in the seminiferous tubules of immunodeficient mice and produce rat spermatozoa, suggesting that xenogeneic spermatogenesis may be possible for other species. This testis call transplantation technique provides an opportunity to perform experiments with male germ cells that previously were difficult or impossible. In this project, we have three specific aims. 1. To increase the efficiency with which donor cells colonize and repopulate the seminiferous tubules of recipient mice. 2. To grow in vitro and expand the number of the testicular stem cells responsible for repopulating the recipient testis. 3. To modify the genetic characteristics of spermatogonial stem cells and recover the new haplotype in progeny. The studies proposed will make spermatogonial transplantation useful for a wide range of applications in biology, medicine and agriculture. In addition, the knowledge gained will help alleviate certain forms of male infertility and help in the development of new contraceptive approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROIDOGENIC ENZYME CHANGE AFTER TNFA & LEPTIN EXPOSURE Principal Investigator & Institution: Watson, Angela M.; Jackson State University 1400 John R. Lynch St Jackson, Ms 39217 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-DEC-2005 Summary: Many changes occur in experimental animals (ob/ob mice) as a result of obesity. The ob/ob mice have been shown to be diabetic and have an increased level of insulin as well as corticosterone (Uysal et al., 1997). Others have also shown that there is an increased level of the cytokine, TNF-alpha, in the serum of these mice (Hotamisligil, 1993) which has been shown to cause a decrease in the level of testosterone in vitro (Xiong and Hales, 1993a). Regulation and expression of certain steroidogenic enzymes such as CYPO17c and CYPscc have been shown to be decreased following in vitro exposure of mouse Leydig cells to TNF-alpha. Changes in the steroidogenic enzymes may lead to decreased levels of testosterone which could ultimately affect the sterility of these animals. In this study, several protocols have been proposed that will be utilized to elucidate the mechanism by which TNF-alpha causes reduction of certain steroidogenic enzymes. The hypothesis of this study is that the increase in TNF-alpha, secondary to obesity, may cause a reduction in the levels or activity of some or all of the steroidogenic enzymes producing a decrease in testosterone production. A prolonged decrease in testosterone levels or production may affect spermatogenesis and thus contribute to male infertility or subfertility. Specifically, I propose the following: 1) To determine the changes in steroidogenic enzymes following the treatment of lean and ob/ob mice with TNF- alpha; 2) To determine the changes in steroidogenic enzymes following the treatment of lean and ob/ob mice with pentoxyfilline and antibodies directed to TNF-alpha; and 3) To determine the changes in steroidogenic enzymes in TNF-alpha receptor (both receptors) knockout ob/ob mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYMPOSIUM:MEN'S HEALTH ISSUES IN BASIC UROLOGIC RESEARCH Principal Investigator & Institution: Kyprianou, Natasha; Director; Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 27-DEC-2001; Project End 26-NOV-2002
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Summary: provided by applicant): The Society for Basic Urologic Research (SBUR) 11th Fall Annual Symposium 2001, will be held in conjunction with the 4th World Congress in Urologic Research, on November 29-December 2, 2001 at the Lowes Ventana Canyon Resort, in Tucson, Arizona. The theme of this international meeting is "Men's Health in Basic Urologic Research". The purpose of the conference is to provide a forum for the dissemination and discussion of basic and clinical research in the context of the pathophysiology and treatment of male urologic diseases. The meeting has been designed to integrate the recent basic research efforts of international experts with the clinical perspective of leading investigators in the field. The meeting will attract investigators currently working on molecular, genetic, or clinical aspects of the various urologic conditions associated with men, as well as researchers interested in learning more about the field, or wishing to contribute their own expertise and share their recent findings. The conference is organized to be an updated broad survey of the application of current basic understanding in the study of pathophysiological conditions associated with the genitourinary tract in men. To reach this goal, eight scientific sessions will explore the following themes: 1) Androgens; 2) The Androgen Receptor; 3) Male Infertility; 4) Basic Understanding of Male Sexual Function; 5) Cellular Deregulation in the Pathogenesis of Benign Prostatic Hyperplasia and Urinary Obstruction; 6) Molecular Pathways in the Pathogenesis and Treatment of GU Cancers (prostate, kidney, bladder and testes); 7) Urinary Incontinence; and 8) Inflammatory Conditions in Urologic Disease. All participants will have the opportunity to submit abstracts, which will be evaluated by the organizing committee for presentation at poster discussion sessions. Poster sessions will be held as independent events to foster productive intellectual interchange by all participants. Competition for travel awards will be an important component of the meeting to foster the inclusion of young investigators. Funding is requested to partially defray the travel and lodging costs fore the invited speakers and to partially cover the costs of travel awards to young investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF RET IN SPERMATOGENESIS Principal Investigator & Institution: Naughton, Cathy K.; Urology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The two objectives of this application are to support my training as a physician-scientist and to establish the importance of RET tyrosine kinase and its coreceptors and ligands in spermatogenesis. This award will facilitate my transition into an independent investigator by providing molecular laboratory training under the mentorship of Dr. Jeffrey Milbrandt, Professor of Pathology and Immunology and Internal Medicine at Washington University School of Medicine. Dr. Milbrandt is ideally suited to be my mentor for several reasons. His laboratory has significant experience in studying RET, its coreceptors and ligands and has all the available resources, including mouse models, antibodies, probes, etc., already in place to facilitate successful completion of the proposed application. He has previously served as research mentor to eight, K08 recipients in the past 10 years. I will receive continuity of training, as I have previously worked in his laboratory for three years. A didactic program in molecular biology will complement the intellectual environment provided by Dr. Milbrandt's laboratory, the Siteman Cancer Center Developmental Biology Research Meetings, and the Division of Urologic Surgery Research Conferences. The importance of RET, its coreceptors and ligands in spermatogenesis is evidenced by testis expression studies, abnormalities in spermatogenesis of mouse models with mutations of the RET
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Male Infertility
receptor, and loss of RET protein expression in human cases of maturation arrest and male infertility. Maturation arrest is a cause of male-factor infertility due to failure of existing testicular germ cells to mature. Presently, there is no therapy for these patients, and the only potential option for these couples for their own biological children is in vitro fertilization with intracytoplasmic sperm injection. Identification of the component(s) responsible for continued sperm maturation in these men is first necessary in order to target future therapies to facilitate sperm maturation in vivo. The specific aims of this proposal will explore the role of RET in spermatogenesis to determine if signaling through RET is important for germ cell survival, proliferation, and/or maturation. This will be accomplished by studying the disturbed spermatogenesis identified in a mouse model carrying a mutation of the RET receptor. The translation to human disease will be achieved by studying RET expression in male infertility cases of maturation arrest. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE SPECIFIC EXPRESSION AND FUNCTION OF ME-RABP Principal Investigator & Institution: Orgebin-Crist, Marie-Claire; Professor; Obstetrics and Gynecology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-MAY-2004 Summary: In the epididymis spermatozoa mature, gain the ability to fertilize in vivo and are stored prior to ejaculation. Vitamin A is important in epididymal function since it is required to maintain epithelial structures. Targeted mutation of the retinoic acid receptor alpha (RARalpha) results in squamous metaplasia of the epididymal epithelium with resulting infertility (1). The retinoids being hydrophobic labile compounds are transported in a aqueous environments bound to specific carrier proteins. We have found that the epithelium of a restricted region of the epididymis (distal caput) secretes an androgen dependent retinoic acid binding protein (E-RABP) in the lumen of the epididymal duct. We have cloned, sequenced and localized on chromosome 2 the murine E-RABP gene. We have shown that 5 kb of the 5'flanking region ligated in front of the CAT reporter gene targets a surprisingly high level of gene expression in the caput. Our hypothesis is that mE-RABP is essential for the homeostasis and trafficking of retinoids within the epididymis and that its region-specific expression is determined by epididymal transcription factors. Our goals are to establish transgenic mouse models 1) to identify and characterize the minimal sequences conferring region specificity to mE-RABP gene expression and 2) to disrupt mE-RABP gene expression to determine the function of the mE-RABP protein. The specific aims of this study are: 1) To determine the role of the androgen receptor in the region-specific expression of the mE- RABP gene within the epididymis. 2) To identify the regulatory elements and their associated binding proteins involved in the epididymis-and region-specific expression of the mE-RABP gene. 3) To determine the function of mE-RABP using deletion and substitution variants of the mE- RABP gene in transgenic mouse models. Completion of the project will provide valuable tools for future studies designed to probe epididymal function. The mE-RABP promoter can be used to disrupt in vivo other epididymal genes allowing one to analyze the functional role of these genes in the epididymis. The mERABP knock-out mice can be used to re- express mE-RABP in an ectopic site (cauda or vas deferens), allowing one to determine the functional importance of region-specific gene expression in the epididymis. This proposal is part of our long-term goal to understand the mechanisms by which the gene expression in the epididymis. This proposal is part of our long-term goal to understand the mechanisms by which the epididymis provides the optimal milieu for male gametes and contributes to the
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production of a fertile ejaculate. The ultimate goal is to provide the basic knowledge for the rational treatment of some forms of male infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSLATIONAL SPERMATOGENESIS
CONTROL
DURING
MURINE
Principal Investigator & Institution: Braun, Robert E.; Associate Professor; Genome Sciences; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-JAN-2005 Summary: The production of gametes in mammals is an elaborate process that begins during embryogenesis and continues during the reproductive life of the organism. Gametogenesis involves the production of highly specialized cells with unique organelles designed to accomplish the union of sperm and egg at fertilization. The timely production of developmentally important products involves the regulated translation of mRNAs that have accumulated earlier during gametogenesis. Deviation from the wild-type timing of translation can cause cessation of gametogenesis and lead to sterility in mice. Loss of posttranscriptional control may be responsible for a significant percentage of idiopathic male infertility in humans. Our understanding of the genetic control and molecular mechanisms of posttranscriptional control during gametogenesis is woefully incomplete. The long-term goal of this proposal is to elucidate the mechanisms of translational control during spermatogenesis. The knowledge gained from these studies may be useful in the genetic assessment of male infertility in humans, and lead to the development of male contraceptives designed to disrupt essential regulatory steps during normal spermatogenesis. Our studies will focus on the regulation of the spermatid-specific protamine mRNAs. Transgenesis will be used to test specific models for the function of previously identified regulatory sequences in the protamine I, Prm1, 3' untranslated region. A screen will be performed to identify new genes that regulate the translational repression of Prm1 in round spermatids. Mutation of the Prbp gene results in defects in the translational activation of the protamine mRNAs in elongated spermatids and cause male sterility. DNA arrays will be screened to determine the specificity of the Prbp mutant phenotype. Several approaches will be used to pursue the role of PRBP in translational activation. Lastly, targeted mutagenesis will be used to investigate the function of murine Y box proteins in posttranscriptional control. 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, 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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and type “male infertility” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for male infertility in the PubMed Central database: •
A Novel Functional Role for Apolipoprotein B in Male Infertility in Heterozygous Apolipoprotein B Knockout Mice. by Huang L, Voyiaziakis E, Chen HL, Rubin EM, Gordon JW.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38255
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Hydrocephalus, Situs Inversus, Chronic Sinusitis, and Male Infertility in DNA Polymerase [lambda]-Deficient Mice: Possible Implication for the Pathogenesis of Immotile Cilia Syndrome. by Kobayashi Y, Watanabe M, Okada Y, Sawa H, Takai H, Nakanishi M, Kawase Y, Suzuki H, Nagashima K, Ikeda K, Motoyama N.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133740
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Male Infertility, Impaired Sperm Motility, and Hydrocephalus in Mice Deficient in Sperm-Associated Antigen 6. by Sapiro R, Kostetskii I, Olds-Clarke P, Gerton GL, Radice GL, Strauss III JF.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134010
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Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1. by Firestein R, Nagy PL, Daly M, Huie P, Conti M, Cleary ML.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150957
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Overexpression of the Matrix Metalloproteinase Matrilysin Results in Premature Mammary Gland Differentiation and Male Infertility. by Rudolph-Owen LA, Cannon P, Matrisian LM.; 1998 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25271
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Targeted Gene Disruption of Hsp 70-2 Results in Failed Meiosis, Germ Cell Apoptosis, and Male Infertility. by Dix DJ, Allen JW, Collins BW, Mori C, Nakamura N, Poorman-Allen P, Goulding EH, Eddy EM.; 1996 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39594
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 male infertility, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “male infertility” (or 6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for male infertility (hyperlinks lead to article summaries): •
A comparative study on interrelations among microelements, infection of Ureaplasma urealyticum, and male infertility. Author(s): Han XD, Wang Y, Chen JX. Source: Archives of Andrology. 2003 July-August; 49(4): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851028
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A cytogenetic study of Kuwaiti couples with infertility and reproductive disorders: short arm deletion of chromosome 21 is associated with male infertility. Author(s): Alkhalaf M, Verghese L, Muharib N. Source: Annales De Genetique. 2002 July-September; 45(3): 147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381447
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A data mining approach to the development of a diagnostic test for male infertility. Author(s): Dzeroski S, Hristovski D, Kunej T, Peterlin B. Source: Stud Health Technol Inform. 2000; 77: 779-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11187659
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A large deletion of the repeat site in semenogelin I is not involved in male infertility. Author(s): Miyano S, Yoshida K, Yoshiike M, Miyamoto C, Furuichi Y, Iwamoto T. Source: International Journal of Molecular Medicine. 2003 April; 11(4): 435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632094
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A novel mutation (N233K) in the transactivating domain and the N756S mutation in the ligand binding domain of the androgen receptor gene are associated with male infertility. Author(s): Giwercman YL, Nikoshkov A, Bystrom B, Pousette A, Arver S, Wedell A. Source: Clinical Endocrinology. 2001 June; 54(6): 827-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422119
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Acta fifty years ago. Important study of male infertility. Author(s): Ulstein M. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1995 March; 74(3): 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7900520
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Adenosine triphosphate-binding cassette superfamily transporter gene expression in severe male infertility. Author(s): Larriba S, Bassas L, Egozcue S, Gimenez J, Ramos MD, Briceno O, Estivill X, Casals T. Source: Biology of Reproduction. 2001 August; 65(2): 394-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11466205
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Adult-onset idiopathic hypogonadotropic hypogonadism--a treatable form of male infertility. Author(s): Nachtigall LB, Boepple PA, Pralong FP, Crowley WF Jr. Source: The New England Journal of Medicine. 1997 February 6; 336(6): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010147
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Alexithymia in male infertility. Author(s): Conrad R, Schilling G, Langenbuch M, Haidl G, Liedtke R. Source: Human Reproduction (Oxford, England). 2001 March; 16(3): 587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228234
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Alterations in sperm protein phosphorylation in male infertility. Author(s): Hortas ML, Castilla JA, Gil MT, Samaniego F, Morell M, Redondo M. Source: Andrologia. 2001 September; 33(5): 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11683703
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An overview of male infertility in the era of intracytoplasmic sperm injection. Author(s): Kim ED. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2001 February; 64(2): 71-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11355331
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Analysis of fluorescence spectra from Chinese herbal medicine for male infertility. Author(s): Amano T, Kunimi K, Ohkawa M. Source: The American Journal of Chinese Medicine. 1995; 23(3-4): 213-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8571917
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Androgen insensitivity and male infertility. Author(s): Hiort O, Holterhus PM. Source: International Journal of Andrology. 2003 February; 26(1): 16-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534933
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Androgen receptor gene and male infertility. Author(s): Yong EL, Loy CJ, Sim KS. Source: Human Reproduction Update. 2003 January-February; 9(1): 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12638777
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Animal models of genetic causes of male infertility. Author(s): Christensen GL, Carrell DT. Source: Asian Journal of Andrology. 2002 September; 4(3): 213-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364979
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Aromatase inhibitors for male infertility. Author(s): Raman JD, Schlegel PN. Source: The Journal of Urology. 2002 February; 167(2 Pt 1): 624-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792932
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Assisted ejaculation combined with in vitro fertilisation: an effective technique treating male infertility due to spinal cord injury. Author(s): Hultling C, Levi R, Garoff L, Nylund L, Rosenborg L, Sjoblom P, Hillensjo T. Source: Paraplegia. 1994 July; 32(7): 463-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7970847
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Assisted reproductive techniques and male infertility. Author(s): Sigman M. Source: The Urologic Clinics of North America. 1994 August; 21(3): 505-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059504
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Association of oestrogen receptor alpha polymorphisms and androgen receptor CAG trinucleotide repeats with male infertility: a study in 109 Greek infertile men. Author(s): Kukuvitis A, Georgiou I, Bouba I, Tsirka A, Giannouli CH, Yapijakis C, Tarlatzis B, Bontis J, Lolis D, Sofikitis N, Papadimas J. Source: International Journal of Andrology. 2002 June; 25(3): 149-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031042
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AUA and ASRM produce recommendations for male infertility. American Urological Association, Inc and American Society for Reproductive Medicine. Author(s): Gangel EK; American Urological Association, Inc and American Society for Reproductive Medicine. Source: American Family Physician. 2002 June 15; 65(12): 2589-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12086246
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Bacterial infection and male infertility: absence of immunoglobulin A with specificity for common Escherichia coli 0-serotypes in seminal fluid of infertile men. Author(s): Fowler JE Jr, Mariano M. Source: The Journal of Urology. 1983 July; 130(1): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6191045
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Bacteriospermia and male infertility: a method for increasing the sensitivity of semen culture. Author(s): Villanueva-Diaz CA, Flores-Reyes GA, Beltran-Zuniga M, EchavarriaSanchez M, Ortiz-Ibarra FJ, Arredondo-Garcia JL. Source: Int J Fertil Womens Med. 1999 June-August; 44(4): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10499741
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Barrier contraceptive practice and male infertility as related factors to breast cancer in married women. Author(s): Gjorgov AN. Source: Medical Hypotheses. 1978 March-April; 4(2): 79-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=642850
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Barrier contraceptive practice and male infertility as related factors to breast cancer in married women. Preliminary results. Author(s): Gjorgov AN. Source: God Zb Med Fak Skopje. 1978; 24: 133-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=757157
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Barrier contraceptive practice and male infertility as related factors to breast cancer in married women. Preliminary results. Author(s): Gjorgov AN. Source: Oncology. 1978; 35(3): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=566883
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Barrier contraceptive practice and male infertility as related factors to female breast cancer. Author(s): Gjorgov AN. Source: God Zb Med Fak Skopje. 1978; 24: 101-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=757155
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Best practice policies for male infertility. Author(s): Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R. Source: Fertility and Sterility. 2002 May; 77(5): 873-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009338
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Best practice policies for male infertility. Author(s): Jarow JP, Sharlip ID, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R; Male Infertility Best Practice Policy Committee of the American Urological Association Inc. Source: The Journal of Urology. 2002 May; 167(5): 2138-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956464
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Beta-endorphin and male infertility. Author(s): Miralles-Garcia JM, Mories-Alvarez MT, Corrales-Hernandez JJ, Garcia-Diez CL. Source: Archives of Andrology. 1986; 16(3): 247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2946270
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Bilateral cryptorchidism: a cause of male infertility? A follow-up study of young males undergoing bilateral orchiorrhaphy during childhood. Author(s): Shahar E, Schachter A, Wolloch Y, Dintsman M. Source: Panminerva Medica. 1979 October-December; 21(4): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=45319
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Bilateral Leydig cell tumors and male infertility: case report. Author(s): Kondoh N, Koh E, Nakamura M, Namiki M, Kiyohara H, Okuyama A, Sonoda T. Source: Urologia Internationalis. 1991; 46(1): 104-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2024357
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Biological mechanisms of male infertility. Author(s): Ford WC. Source: Lancet. 2001 April 21; 357(9264): 1223-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11418145
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Blood serotonin levels and male infertility. Author(s): Gonzales GF, Garcia-Hjarles MA, Napuri R, Coyotupa J, Guerra-Garcia R. Source: Archives of Andrology. 1989; 22(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2712644
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Boxers and biopsies--separating fashion from fact in male infertility. Author(s): Turek PJ. Source: The Journal of Urology. 1998 October; 160(4): 1337. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751349
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Breaking down the barriers to reproduction in male infertility. Author(s): Davis N. Source: The Journal of Urology. 1998 May; 159(5): 1563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9554355
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Bromocriptine for male infertility. Author(s): Saidi K, Wenn RV, Sharif F. Source: Lancet. 1977 January 29; 1(8005): 250-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=64770
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Bromocriptine treatment for male infertility. Author(s): Madsen H, Andersen O, Hansen P. Source: Andrologia. 1980 July-August; 12(4): 379-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7425317
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CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. Author(s): Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, Singh L. Source: Journal of Andrology. 2002 November-December; 23(6): 815-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399527
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Cancer and male infertility. Author(s): Giwercman A, Petersen PM. Source: Bailliere's Best Practice & Research. Clinical Endocrinology & Metabolism. 2000 June; 14(3): 453-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097786
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Case-control study of leatherwork and male infertility. Author(s): Kurinczuk JJ, Clarke M. Source: Occupational and Environmental Medicine. 2001 April; 58(4): 217-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11245737
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Caution in use of interferon for male infertility. Author(s): Foresta C, Rossato M. Source: Lancet. 1994 October 8; 344(8928): 1027. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7934411
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CFTR gene mutations and male infertility. Author(s): Stuhrmann M, Dork T. Source: Andrologia. 2000 March; 32(2): 71-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755189
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Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Author(s): Ollero M, Gil-Guzman E, Lopez MC, Sharma RK, Agarwal A, Larson K, Evenson D, Thomas AJ Jr, Alvarez JG. Source: Human Reproduction (Oxford, England). 2001 September; 16(9): 1912-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527898
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Chlamydia trachomatis and male infertility in Tunisia. Author(s): Gdoura R, Keskes-Ammar L, Bouzid F, Eb F, Hammami A, Orfila J. Source: The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception. 2001 June; 6(2): 102-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518447
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Chromosomal alterations and male infertility. Author(s): Antonelli A, Gandini L, Petrinelli P, Marcucci L, Elli R, Lombardo F, Dondero F, Lenzi A. Source: J Endocrinol Invest. 2000 November; 23(10): 677-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11097433
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Clinical and laboratory management of male infertility: an opinion on its current status. Author(s): Oehninger S. Source: Journal of Andrology. 2000 November-December; 21(6): 814-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11105907
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Clinical approaches to male infertility with a case report of possible nifedipineinduced sperm dysfunction. Author(s): Enders G. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1997 March-April; 10(2): 131-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9071694
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Clinical aspects of male infertility. Author(s): Krausz C, Forti G. Source: Results Probl Cell Differ. 2000; 28: 1-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10626292
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Clinical review 64: Pathophysiology and natural history of male infertility. Author(s): Bhasin S, de Kretser DM, Baker HW. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 December; 79(6): 1525-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7989450
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Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection. Author(s): Meschede D, Lemcke B, Behre HM, De Geyter C, Nieschlag E, Horst J. Source: Human Reproduction (Oxford, England). 2000 July; 15(7): 1604-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10875874
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Glycodelins: role in regulation of reproduction, potential for contraceptive development and diagnosis of male infertility. Author(s): Seppala M, Koistinen H, Koistinen R, Mandelin E, Oehninger S, Clark GF, Dell A, Morris HR. Source: Human Reproduction (Oxford, England). 1998 June; 13 Suppl 3: 262-9L; Discussion 270. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755428
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HCG and HMG treatment of male infertility with pituitary problems. Author(s): Usui T, Ishibe T, Matsumoto S. Source: Urology. 1987 January; 29(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3099447
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Hemochromatosis and male infertility. Author(s): Oehninger S, Pike I, Slotnick N. Source: Obstetrics and Gynecology. 1998 October; 92(4 Pt 2): 652-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9764650
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High prevalence of male infertility in southeastern Nigeria. Author(s): Ikechebelu JI, Adinma JI, Orie EF, Ikegwuonu SO. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 November; 23(6): 657-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617473
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High-performance aircraft--a possible cause of male infertility. Author(s): Jequier AM. Source: British Journal of Urology. 1996 June; 77(6): 920-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8705237
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Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. Author(s): Bezold G, Lange M, Peter RU. Source: The New England Journal of Medicine. 2001 April 12; 344(15): 1172-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302150
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Hormonal disruptors and male infertility: are men at serious risk? Author(s): Lamb DJ. Source: Regulatory Toxicology and Pharmacology : Rtp. 1997 August; 26(1 Pt 1): 30-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9339475
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Hormonal exploration of male infertility. Author(s): Vermeulen A, Comhaire F, Vandeweghe M. Source: Acta Eur Fertil. 1979 September; 10(3): 105-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=121014
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How to determine the cause of male infertility. Author(s): Klotz PG. Source: Mod Med Asia. 1978 February; 14(2): 9-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=642913
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Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update. Author(s): Vogt PH. Source: Molecular Human Reproduction. 1998 August; 4(8): 739-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733430
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Human male infertility and Y chromosome deletions: role of the AZF-candidate genes DAZ, RBM and DFFRY. Author(s): Ferlin A, Moro E, Garolla A, Foresta C. Source: Human Reproduction (Oxford, England). 1999 July; 14(7): 1710-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10402373
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Human male infertility caused by degeneration and death of sperm in the epididymis. Author(s): Wilton LJ, Temple-Smith PD, Baker HW, de Kretser DM. Source: Fertility and Sterility. 1988 June; 49(6): 1052-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3371483
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Human male infertility may be due to a decrease of the protamine P2 content in sperm chromatin. Author(s): Belokopytova IA, Kostyleva EI, Tomilin AN, Vorob'ev VI. Source: Molecular Reproduction and Development. 1993 January; 34(1): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8418817
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Human male infertility, probably genetically determined, due to defective meiosis and spermatogenic arrest. Author(s): Chaganti RS, German J. Source: American Journal of Human Genetics. 1979 September; 31(5): 634-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=574357
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Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion. Author(s): Egozcue S, Blanco J, Vendrell JM, Garcia F, Veiga A, Aran B, Barri PN, Vidal F, Egozcue J. Source: Human Reproduction Update. 2000 January-February; 6(1): 93-105. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711834
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Human protamines and male infertility. Author(s): Khara KK, Vlad M, Griffiths M, Kennedy CR. Source: Journal of Assisted Reproduction and Genetics. 1997 May; 14(5): 282-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9147242
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Human seminal lectin. I. Demonstration and association with male infertility. Author(s): Mahadevan M, Trounson AO, Nayuda RV. Source: Fertility and Sterility. 1980 November; 34(5): 490-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7192222
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Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase lambda-deficient mice: possible implication for the pathogenesis of immotile cilia syndrome. Author(s): Kobayashi Y, Watanabe M, Okada Y, Sawa H, Takai H, Nakanishi M, Kawase Y, Suzuki H, Nagashima K, Ikeda K, Motoyama N. Source: Molecular and Cellular Biology. 2002 April; 22(8): 2769-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11909969
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Hyperprolactinaemia and male infertility. Author(s): Abbassy AA, Saikali WA. Source: British Journal of Urology. 1982 June; 54(3): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6809093
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Hyperprolactinaemia as a cause of male infertility in Ibadan. Author(s): Adejuwon CA, Ilesanmi AO, Ode EO. Source: West Afr J Med. 1999 January-March; 18(1): 17-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10876725
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Hyperprolactinemia and male infertility. Author(s): Wong TW, Jones TM. Source: Archives of Pathology & Laboratory Medicine. 1984 January; 108(1): 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6546335
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Iatrogen male infertility. Author(s): Mathe G. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1998; 52(5): 193-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755814
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Identification of human candidate genes for male infertility by digital differential display. Author(s): Olesen C, Hansen C, Bendsen E, Byskov AG, Schwinger E, Lopez-Pajares I, Jensen PK, Kristoffersson U, Schubert R, Van Assche E, Wahlstroem J, Lespinasse J, Tommerup N. Source: Molecular Human Reproduction. 2001 January; 7(1): 11-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11134355
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Immunohistochemical localization of calmodulin in the testes of patients with idiopathic male infertility. Author(s): Tsuji Y, Sano M, Nagahama M, Tsutsui Y, Yamamoto M, Miyake K. Source: International Journal of Andrology. 1993 June; 16(3): 215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8359937
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Improvement of sexual activity, pregnancy rate, and low plasma testosterone after bilateral varicocelectomy in impotence and male infertility patients. Author(s): Younes AK. Source: Archives of Andrology. 2003 May-June; 49(3): 219-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746101
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In vitro fertilization for male infertility: when and how? Author(s): Hall J, Fishel S. Source: Baillieres Clin Obstet Gynaecol. 1997 December; 11(4): 711-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9692012
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Increased sperm mitochondrial DNA content in male infertility. Author(s): May-Panloup P, Chretien MF, Savagner F, Vasseur C, Jean M, Malthiery Y, Reynier P. Source: Human Reproduction (Oxford, England). 2003 March; 18(3): 550-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615823
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Individualized homeopathic therapy for male infertility. Author(s): Gerhar I, Wallis E. Source: Homeopathy. 2002 July; 91(3): 133-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12322866
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Infection and pyospermia in male infertility. Author(s): Bar-Chama N, Fisch H. Source: World Journal of Urology. 1993; 11(2): 76-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8343798
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Infection and pyospermia in male infertility. Is it really a problem? Author(s): Bar-Chama N, Goluboff E, Fisch H. Source: The Urologic Clinics of North America. 1994 August; 21(3): 469-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059501
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Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Author(s): Purvis K, Christiansen E. Source: International Journal of Andrology. 1993 February; 16(1): 1-13. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8468091
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Influence of acupuncture on idiopathic male infertility in assisted reproductive technology. Author(s): Zhang M, Huang G, Lu F, Paulus WE, Sterzik K. Source: J Huazhong Univ Sci Technolog Med Sci. 2002; 22(3): 228-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658811
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Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Author(s): Maeda Y, Shiratsuchi A, Namiki M, Nakanishi Y. Source: Cell Death and Differentiation. 2002 July; 9(7): 742-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058279
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Insights into the molecular basis of male infertility. Author(s): Rocha D, Affara NA. Source: Indian J Physiol Pharmacol. 2001 April; 45(2): 136-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11480220
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Intracytoplasmic sperm injection into oocytes of severe male infertility patients: UAMS experience. University of Arkansas for Medical Sciences. Author(s): Mahadevan MM, Miller MM, Maris MO, Moutos D, Finkbeiner A. Source: J Ark Med Soc. 1998 April; 94(11): 487-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9575718
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Is 24-h sperm motility a useful IVF measure when male infertility is not apparent? Author(s): Eskandar M. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 April; 81(4): 328-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952463
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Is antioxidant therapy a promising strategy to improve human reproduction? Are anti-oxidants useful in the treatment of male infertility? Author(s): Martin-Du Pan RC, Sakkas D. Source: Human Reproduction (Oxford, England). 1998 November; 13(11): 2984-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853840
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Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. Author(s): Schlegel PN. Source: Urology. 1997 January; 49(1): 83-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9000191
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Is seminal prostatic acid phosphatase a reliable marker for male infertility? Author(s): Singh G, Adaikan PG, Ng YK. Source: Singapore Med J. 1996 December; 37(6): 598-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9104058
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Isoprenoid pathway dysfunction in human male infertility. Author(s): Kurup RK, Kurup PA. Source: Archives of Andrology. 2003 March-April; 49(2): 117-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623748
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It's a knockout! Male infertility and neuropathology. Author(s): Anagnostopoulos AV. Source: Trends in Genetics : Tig. 2002 January; 18(1): 8-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750688
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Kallikrein treatment of male infertility. Author(s): Sato H, Mochimaru F, Kobayashi T, Iizuka R, Kaneko S, Moriwaki C. Source: Advances in Experimental Medicine and Biology. 1979; 120A: 529-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=495333
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Klinefelter's syndrome in the male infertility clinic. Author(s): Jarow JP. Source: The Journal of Urology. 2000 February; 163(2): 667. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10647705
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Klinefelter's syndrome in the male infertility clinic. Author(s): Okada H, Fujioka H, Tatsumi N, Kanzaki M, Okuda Y, Fujisawa M, Hazama M, Matsumoto O, Gohji K, Arakawa S, Kamidono S. Source: Human Reproduction (Oxford, England). 1999 April; 14(4): 946-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221225
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Laboratory diagnosis of male infertility. Author(s): Urry RL. Source: Clin Lab Med. 1985 June; 5(2): 355-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4028659
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Laboratory testing in the evaluation of male infertility. A rational approach. Author(s): Sigman M. Source: World Journal of Urology. 1993; 11(2): 96-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8343801
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Lack of association between polymorphisms in the testis-specific angiotensin converting enzyme gene and male infertility in an Asian population. Author(s): Liao WX, Roy AC. Source: Molecular Human Reproduction. 2002 March; 8(3): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870238
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Lack of association between Y chromosome haplogroups and male infertility in Japanese men. Author(s): Carvalho CM, Fujisawa M, Shirakawa T, Gotoh A, Kamidono S, Freitas Paulo T, Santos SE, Rocha J, Pena SD, Santos FR. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 152-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494434
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Lactic dehydrogenase-C4 activity in seminal plasma and male infertility. Author(s): Noguera Velasco JA, Tovar Zapata I, Martinez Hernandez P, Perez Albacete M, Tortosa Oltra J, Parrilla Paricio JJ. Source: Fertility and Sterility. 1993 August; 60(2): 331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8339833
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L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Author(s): Costa M, Canale D, Filicori M, D'lddio S, Lenzi A. Source: Andrologia. 1994 May-June; 26(3): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8085668
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Learning to knock out male infertility. Author(s): May M. Source: Environmental Health Perspectives. 1998 March; 106(3): A132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514981
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Leukocytospermia in male infertility patients in China. Author(s): Wang AW, Politch J, Anderson D. Source: Andrologia. 1994 May-June; 26(3): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7521990
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Levamisole treatment in male infertility due to spermagglutinins. Author(s): Luisi M, Gasperi M, Franchi F, D'Acunto A, Tauro CS. Source: Lancet. 1982 July 3; 2(8288): 47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6123779
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Leydig cell tumour of the testis: a rare cause of male infertility. Author(s): Mostafid H, Nawrocki J, Fletcher MS, Vaughan NJ, Melcher DH. Source: British Journal of Urology. 1998 April; 81(4): 651. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9598654
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Lifestyle and environmental contribution to male infertility. Author(s): Sharpe RM. Source: British Medical Bulletin. 2000; 56(3): 630-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11255550
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Life-threatening conditions associated with male infertility. Author(s): Jarow JP. Source: The Urologic Clinics of North America. 1994 August; 21(3): 409-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059497
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Ligation of the left spermatic vein in the treatment of male infertility. Author(s): Lukkarinen O, Hellstrom P, Ronnberg L. Source: Ann Chir Gynaecol. 1984; 73(6): 342-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6529138
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Limitation of gamete intrafallopian transfer in the treatment of male infertility. Author(s): Yovich JL, Matson PL, Turner SR, Richardson P, Yovich JM. Source: The Medical Journal of Australia. 1986 April 14; 144(8): 444. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3959977
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Linkage between male infertility and trinucleotide repeat expansion in the androgenreceptor gene. Author(s): Dowsing AT, Yong EL, Clark M, McLachlan RI, de Kretser DM, Trounson AO. Source: Lancet. 1999 August 21; 354(9179): 640-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466666
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Lipid peroxidation and antioxidant enzymes in male infertility. Author(s): Dandekar SP, Nadkarni GD, Kulkarni VS, Punekar S. Source: Journal of Postgraduate Medicine. 2002 July-September; 48(3): 186-89; Discussion 189-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12432192
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Long polyglutamine tracts in the androgen receptor are associated with reduced transactivation, impaired sperm production, and male infertility. Author(s): Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 November; 82(11): 3777-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360540
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Low chiasma frequency as an aetiological factor in male infertility. Author(s): Micic M, Micic S, Diklic V. Source: Clinical Genetics. 1982 November; 22(5): 266-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7151310
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Low plasma testosterone in varicocele patients with impotence and male infertility. Author(s): Younes AK. Source: Archives of Andrology. 2000 November-December; 45(3): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11111867
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Lycopene therapy in idiopathic male infertility--a preliminary report. Author(s): Gupta NP, Kumar R. Source: International Urology and Nephrology. 2002; 34(3): 369-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899230
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Male infertility caused by epididymal dysfunction in transgenic mice expressing a dominant negative mutation of retinoic acid receptor alpha 1. Author(s): Costa SL, Boekelheide K, Vanderhyden BC, Seth R, McBurney MW. Source: Biology of Reproduction. 1997 April; 56(4): 985-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9096882
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Male infertility of undetermined etiology. Author(s): Baker HW. Source: Curr Ther Endocrinol Metab. 1997; 6: 359-63. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9174771
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Male infertility. Author(s): de Kretser DM. Source: Lancet. 1997 March 15; 349(9054): 787-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9074589
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Male infertility. Author(s): Iammarrone E, Balet R, Lower AM, Gillott C, Grudzinskas JG. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2003 April; 17(2): 211-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12758096
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Male infertility. Author(s): Wiesenfeld HC. Source: The New England Journal of Medicine. 1995 June 29; 332(26): 1790; Author Reply 1791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7760905
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Male infertility. Author(s): Tur-Kaspa I, Maor Y, Dor J. Source: The New England Journal of Medicine. 1995 June 29; 332(26): 1790; Author Reply 1791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7760904
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Male infertility. Author(s): Amelar RD, Dubin L, Schoenfeld C. Source: The New England Journal of Medicine. 1995 June 29; 332(26): 1790; Author Reply 1791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7539112
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Male infertility: diagnosis and treatment. Author(s): Ross LS, Niederberger CS. Source: Compr Ther. 1995 June; 21(6): 276-82. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7664538
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Measuring male infertility: epidemiological aspects. Author(s): Pasqualotto FF, Locambo CV, Athayde KS, Arap S. Source: Revista Do Hospital Das Clinicas. 2003 May-June; 58(3): 173-8. Epub 2003 July 22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894315
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Mitochondrial mutations and male infertility. Author(s): St John JC, Cooke ID, Barratt CL. Source: Nature Medicine. 1997 February; 3(2): 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018221
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MR imaging in male infertility. Author(s): Parsons RB, Fisher AM, Bar-Chama N, Mitty HA. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. 1997 May-June; 17(3): 627-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9153701
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MR imaging of male infertility with an endorectal surface coil. Author(s): Kim MJ, Lee JT, Lee MS, Suh JS, Yoo HS. Source: Abdominal Imaging. 1997 May-June; 22(3): 348-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9107667
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New insights into the etiology and treatment of male infertility. Author(s): Goldstein M. Source: The Journal of Urology. 1997 November; 158(5): 1808-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9334607
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New technique treats male infertility. Author(s): Fitzpatrick M. Source: Jama : the Journal of the American Medical Association. 1999 October 20; 282(15): 1414. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10535420
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No evidence for uniparental disomy of the sex chromosomes in idiopathic male infertility. Author(s): Meschede D, Dworniczak B, Behre HM, Nieschlag E, Horst J. Source: Molecular Human Reproduction. 2000 January; 6(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10611253
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On the origin and frequency of Y chromosome deletions responsible for severe male infertility. Author(s): Edwards RG, Bishop CE. Source: Molecular Human Reproduction. 1997 July; 3(7): 549-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9268131
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Oral antioxidants and male infertility. Author(s): Mahmoud AM, Comhaire FH, Christophe AB. Source: Human Reproduction (Oxford, England). 1999 December; 14(12): 3149-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10601111
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Overexpression of the matrix metalloproteinase matrilysin results in premature mammary gland differentiation and male infertility. Author(s): Rudolph-Owen LA, Cannon P, Matrisian LM. Source: Molecular Biology of the Cell. 1998 February; 9(2): 421-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9450965
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Oxidative stress and male infertility. Author(s): Sanocka D, Miesel R, Jedrzejczak P, Kurpisz MK. Source: Journal of Andrology. 1996 July-August; 17(4): 449-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8889709
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Pathogenesis and management of male infertility. Author(s): Skakkebaek NE, Giwercman A, de Kretser D. Source: Lancet. 1994 June 11; 343(8911): 1473-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7911182
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Pathophysiology of varicoceles in male infertility. Author(s): Naughton CK, Nangia AK, Agarwal A. Source: Human Reproduction Update. 2001 September-October; 7(5): 473-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11556494
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Perceptions of and attitudes towards male infertility in northern Botswana: some implications for family planning and AIDS prevention policies. Author(s): Upton RL. Source: Afr J Reprod Health. 2002 December; 6(3): 103-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685415
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Place of intracytoplasmic sperm injection in management of male infertility. Author(s): Oehninger S. Source: Lancet. 2001 June 30; 357(9274): 2068-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11445092
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Polymorphisms of glutathione S-transferase M1 and male infertility in Taiwanese patients with varicocele. Author(s): Chen SS, Chang LS, Chen HW, Wei YH. Source: Human Reproduction (Oxford, England). 2002 March; 17(3): 718-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870126
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Potential association between male infertility and occupational psychological stress. Author(s): Sheiner EK, Sheiner E, Carel R, Potashnik G, Shoham-Vardi I. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2002 December; 44(12): 1093-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12500450
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Proceedings of the 7th Andrology Symposium. Treatment of male infertility-viewpoints, controversies, perspectives. Giessen, Germany, 17 November 2001. Author(s): Schill WB, Schuppe HC, Weid W, Manning M. Source: Andrologia. 2002 October; 34(5): 325-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390091
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Pronuclear morphology scoring and chromosomal status of embryos in severe male infertility. Author(s): Kahraman S, Kumtepe Y, Sertyel S, Donmez E, Benkhalifa M, Findikli N, Vanderzwalmen P. Source: Human Reproduction (Oxford, England). 2002 December; 17(12): 3193-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456623
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Prostatitis and male infertility: evidence and links. Author(s): Schoor RA. Source: Curr Urol Rep. 2002 August; 3(4): 324-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149165
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Quantitative infra-red thermography to identify varicoceles as the cause of male infertility. Author(s): Gallo LM, Bosiger P, Rageth CJ, Stucki D. Source: Biomed Tech (Berl). 1985 November; 30(11): 284-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4074813
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Questionnaire survey of male infertility in cystic fibrosis. Author(s): Rodgers HC, Baldwin DR, Knox AJ. Source: Respiratory Medicine. 2000 October; 94(10): 1002-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11059956
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Randomized trial of partial zona dissection for male infertility. Author(s): Tummon IS, Gore-Langton RE, Daniel SA, Squires PM, Koval JJ, Alsalili MB, Martin JS, Kaplan BR, Nisker JA, Yuzpe AA. Source: Fertility and Sterility. 1995 April; 63(4): 842-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7890072
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Re: Aromatase inhibitors for male infertility. Author(s): Terris MK, McCallum SW. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1509. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352445
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Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Author(s): Wallerand H, Remy-Martin A, Chabannes E, Bermont L, Adessi GL, Bittard H. Source: Fertility and Sterility. 2001 October; 76(4): 769-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591412
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Relationships between personality traits, seminal parameters and hormones in male infertility. Author(s): Conrad R, Schilling G, Haidl G, Geiser F, Imbierowicz K, Liedtke R. Source: Andrologia. 2002 October; 34(5): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390090
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Reproductive technologies for male infertility. Author(s): Khorram O, Patrizio P, Wang C, Swerdloff R. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 June; 86(6): 2373-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11397826
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Research of single mitochondrial nucleotide substitutions in male infertility should consider human mitochondrial haplogroups. Author(s): Montiel-Sosa JF, Enriquez JA, Lopez-Perez MJ. Source: International Journal of Andrology. 2002 December; 25(6): 372-3; Author Reply 374. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12406370
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RNA-binding proteins and human male infertility. Author(s): Cooke HJ, Elliott DJ. Source: Trends in Genetics : Tig. 1997 March; 13(3): 87-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9066264
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Role of endocrine factors in male infertility. Author(s): Csenke Z, Torok L, Szollosi J, Scultety S. Source: International Urology and Nephrology. 1995; 27(2): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7591580
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Role of oxidants in male infertility: rationale, significance, and treatment. Author(s): Agarwal A, Saleh RA. Source: The Urologic Clinics of North America. 2002 November; 29(4): 817-27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516754
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Role of reactive oxygen species in male infertility. Author(s): Sharma RK, Agarwal A. Source: Urology. 1996 December; 48(6): 835-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8973665
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Screening for microdeletions in human Y chromosome--AZF candidate genes and male infertility. Author(s): Raicu F, Popa L, Apostol P, Cimponeriu D, Dan L, Ilinca E, Dracea LL, Marinescu B, Gavrila L. Source: Journal of Cellular and Molecular Medicine. 2003 January-March; 7(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767260
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Searching for candidate genes for male infertility. Author(s): Truong BN, Moses EK, Armes JE, Venter DJ, Baker HW. Source: Asian Journal of Andrology. 2003 June; 5(2): 137-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12778326
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Seminal tract washout: a new diagnostic tool in complicated cases of male infertility. Author(s): Colpi GM, Negri L, Scroppo FI, Grugnetti C, Patrizio P. Source: Journal of Andrology. 1994 November-December; 15 Suppl: 17S-22S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7721670
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Should male infertility patients be tested for leukocytospermia? Author(s): Anderson DJ. Source: Fertility and Sterility. 1995 February; 63(2): 246-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7843424
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Significant medical pathology uncovered by a comprehensive male infertility evaluation. Author(s): Honig SC, Lipshultz LI, Jarow J. Source: Fertility and Sterility. 1994 November; 62(5): 1028-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7926114
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Sperm morphology analysis (strict criteria) in male infertility is not a prognostic factor in intrauterine insemination with husband's sperm. Author(s): Matorras R, Corcostegui B, Perez C, Mandiola M, Mendoza R, RodriguezEscudero FJ. Source: Fertility and Sterility. 1995 March; 63(3): 608-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7851595
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Spinal cord injury and male infertility. Author(s): Monga M, Gordon Z, Rajasekaran M. Source: Zhonghua Nan Ke Xue. 2002; 8(4): 235-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491681
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Spontaneous pregnancy in couples waiting for artificial insemination donor because of severe male infertility. Author(s): Matorras R, Diez J, Corcostegui B, Gutierrez de Teran G, Garcia JM, Pijoan JI, Rodriguez-Escudero FJ. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1996 December 27; 70(2): 175-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9119099
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Stress, sexual dysfunctions, and male infertility. Author(s): Lenzi A, Lombardo F, Salacone P, Gandini L, Jannini EA. Source: J Endocrinol Invest. 2003; 26(3 Suppl): 72-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834026
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Successful use of interferon for male infertility. Author(s): Yamamoto M, Miyake K. Source: Lancet. 1994 August 27; 344(8922): 614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7802779
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The effective cumulative pregnancy rate of different modes of treatment of male infertility. Author(s): Comhaire F, Milingos S, Liapi A, Gordts S, Campo R, Depypere H, Dhont M, Schoonjans F. Source: Andrologia. 1995 July-August; 27(4): 217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7486032
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The potential of intracytoplasmic sperm injection (ICSI) to transmit genetic defects causing male infertility. Author(s): de Kretser DM. Source: Reproduction, Fertility, and Development. 1995; 7(2): 137-41; Discussion 141-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480831
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The use of assisted reproduction technology (ART) for achieving conception in male infertility. Author(s): Fishel SB, Thornton S. Source: British Journal of Urology. 1995 June; 75 Suppl 1: 50-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7613857
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The use of intracytoplasmic sperm injection for the treatment of severe and extreme male infertility. Author(s): Bourne H, Richings N, Harari O, Watkins W, Speirs AL, Johnston WI, Baker HW. Source: Reproduction, Fertility, and Development. 1995; 7(2): 237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480842
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Transrectal ultrasound in male infertility. Author(s): Li MK, Tan HH. Source: Ann Acad Med Singapore. 1995 July; 24(4): 566-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8849190
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Treatment of male infertility. Author(s): Howards SS. Source: The New England Journal of Medicine. 1995 February 2; 332(5): 312-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7816068
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Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1). Human bladder washings and transitional cell carcinoma of the bladder; and (2). Human sperm and male infertility. Author(s): McKelvey-Martin VJ, Melia N, Walsh IK, Johnston SR, Hughes CM, Lewis SE, Thompson W. Source: Mutation Research. 1997 April 29; 375(2): 93-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9202720
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Understanding new genetics of male infertility. Author(s): Maduro MR, Lamb DJ. Source: The Journal of Urology. 2002 November; 168(5): 2197-205. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394759
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Unilateral obstruction of the vas deferens caused by childhood inguinal herniorrhaphy in male infertility patients. Author(s): Matsuda T, Horii Y, Yoshida O. Source: Fertility and Sterility. 1992 September; 58(3): 609-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1521659
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Unwarranted demand for body parts of endangered animal species for treatment of male infertility. Author(s): Ng SC, Ganesan A. Source: Asian Journal of Andrology. 2000 June; 2(2): 158. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232797
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Ureaplasma urealyticum (T. mycoplasma) and male infertility in topical countries. Author(s): Ladipo OA, Osoba AO. Source: Afr J Med Med Sci. 1978 December; 7(4): 187-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=108940
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Ureaplasma urealyticum (T-mycoplasma) infection: does it have a role in male infertility? Author(s): Desai S, Cohen S, Khatamee M, Leiter E. Source: The Journal of Urology. 1980 October; 124(4): 469-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7420587
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Urinary vasopressin in male infertility. Author(s): Puri S, Puri VN. Source: Archives of Andrology. 1985; 14(2-3): 263-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4062420
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Urogenital inflammations: aetiology, diagnosis and their correlation with varicocele and male infertility. Author(s): Gattuccio F, Di Trapani D, Romano C, Turtulici B, Milici M, Pavone C, D'Alia O, Alaimo R, Latteri MA. Source: Acta Eur Fertil. 1988 July-August; 19(4): 201-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3067482
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Use of immature germ cells for the treatment of male infertility. Author(s): Tesarik J. Source: Baillieres Clin Obstet Gynaecol. 1997 December; 11(4): 763-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9692016
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Use of imported cryopreserved hamster oocytes in the diagnosis of male infertility. Author(s): Quinn P, Whittingham DG, Matthews CD, Seamark RF, Cox LW. Source: Clin Reprod Fertil. 1983 December; 2(4): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6678605
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Use of testicular sperm for the treatment of male infertility. Author(s): Tournaye H. Source: Baillieres Clin Obstet Gynaecol. 1997 December; 11(4): 753-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9692015
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Varicocele and its role in male infertility. Author(s): Comhaire FH. Source: Oxf Rev Reprod Biol. 1986; 8: 165-213. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3540802
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Varicocele and male infertility. Author(s): Reidy JF. Source: Br J Hosp Med. 1987 November; 38(5): 484. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3690083
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Varicocele and male infertility: part I. Preface. Author(s): Benoff S, Gilbert BR. Source: Human Reproduction Update. 2001 January-February; 7(1): 47-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11212074
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Varicocele as a contributing factor to male infertility. A preliminary report. Author(s): Davis JE, Clyman MJ, Decker A, Ober WB, Roland M. Source: Int J Fertil. 1965 October-December; 10(4): 359-72. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5842645
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Varicocelectomy as therapy in male infertility: a study of 504 cases. Author(s): Dubin L, Amelar RD. Source: The Journal of Urology. 1975 May; 113(5): 640-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1127806
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Varicocelectomy as therapy in male infertility: a study of 504 cases. Author(s): Dubin L, Amelar RD. Source: Fertility and Sterility. 1975 March; 26(3): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1116617
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Varicocelectomy in the management of male infertility. Author(s): Rajan R, Valayil C, Thomas M, Jayakumar B. Source: J Obstet Gynaecol India. 1978 October; 28(5): 833-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=750244
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Varicoceles and male infertility. Author(s): Boyd AS. Source: American Family Physician. 1988 February; 37(2): 252-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3278567
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Vascular lesions in testes associated with male infertility in Cameroon. Possible relationship to parasitic disease. Author(s): Nasah BT, Cox JN. Source: Virchows Arch a Pathol Anat Histol. 1978 March 10; 377(3): 225-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=148151
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Warning note on male infertility treatment. Author(s): Foresta C, Ferlin A, Galeazzi C, Rossato M. Source: Lancet. 1996 March 2; 347(9001): 618. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8596343
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What forms of male infertility are there left to cure? Author(s): Silber SJ. Source: Human Reproduction (Oxford, England). 1995 March; 10(3): 503-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7782421
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Wheat germ agglutinin (WGA) receptors on human sperm membrane and male infertility. Author(s): Fei WY, Hao XW. Source: Archives of Andrology. 1990; 24(1): 97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2327818
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Which efforts towards conservative treatment of male infertility will be successful? Antibiotic therapy. Author(s): Weidner W. Source: Andrologia. 1999 September; 31(5): 297. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526640
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Which efforts towards conservative treatment of male infertility will be successful? Antiphlogistics and glucocorticoids. Author(s): Krause W. Source: Andrologia. 1999 September; 31(5): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526642
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Which efforts towards conservative treatment of male infertility will be successful? Mast cell blockers. Author(s): Haidl G. Source: Andrologia. 1999 September; 31(5): 299-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526641
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Which efforts towards conservative treatment of male infertility will be successful? Reactive oxygen species, antioxidants, and sperm phospholipids. Author(s): Comhaire F, Zalata A, Christophe A, Mahmoud A, Depuydt C, Dhooge W. Source: Andrologia. 1999 September; 31(5): 295-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526639
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Whither the investigation of male infertility? Is FSH measurement redundant and should all azoospermic patients have testicular biopsy? Author(s): Wu FC. Source: Human Reproduction (Oxford, England). 1995 August; 10(8): 1945-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8567818
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Withered Yang: a review of traditional Chinese medical treatment of male infertility and erectile dysfunction. Author(s): Crimmel AS, Conner CS, Monga M. Source: Journal of Andrology. 2001 March-April; 22(2): 173-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11229790
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Workup for male infertility. Author(s): Grunfeld L. Source: J Reprod Med. 1989 February; 34(2): 143-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2647974
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Xenobiotic metabolism, genetic polymorphisms and male infertility. Author(s): Schuppe HC, Wieneke P, Donat S, Fritsche E, Kohn FM, Abel J. Source: Andrologia. 2000 September; 32(4-5): 255-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11021517
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Xenoesterogens and male infertility: myth or reality? Author(s): Rozati R, Reddy PP, Reddanna P, Mujtaba R. Source: Asian Journal of Andrology. 2000 December; 2(4): 263-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11202414
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Y chromosome and male infertility. Author(s): Cooke HJ. Source: Reviews of Reproduction. 1999 January; 4(1): 5-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051097
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Y chromosome and male infertility. Author(s): Krausz C, McElreavey K. Source: Frontiers in Bioscience : a Journal and Virtual Library. 1999 January 15; 4: E1-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9889182
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Y chromosome genes and male infertility. Author(s): Pagani R, Brugh VM 3rd, Lamb DJ. Source: The Urologic Clinics of North America. 2002 November; 29(4): 745-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516749
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Y-chromosome deletions and male infertility: state of the art and clinical implications. Author(s): Roberts KP. Source: Journal of Andrology. 1998 May-June; 19(3): 255-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9639042
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Y-chromosome microdeletions and male infertility. Author(s): Bhasin S, Ma K, de Kretser DM. Source: Annals of Medicine. 1997 August; 29(4): 261-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9375979
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Zinc deficiency and male infertility. Author(s): Dincer SL, Oz SG. Source: Hosp Pract (Off Ed). 1990 May 30; 25(5A): 20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2111822
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Zona drilling: a new approach to male infertility. Author(s): Gordon JW. Source: J in Vitro Fert Embryo Transf. 1990 October; 7(5): 223-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2254682
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CHAPTER 2. NUTRITION AND MALE INFERTILITY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and male infertility.
Finding Nutrition Studies on Male Infertility 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 “male infertility” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “male infertility” (or a synonym): •
Antibody-mediated causes of male infertility. Source: Haas, G G Urol-Clin-North-Am. 1987 August; 14(3): 539-50 0094-0143
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Male infertility and environmental exposure to lead and cadmium. Author(s): Department of Obstetrics and Gynecology, North Shore University HospitalNew York University School of Medicine, Manhasset 11032, USA.
[email protected] Source: Benoff, S Jacob, A Hurley, I R Hum-Reprod-Update. 2000 Mar-April; 6(2): 107-21 1355-4786
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Male infertility: nutritional and environmental considerations. Author(s): Green Valley Health, Hagerstown, MD 21742, USA. Source: Sinclair, S Altern-Med-Revolume 2000 February; 5(1): 28-38 1089-5159
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Medical treatment of male infertility. Source: Hirsch, I H Lipshultz, L I Urol-Clin-North-Am. 1987 May; 14(2): 307-22 00940143
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Superoxide dismutase activities of spermatozoa and seminal plasma are not correlated with male infertility. Author(s): Department of Obstetrics and Gynecology, China Medical College Hospital, Taichung, Taiwan. Source: Hsieh, Y Y Sun, Y L Chang, C C Lee, Y S Tsai, H D Lin, C S J-Clin-Lab-Anal. 2002; 16(3): 127-31 0887-8013
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The therapeutic effects of Sheng Jing Zhong Zi Tang in treating male infertility. Author(s): First Clinical College Affiliated to Xi'an University of Medical Sciences, Shannxi Province 710061. Source: Yang, B Zhang, C Du, L Xue, W Zou, P J-Tradit-Chin-Med. 2001 June; 21(2): 96-9 0254-6272
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Therapeutic effect of gonadotropins with and without a GnRH analogue (D6tryptophan) in male infertility due to idiopathic oligoasthenospermia. Author(s): Department of Endocrinological Gynecology, University of Palermo, Italy. Source: Luciano, A Fascella, A Lo Meo, C Palisi, F Dones, F Tiberio, C Acta-Eur-Fertil. 1992 Sep-October; 23(5): 225-31 0587-2421
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
The following is a specific Web list relating to male infertility; 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 Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html
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Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com •
Minerals Acetyl-l-carnitine Source: Healthnotes, Inc.; www.healthnotes.com Carnitine (l-carnitine) Source: Integrative Medicine Communications; www.drkoop.com L-carnitine Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com
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Food and Diet Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com Weight Loss and Obesity Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. CLINICAL TRIALS AND MALE INFERTILITY Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning male infertility.
Recent Trials on Male Infertility The following is a list of recent trials dedicated to male infertility.8 Further information on a trial is available at the Web site indicated. •
Effect of environmental exposures on the egg fertilizing ability of human sperm Condition(s): Male Infertility; Testicular Diseases; Urologic and Male Genital Diseases; Lead Poisoning Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: Our data indicate that environmental exposure to the heavy metal lead are more widespread than currently appreciated and that such exposures are associated with the production of human male subfertility. Lead's effects are observed in male partners of infertile couples attending an IVF clinical, in men acting as semen donors in an artificial insemination program and in men representative of the general public. Our goal is to identify the mechanism(s) underlying lead's anti-fertility action. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012480
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Role of the toxic metal cadmium in the mechanism producing infertility with a varicocele Condition(s): Varicocele; Male Infertility; Hypospermatogenesis; Non-obstructive azoospermia
8
These are listed at www.ClinicalTrials.gov.
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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: Varicose veins in the scrotum (varicocele) are responsible for >20% of male infertility in the US. Varicocele are associated with decreased sperm number and markedly reduced sperm fertilizing ability. Surgical repair or removal of varicocele restores fertility in only 1/3 of cases. The goal of this study is to identify markers that predict the outcome of variocele correction. This would offer considerable health cost savings. Based on preliminary findings, we will obtain testis biopsies and semen specimens from infertile men with varicocele and prospectively examining the levels of cadmium, a toxic metal, and expression of genes required for normal sperm function. The semen and biopsies will be obtained during clinically dictated procedures. Cadmium and gene expression will be compared with response to varicocele repair (i.e., increased sperm production; pregnancy). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00044369
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 “male infertility” (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 4. PATENTS ON MALE INFERTILITY 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 “male infertility” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on male infertility, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Male Infertility By performing a patent search focusing on male infertility, 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 male infertility: •
DNA probe for male infertility Inventor(s): Humphreys-Beher; Michael G. (Gainesville, FL) Assignee(s): University of Florida (gainesville, Fl) Patent Number: 5,176,997 Date filed: February 22, 1991 Abstract: The subject invention pertains to a novel means of identifying male infertility. The novel method involves the identification of a unique restriction enzyme digestion pattern which is highly specific to individuals with male sperm binding infertility. Excerpt(s): Infertility is a problem that plagues many couples. There are a great number of reasons why difficulty in achieving conception may be encountered, and, because of the complexity of the issues involved, this problem is still very prevalent. In recent years, our knowledge and understanding of the biology and chemistry of fertilization has expanded rapidly. Much of what we know is drawn from in vitro experiments with mouse gametes. It is believed that the strategem described for fertilization of mouse gametes applies to in vivo fertilization of most mammals, including humans. It is well established that one of the major factors in reproductive failure can be the inability of the sperm to properly associate with, and penetrate, the egg. This type of infertility can be identified by the in vitro sperm binding/penetration assay utilizing the zona pellucida-free hamster egg. While the sperm of some individuals demonstrates a complete inability to penetrate the hamster egg, often there is also an accompanying significant reduction in sperm binding capacity (Kretzer, P., E. Pope, J. B. Younger, R. E. Blackwell [1987] "Long term follow-up of patients with zero hamster tests," The American Fertility Society [Abstract]). The path leading to fertilization consists of several steps that occur in a precise order. Fertilization begins when sperm associates with ovulated eggs at the cell surfaces. The egg is surrounded by a thick extracellular matrix known as the zona pellucida. Attachment of sperm to the egg appears to be mediated in part by a specific zona pellucida glycoprotein ZP3 (Bleil, J. D., and P. M. Wasserman [1984] Dev. Biol. 104:243-347). The functional group of the glycoprotein is the oligosaccharide moiety of the molecule (Florman, H. M., K. B. Bechtl, and P. M. Wasserman [1984] Dev. Biol. 104:243-247; Shur, B. D. and G. Hall [1982] J. Cell Biol. 95:574). Both sperm adhesion and penetration following attachment are mediated by sperm associated proteins. Web site: http://www.delphion.com/details?pn=US05176997__
•
Immortalized and malignant human prostatic cell lines Inventor(s): Rhim; Johng S. (Potomac, MD), Webber; Mukta M. (Eagle, MI) Assignee(s): Board of Trustees Operating Michigan State University (east Lansing, Mi), The United States of America AS Represented by the Deparmtent of Health (washington, Dc) Patent Number: 5,824,488 Date filed: April 28, 1994
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Abstract: Immortalized malignant human prostatic epithelial and fibroblast cell lines are described containing DNA of a human papillomavirus (HPV) and similar cell lines containing DNA of a human papillomavirus and an activated viral ras oncogene, such as v-Ki-ras. The cell lines are useful for research on drugs for treatment of prostatic cancer and other diseases. The cell lines are useful for research on causes, treatment and prevention of prostate cancer, benign prostatic hyperplasia, male infertility, birth defects, aging and assessment of environmental toxic agents. Excerpt(s): The present invention relates to human prostatic epithelial and fibroblast cell lines which have been immortalized. In particular, the present invention relates to nonmalignant cell lines immortalized with DNA of human papillomavirus (HPV) and malignant cell lines containing DNA of HPV and ras oncogene. Human cells are generally difficult to grow and maintain in long-term cultures in vitro. They have a limited life span in culture, grow for a short time and usually after 4 or 5 sub-cultures, they undergo senescence and die. Prostate cancer is the leading cancer in men in the United States, in terms of incidence. Thirty-two percent (32%) of all cancers in men arise in the prostate. It is estimated by the American Cancer Society that 200,000 new cases of prostate cancer will occur in the U.S. in 1994. Prostate cancer is the second leading cause of death from cancer and 38,000 deaths are estimated to occur in 1994. African American men have the highest incidence of prostate cancer in the world, which is almost twice as high as that in white men and more than 600 times higher than in men from Thailand. One in 10 men in the U.S. by age 85 will develop prostate cancer in his lifetime. An estimated 11 million men have latent or clinical prostatic carcinoma. Approximately sixty-five (65%) of the cases already have metastatic disease at the time of diagnosis. The survival rate is less than 20% after metastasis. Web site: http://www.delphion.com/details?pn=US05824488__ •
Male infertility Y-deletion detection battery Inventor(s): First; Marijo Kent (Madison, WI), Muallem; Ariege (Madison, WI) Assignee(s): Promega Corporation (madison, Wi) Patent Number: 5,840,549 Date filed: December 4, 1996 Abstract: The present disclosure discloses a method for probing the integrity of a Y chromosome utilizing multiplex PCR reactions which amplify specific regions of the human Y chromosome which have been linked to normal fertility in human males. The method is capable of detecting deletion mutations within the Y chromosome which are predictive of human male infertility. A kit containing reagents needed to practice the method is also disclosed. Excerpt(s): The present invention relates to detection of deletion mutations in the Y chromosome of human males. More specifically, the present invention relates to a multiplex polymerase chain reaction (PCR) assay for the detection of Y chromosome deletion mutations which are indicative of male infertility. Complete bibliographic citations to the references discussed herein are contained in the Bibliography section, directly preceding the Sequence Listing. Starting in 1905, when Netti Stevens and Edmund Wilson independently described the first direct evidence to support the chromosomal theory of sex determination, researchers have been studying the sex chromosomes to determine the other traits which are controlled by the expression of products encoded on the X and Y chromosomes. For instance, shortly after Stevens' and
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Wilson's experiments, Thomas Hunt Morgan showed that the white-eyed mutation in Drosophila is a sex-linked recessive trait localized to the X chromosome. More recently, with the advent of far more powerful gene mapping tools, many researchers have investigated the Y chromosome to determine those loci responsible for male gonadal development in newborns, and fertility in adult human males. Web site: http://www.delphion.com/details?pn=US05840549__ •
Marker for male infertility and/or fertility Inventor(s): Boue; Franck (15 avenue Raspail, 94250 Gentilly, FR), Sullivan; Robert (3261 Chemin St-Louis, Ste-Foy, Quebec, CA) Assignee(s): None Reported Patent Number: 5,723,305 Date filed: April 18, 1996 Abstract: The present invention relates to a method for the diagnosis of male infertility which comprises the steps of a) determining the amount of P34H in a sperm sample; and b) comparing the determined amount of step (a) with a fertile control sample. The present invention also relates to a kit for the diagnosis of male infertility which comprises an anti-P34H antibody enzyme-labeled, an enzyme substrate and a fertile control sample. Excerpt(s): The invention relates to a marker for male infertility and/or fertility and to a method for the diagnosis of male infertility. Infertility occurs in approximately 8% of North American couples. In 50% of these cases, male factors contribute to this pathological situation. Standard semen analysis including sperm concentration, motility, and morphology are widely used as principal indicators of male fertility. However, these parameters fail to explain all cases of male infertility and do not provide a precise prognostic value of human fertility in vivo or in vitro. Due to the fact that standard semen parameters often provide a poor prognostic value, many other laboratory tests have been developed in order to evaluate the fertilizing ability of human spermatozoa. These include the determination of sperm membrane integrity by hypoosmotic swelling test, nuclear maturity, acrosomal status, motility assessment by video-imaging as well as the ability of sperm to interact with the oocyte. This sperm function has been evaluated by the zona-free hamster test and by the ability of human spermatozoa to bind to homologous zonae pellucida. Therapeutic in vitro fertilization represents a direct evaluation of the fertilizing ability of semen. The prognostic value of the various andrology tests can thus be determined by correlating their conclusions with in vitro fertilization results. The relationship between the different tests and fertilization rates in vitro have shown a very high correlation with the ability of sperm to bind to the zona pellucida, whereas normal morphological sperm and linearity of motility correlated with a lower significance. Other sperm parameters have been shown to be of no prognostic value (Liu D. Y. et al., 1992, Fertil. Steril., 58:465-483). While morphology and linearity are sperm parameters that could easily be assessed, the sperm-zona pellucida binding assay is difficult to perform mainly due to the limited availability of human zonae pellucidae and the technical difficulties associated with a large inter-assay variability. The binding of sperm to the zona pellucida is an absolute prerequisite for fertilization in man as well as in other mammalian species and appears to be speciesspecific. The failure of sperm-zona pellucida binding may be associated with certain cases of male infertility. Therefore, laboratory tests that evaluate the ability of sperm to
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undergo successfully this step in gamete interaction could have clinical usefulness in the diagnosis of male infertility. Web site: http://www.delphion.com/details?pn=US05723305__ •
Method and device for contributing to the obviating of male infertility Inventor(s): Sealfon; Andrew I. (Middletown, NY), Zorgniotti; Adrian W. (New York, NY) Assignee(s): Repro Med Systems, Inc. (middletown, Ny) Patent Number: 4,253,464 Date filed: September 24, 1979 Abstract: Using latent heat of vaporization of a selected evaporative fluid, an abnormally elevated testicular temperature is effectively diminished so as to contribute to obviating male infertility due to poor semen quality. Moreover, the evaporative method employed, and the device using such method, are particularly appropriate in that the cooling effect is achieved over a prolonged period so as to facilitate achieving the desired medical result, whereas merely diminishing the testicular temperature for a short duration would not be medically effective. Excerpt(s): The present invention relates generally to product and method improvements for a recommended treatment for male infertility due to poor semen quality, and more particularly to an effective lower torso garment, and operational mode in a cooling component thereof, for effectively producing an intrascrotal temperature reduction, of as much as 3 degrees centigrade, in the testis. Infertile marriages due to poor semen quality are known to be attributable to an abnormally elevated testicular temperature. As an alternative to a surgical cure, i.e. a varicocelectomy, it is desirable to achieve a temperature reduction of 1 to 3 degrees centigrade, and thus enable the semen to be produced in an optimum temperature range of 31 to 33 degrees centigrade in such infertile males. However, presently known therapeutic wraps or devices for chilling body areas, as exemplified by the wrap of U.S. Pat. No. 4,092,982, are not effective. Not only are such prior art body-chilling devices too cumbersome and uncomfortable for the localized use herein required, but their chilling effect is not compatible with being applied over prolonged periods of treatment, which typically might be as much as 16 hours per day for six to twenty weeks of treatment. The above referred to patented wrap, for example, uses a refrigerant gel which would be too inconvenient to replenish, as well as being otherwise inappropriate, if adopted for the specific end use as above noted. Broadly, it is an object of the present invention to provide a device, effective both in its product and method aspects, for producing a desired intrascrotal temperature reduction overcoming the foregoing and other noted shortcomings of the prior art. Specifically, it is an object to effectively withdraw heat, over a selected prolonged duration, so as to effectuate a correspondingly selected intrascrotal temperature reduction, using a lower torso garment or appliance that offers nominal discomfort or interference with normal activity. Web site: http://www.delphion.com/details?pn=US04253464__
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Method of treating ciliary dyskinesia with uridine triphosphates and related compounds Inventor(s): Boucher, Jr.; Richard C. (Chapel Hill, NC), Drutz; David J. (Chapel Hill, NC), Geary; Cary (Seattle, WA), Jacobus; Karla M. (Cary, NC), James; Michael K. (Raleigh, NC), Lazarowski; Edwardo R. (Chapel Hill, NC), Pendergast; William (Durham, NC), Rideout; Janet L. (Raleigh, NC), Stutts; Monroe Jackson (Chapel Hill, NC), Yerxa; Benjamin R. (Raleigh, NC) Assignee(s): Inspire Pharmaceuticals, Inc. (durham, Nc), The University of North Carolina at Chapel Hill (chapel Hill, Nc) Patent Number: 6,420,347 Date filed: July 17, 1998 Abstract: A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5'triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal spray or nasal or eye drops), oral, inhaled by nebulization, topical, injected, suppository, intra-operative by instillation or application, or ex vivo direct application to spermatozoa. Excerpt(s): This invention relates to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, or ears of a patient by administering certain uridine, adenosine, or cytidine triphosphates. Mucociliary clearance is an important defense mechanism of the human airway and middle/inner ear tract. Coordinated beats of cilia in the nose, trachea, bronchi, and middle ear propel the mucous layer toward the pharynx, carrying along with it microorganisms and other particles captured in the mucus. Normal function of this system depends on the frequency and coordination of ciliary beating and the properties of mucus. There are three components of the mucociliary clearance system: (1) the mucin layer, which is formed by secretion of mucins by goblet cells, (2) cilia, which transport the overlying mucin layer by synchronous beating, and (3) the periciliary liquid layer, which surrounds the cilia and is less viscous than the mucin layer, allowing free movement of the cilia. The electrolyte and water concentration of the periciliary layer is regulated by the luminal epithelial cells. (R. Boucher, et al., Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology, p. 525-32 entitled "Mechanisms and Therapeutic Actions of Uridine Triphosphates in the Lung" (L. Belardinelli, et al. ed., Alumwer Academic Publishers, Boston 1995)). Primary ciliary dyskinesia (PCD) is a congenital disease characterized by ultrastructural defects and motility disturbances of cilia, resulting in either absent or abnormal ciliary movement. The most common clinical manifestations of PCD are chronic respiratory disease (e.g., sinusitis, rhinitis, and bronchiectasis) and otitis media. Because PCD patients have either absent or severely impaired mucociliary clearance (MCC), the only available mechanism to clear or move secretions is cough. Cough clearance may be measured in a manner similar to that previously described for MCC. PCD also impairs the propulsion of spermatozoa, resulting in male infertility. (D.
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Schidlow, Ann Alergy 73(b), 457-68 (1995)). PCD also results in the impairment of cell motility of certain immune system cells, including neutrophils and macrophages. (N. Valerius, Eur j Clin Invest 13, 489-94 (1983)). PCD may be responsible for a form of hydrocephalus caused by ciliary malfunction. (M. Greenstone, Arch Dis Child 59, 481-82 (1984)). The incidence of PCD has been calculated to be one in 16,000 live births, and an estimated 50% of affected individuals also have situs inversus (dextrocardia). The triad of bronchiectasis, sinusitis, and situs inversus (dextrocardia) is referred to as Kartagener's syndrome. (M. Sleigh, Lancet ii, 476 (1981)). It has been hypothesized that Kartagener's syndrome is caused by a lack of embryonic ciliary movement, resulting in the random rotation, of the archenteron such that in half the cases there is situs inversus (dextrocardia) and in the other half there is normal cardia situs. (B. Afzelius Science 193, 317-19 (1976)). The clinical course of PCD is characterized primarily by sinus and ear infections early in life with a progressive change to lung/lower airways diseases in adulthood. Chronic airways infections can lead to chronic obstructive changes in the pulmonary tissue, progressive loss of pulmonary function, and eventually death. Web site: http://www.delphion.com/details?pn=US06420347__ •
Method of treating male infertility Inventor(s): Fahim; Mostafa S. (Columbia, MO) Assignee(s): The Curators of the University of Missouri (columbia, Mo) Patent Number: 4,357,934 Date filed: July 23, 1980 Abstract: Male infertility is treated by increasing the concentration of testosterone in the seminiferous tubules by intratesticular injection of an aqueous suspension of testosterone and/or chorionic gonadotropins without correspondingly increasing the testosterone level in the blood plasma and thereby without substantially interfering with the secretion of the gonadotropins FSH and LH by the pituitary. Excerpt(s): The present invention relates to a method for treating normogonadotropic idiopathic oligospermia and asthenospermia in males. It is generally accepted that the continued secretion by the pituitary gland of the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), is responsible for the development and maintenance of spermotogenesis and for the development and subsequent functional maintenance of the testicular interstitial or Leydig cells. It is also generally accepted that ther is an endocrine feedback system between the pituitary gland and the testes. In the past, testosterone and/or gonadotropins have been administered systemically, usually by intramuscular injection, in the treatment of male infertiliy. Such administration, however, usually increases the plasma level of testosterone which suppresses further release of the gonadotropins by the pituitary. Hence even though the testosterone level in the seminiferous tubules may be increased, the gonadotropins necessary for sperm cell maturation are decreased. The net effect of such systemic treatments varies from patient to patient and is very difficult to control. Web site: http://www.delphion.com/details?pn=US04357934__
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Methods for diagnosing human male infertility Inventor(s): Brown; David B. (1216 Pin Oak Dr., Dickinson, TX 77539) Assignee(s): None Reported Patent Number: 5,770,363 Date filed: June 7, 1995 Abstract: A method for determining the capacity of a human sperm to fertilize a human egg is described by assessing sperm activation events in an in vitro assay using a nonmammalian egg extract, particularly a Xenopus laevis frog egg extract. Fertilizing capacity is assessed as a comparison of sperm decondensation, DNA synthesis and/or sperm recondensation as between a test sperm sample sperm and fertile sperm, such as a sperm sample from a proven fertile human male. The method employs results from the in vitro assay to also determine relative sufficiency or insufficiency of a sperm sample for fertilizing a human egg in human couples with a history of a diagnosed unexplained infertility from standard infertility diagnostic tests. The method may also be used to screen human sperm donors in human artificial insemination programs. A fixed-slide cytoprep sperm analysis of decondensed sperm chromatin, as between a sperm test sample and a sperm sample from a proven fertile human male, may also be used to confirm in vitro decondensation results of the infertility or fertility of a particular human male. A kit is also provided for testing male sperm samples for human egg fertilizing capacity. A process for snap-freezing egg extract without loss of human sperm activation. Event supporting activity is also provided. Excerpt(s): The present invention relates to the field of diagnostic tests for determining if a human male is infertile. More specifically, the present invention provides a method for identifying infertile males by assessing the ability of a particular human sperm sample to fertilize a human egg. The invention also relates to the field of screening protocols, as a method for screening human sperm samples for use in human fertilization is also provided. The invention also relates to the field of diagnostic kits, as a kit for detecting male infertility is also disclosed. The term "unexplained infertility" is applied to virtually any clinically inexplicable failure of a male and female couple to conceive after extensive fertility testing of both partners reveals no identifiable cause for the couples infertility. When a couple is found to be "normal" in their standard fertility evaluation (i.e., female post-coital tests, timed endometrial biopsy, hysterosalpingogram, laparoscopy, male, "normal" sperm analysis, with sperm counts greater than 20 million/ml on at least two occasions, total sperm numbers of 40 million or more, sperm motility greater than 60%, and normal morphology in more than 60% of the sperm.sup.4), and the couple has had a history of involuntary infertility for at least 2 years, a human couple is diagnosed unsatisfactorily as "unexplainably infertile." Such couples historically undergo numerous invasive, protracted and expensive assisted reproductive technology attempts in their pursuit of pregnancy. Although numerous tests are available for diagnosing infertility problems, 16% of all couples who seek medical treatment are diagnosed with unexplained infertility. Male members of inexplicably infertile couples produce sperm that appear normal in standard semen analyses that include assessment of sperm density, progressive motility, sperm morphology and semen volume. Since these methods have limited capacity for evaluating male fertility, other tests have been developed including: quantitative ultramorphology (QUM) using transmission and scanning electron microscopy.sup.109; in vitro nuclear chromatin decondensation (NCD) analysis.sup.110; and the sperm chromatin structure assay (SCSA;.sup.111). Tests of human sperm function have also been developed, including: videomicrographic assessment of motility (straight line and
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curvilinear velocity, and amplitude of lateral head displacement); analysis of membrane integrity; tests for sperm nuclear maturity; measurements of acrosomal status; acrosome reaction and acrosin activity; and the analysis of sperm penetration of hamster zona-free ova (sperm penetration assay; SPA); and zona binding. However, except for the SPA, none of these tests directly assay sperm activation events that occur after the sperm nucleus enters into the egg, a series of events critical for the entry of the zygote into the developmental program. Web site: http://www.delphion.com/details?pn=US05770363__ •
Pyridylalkyl phenyl ureas and their N-oxides Inventor(s): Callahan; William A. (Kalamazoo, MI), Glenn; Eldridge Myles (Kalamazoo, MI), Rector; Douglas L. (Parchment, MI) Assignee(s): The Upjohn Company (kalamazoo, Mi) Patent Number: 4,001,256 Date filed: June 25, 1975 Abstract: A method of improving the endogenous production of prostaglandins by a mammal is disclosed, which comprises administering to the mammal an effective amount of certain 1-pyridylalkyl-3-phenylureas. Disclosed also are novel substituted 1pyridylalkyl-3-phenylureas and therapeutic compositions thereof which are useful in carrying out the method of the invention.Disclosed also are methods of treating mammals for clinical conditions responsive to prostaglandins, such as, for example, male infertility, epidermal injuries, atonic uterine bleeding, thromboembolic disease and like clinical conditions. Excerpt(s): The invention is concerned with the production of endogenous prostaglandins by mammals and more specifically concerns a method of raising prostaglandin production levels in the mammal by administering 1-pyridylalkyl-3phenylureas. The invention also concerns a novel group of substituted 1-pyridylalkyl-3phenylureas and therapeutic compositions thereof. Natural prostaglandins are a wellknown group of physiologically active unsaturated hydroxy-substituted fatty acids which are biosynthesized endogenously by mammals such as, for example, canines, bovines, equines, swine, and humans. Identified roles of the natural prostaglandins in mammalian physiology are illustrated by their action as mediators in the inflammatory process, as tonal agents in effecting the contractility of smooth muscle and as activators in a wide variety of mammalian reproductive processes. Structurally, the natural prostaglandins have been arbitrarily classified into four basic families termed "PGE", "PGF", "PGA", and "PGB", respectively. The various families are composed of differing analogs and stereoisomers having as a hypothetical parent structure, prostanoic acid. For example, the principal members of the PGE family are 11.alpha. ,15-hydroxy-9-ketoprosta-13-enoic acid (referred to alternatively for convenience as "PGE.sub.1 "); 11.alpha.,15-dihydroxy-9-keto-prosta-5,13-dienoic acid (hereinafter referred to alternatively as "PGE.sub.2 "); and 11.alpha.,15-dihydroxy-9-keto-prosta-5,13,17-trienoic acid (referred to alternatively for convenience as "PGE.sub.3 "). The principal members of the PGF family are 9.alpha. ,11.alpha.,15-trihydroxy-prosta 13 enoic acid (referred to alternatively for convenience as "PGF.sub.1.alpha."); 9.beta.,11.alpha.,15-trihydroxyprosta-13-enoic acid (referred to alternatively for convenience as "PGF.sub.1.beta."); 9.alpha.,11.alpha.,15-trihydroxy-prosta-5,13-dienoic acid (hereinafter referred to alternatively for convenience as "PGF.sub.2.alpha."); 9.beta.,11.alpha.,15-trihydroxyprosta-5,13-dienoic acid (referred to alternatively as "PGF.sub.2.beta."); and
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9.alpha.,11.alpha.,15-trihydroxy prosta-5,13,17-trienoic acid (referred to alternatively as "PGF.sub.3.alpha."). Web site: http://www.delphion.com/details?pn=US04001256__ •
Treatment of male infertility by administration of a muellerian inhibiting substance and surgery and/or hormonal treatment Inventor(s): Donahue; Patricia K. (Weston, MA), Hutson; John M. (East Malvern, AU) Assignee(s): The University of Melbourne (parkville, Au) Patent Number: 5,484,768 Date filed: March 8, 1993 Abstract: A method for the treatment of infertility associated with undescended testes in male animals is disclosed. Also disclosed is a method for effecting testicular germ cell maturation.These methods involve administering to a subject in need of such treatment a therapeutically effective amount of Mullerian inhibiting substance (MIS) or an analogue thereof having MIS activity.MIS may be administered to a subject shortly after treatment to effect testes descent and/or prior to testes descent. Excerpt(s): This invention relates to a method for the treatment of male infertility associated with undescended testes. The testes are two glandular organs which secrete semen, and are situated in the scrotum, being suspended by the spermatic cords. For the last 40-50 years it has been known that testicular descent is controlled by male androgenic hormones (testosterone). Androgens were proposed to act directly or indirectly on mesenchymal tissue in the groin known as the gubernaculum, which migrates across the pubic region from the groin to the scrotum during inguino-scrotal testicular descent. The gubernaculum was thought to guide the testes into the scrotum. Web site: http://www.delphion.com/details?pn=US05484768__
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Zinc salt of fructose-1,6-diphosphate Inventor(s): Vinas; Antonio B. (Barcelona, ES) Assignee(s): Laboratrios Vinas, S.a. (barcelona, Es) Patent Number: 4,873,223 Date filed: March 12, 1986 Abstract: The zinc salt of fructose-1,6-diphosphate, a pharmaceutical composition including the salt and a method of treating male infertility due to Zn, fructose deficiencies in the seminal plasma or inversion of testicular function due to old age in a patient. Excerpt(s): This invention has a series of advantages because of the applications which can be derived from the therapeutic viewpoint. In fact, the compound thus obtained contains in its formula the zinc (Zn.sup.+2) divalent cation and the fructose-1,6diphosphate moiety. Therefore the administration of the compound, the zinc salt of fructose-1,6-diphosphate, at dosages which can vary under the medical formulation according to the selected route of administration (oral, parenteral, rectal, etc.) allows animals (experimental pharmacology) or humans to make use of both moieties with their corresponding advantages. Zinc has therapeutic effects on the gonadal
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dysfunction. The concentration of zinc in plasma is an important factor in regulating fertility; when the Zn levels in seminal plasma are low, a decrease in the potential fertility in man and secretory male sterility has been observed. The addition of zinc regulates (normalizes) the testosterone in serum and the concentration of the spermatozoa in the ejaculate as well as their motility. For this reason, zinc is believed to be necessary as a favorable medium for the motility and activity of spermatozoa. The bioavailability of zinc has an effect on the activity of some testicular enzymes. Web site: http://www.delphion.com/details?pn=US04873223__
Patent Applications on Male Infertility 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 male infertility: •
Acetylcholinesterase-derived peptides and uses thereof Inventor(s): Deutch, Varda; (Jerusalem, IL), Eldor, Amiram; (US), Eldor, Sofia; ( Tel Aviv, IL), Grisaru, Dan; (Hertzlia, IL), Soreq, Hermona; (Jerusalem, IL) Correspondence: Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030036632 Date filed: November 30, 2001 Abstract: The invention relates to a cell growth and/or differentiation regulatory peptide comprising a sequence of about 9 to about 150 amino acids derived from acetylcholinesterase amino acid sequence, preferably from the C-terminal region of acetylcholinesterase. The invention also relates to pharmaceutical compositions comprising the peptides, particularly for use in promoting survival of stem cells, promoting differentiation of stem cells, promoting growth of stem cells and/or promoting the growth-enhancing effect of a growth factor on stem cells, alone, or in combination with other growth factors. Of particular interest is the use of the peptides in the treatment of thrombocytopenia, post-irradiation conditions, post-chemotherapy conditions, or conditions following massive blood loss and promotion of neural progenitors in use for cell therapies aimed at restoring neural functions in diseased individuals. Further, the invention relates to antibodies against the peptides, inter alia for diagnostic use, for example, the diagnosis of stress-induced male infertility. The invention also relates to in vitro and in vivo methods for screening of drugs that affect the central nervous system, and are potential modulators of interactions between the "readthrough" form of acteylcholinesterase, AChE-R, the intracellular receptor RACK1 and the kinase PKC. Excerpt(s): This application is a continuation-in-part application of international patent application PCT/IL00/00311. The invention is directed to the field of stem cell survival and expansion. Specifically, the invention is directed at the stem cell survival and expansion effects of peptides derived from acetylcholinesterase. In addition, the invention relates to a system for screening of nervous system drugs that are directed to
10
This has been a common practice outside the United States prior to December 2000.
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central nervous system conditions or disorders. More specifically, the invention relates to the screening of modulators of the AChE-R-PKC.beta.II-RACK1 complex. Stress insults evoke a plethora of responses in the organism, affecting the functioning of various systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Activation of the cystic fibrosis transmembrane conductance regulator chloride channel Inventor(s): Cai, Zhiwei; (Bristol, GB), Sheppard, David Noel; (Bristol, GB) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20040006127 Date filed: June 9, 2003 Abstract: Fluorescein and derivatives have use in the treatment of a disease of condition of a living animal body, including human, which disease is responsive to the activation of the cystic fibrosis transmembrane conductance regulator chloride channels, for instance cystic fibrosis, disseminated brocheiectasis, pulmonary infections, chronic pancreatitis, male infertility and long QT syndrome. Excerpt(s): The present invention relates to the activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl.sup.-) channel. More particularly, t relates to members of a defined class of chemical compounds as activators of the CFTR Cl.sup.- channel and the use of these agents in the treatment of diseases caused by the dysfunction of the CFTR Cl.sup.- channel. CFTR (1) forms a Cl.sup.channel with complex regulation (2,3). It is predominantly expressed in the apical membrane of epithelia, where it provides a pathway for the movement of Cl.sup.- ions and a key point at which to regulate the rate of transepithelial salt and water movement (4). CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains' (NBDs), and a regulatory (R) domain (1). The MSDs contribute to the formation of the Cl.sup.--selective pore, while the NBDs and R domain control channel activity (2,3). The activation of the cAMP-dependent protein kinase (PKA) causes the phosphorylation of multiple serine residues within the R domain. Once the R domain is phosphorylated, channel gating is controlled by a cycle of ATP hydrolysis at the NBDs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods of making embryonic stem cells Inventor(s): Hogan, Brigid L.M.; (Brentwood, TN), Zhao, Guang-Quan; (Columbia, MO) Correspondence: Needle & Rosenberg P C; 127 Peachtree Street N E; Atlanta; GA; 303031811; US Patent Application Number: 20030153072 Date filed: January 24, 2003 Abstract: The invention relates to cell proliferation, cell differentiation, male infertility, male fertility and to compositions and methods involved therein.
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Excerpt(s): The field of the invention is human and nonhuman mammalian spermatogenesis. The bone morphogenetic proteins (BMPs) are members of a large, highly conserved, family of extracellular polypeptide signaling molecules related to transforming growth factor.beta.(TGF-.beta.). There is now considerable evidence from expression studies, and from the in vivo effects of misexpression and mutations, that Bmp genes play key roles at many different stages of embryonic development, in both invertebrates and vertebrates (Kingsley et al., 1994, Dev. Biol. 166:112-122; Massague et al., 1994, Trends Cell Biol. 4:172-178; Hogan, 1995, Sem. Dev.Biol. 6:257-265). In the mouse, both spontaneous and induced mutations in a number of Bmp genes have shed light on their function in vivo. The first example to be described was a series of short ear mutations, which result from alterations in the Bmp5 gene (Green, 1968, J. Exp. Zool. 167:129-150; Kingsley et al., 1992, Cell 71:399-410; King et al., 1994, Dev. Biol. 166:112122). Null mutants are viable, but have defects in cartilage development in specific parts of the skeletal system, as well as abnormalities in the lung, kidney and ureter in some genetic backgrounds. Mutations in other Bmp genes have been generated by homologous recombination in embryonic stem cells. For example, Bmp7 homozygous null mutant mice die shortly after birth with major defects in eye, kidney and limb development (Dudley et al., 1995, Genes Dev. 9:2795-2807; Luo et al., 1995, Genes Dev. 9:2808-2820). Most Bmp4 homozygous mutant embryos die around the time of gastrulation and many exhibit a deficiency in extraembryonic and posterior/ventral mesoderm (Winnier et al., 1995, Genes Dev. 9:2105-2116), a finding consistent with the effect of BMP4 on mesoderm patterning in Xenopus embryos (Jones et al., 1992, Development 115:639-647; Graff et al., 1994, Cell 79:169-179; Harland, 1994,Proc. Natl. Acad. Sci. USA 91:10243-10246). Mutations have also been described in other members of the BMP superfamily, including mouse nodal, and Gdf5 (brachypodism) (Zhou et al., 1993, Nature 361:543-547; Conlon et al., 1994, Development 120:1919-1928; Storm et al., 1994, Nature 368:639-643). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
DESERT HEDGEHOG RELATED NUCLEIC ACIDS AND PROTEINS Inventor(s): EDMONDS, BRIAN TAYLOR; (CARMEL, IN) Correspondence: Eli Lily And Company; Lilly Corporate Center; Patent Divsion Dc: 1104; Indianapolis; IN; 46285 Patent Application Number: 20020026043 Date filed: February 4, 1999 Abstract: The invention provides isolated nucleic acid, proteins and peptides, wherein said proteins and peptides are related to the Hedgehog family of proteins. Also provided are vectors and transformed host cells for expressing said proteins, and a method for identifying compounds that bind and/or modulate the activity of said proteins, and pharmaceutical compositions and methods for treating spinal cord injury, male infertility, and tumor growth. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/073,878, filed Feb. 6, 1998; No. 60/076,553, filed Mar. 2, 1998; and No. 60/091,843, filed Jul. 6, 1998. This invention relates to recombinant DNA technology. In particular the invention pertains to a Hedgehog-related nucleic acids from a human source, as well as proteins and/or peptides encoded thereby, and related thereto. Also contemplated are methods for identifying compounds that bind said proteins, and methods for treating a variety of abnormal conditions in mammals including humans such as male
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infertility, tumor growth, and spinal regeneration. The hedgehog genes are found in many vertebrate and invertebrate species (See generally, M. Hammerschmidt, A. Brook, and A. McMahon, "The world according to hedgehog" Trends in Genetics, 13, 14-21, 1997). Members of the hedgehog gene family comprise secreted signaling molecules that control a variety of developmental processes. In invertebrates, hedgehog proteins are involved in pattern segmentation; in vertebrates hedgehog related proteins are involved in left-right asymmetry, polarity (in the central nervous system, somites, and limbs), organogenesis, chondrogeneis, and spermatogenesis. The progenitor hedgehog sequence (designated hh), first identified in Drosophila melanogaster, affects embryonic and larval development. Later investigations have revealed homologs to the hh sequence in vertebrates, including mammals. One hh homolog, termed Sonic hedgehog (Shh), has been found in mouse, human, rat, Xenopus, chicken and Zebrafish (See e.g. Chang et.al. Development, 120, 3339-53, 1994; Ekker et.al. Development, 121, 23337-47, 1995; Krauss et.al. Cell, 75, 1431-44, 1993; Riddle et.al. Cell, 75, 1401-16, 1993); another hh homolog, termed Indian hedgehog (Ihh), has been found in mouse, human, and chicken; a third homolog, termed Desert hedgehog (Dhh), has been found thus far only in mouse; a fourth homolog, termed Banded hedgehog (X-bhh), has been found only in Xenopus; a fifth, termed Cephalic hedgehog (X-chh), has been found so far only in Xenopus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Genetic testing for male factor infertility Inventor(s): Dix, David Jacob; (Raleigh, NC), Krawetz, Stephen A.; (Detroit, MI), Miller, David; (Leeds General Infirmary, GB) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001; US Patent Application Number: 20030108925 Date filed: October 4, 2002 Abstract: Genetic testing for male infertility or damage to spermatozoa is accomplished by providing a microarray of DNA probes with a sample of spermatozoa to determine the mRNA fingerprints of the sample; and comparing the mRNA fingerprints of the sample with the mRNA fingerprints of normal fertile male spermatozoa. Excerpt(s): The present invention claims priority from provisional application Serial No. 60/327,525, filed Oct. 5, 2001, the entire contents of which are hereby incorporated by reference. The present invention relates to methods, kits, and tools for determining fertility of a male. Specifically, the present invention relates to a method for determining male fertility through genetic analysis to determine function of spermatozoa. Predicting the fertility of a male is very useful in a variety of contexts. For example, the artificial insemination industry is interested in knowing the likelihood that fertilization will occur if a female is artificially inseminated with a particular male's semen. Alternatively, human fertility clinics are concerned with achieving impregnation, and evaluating the sperm count of a male is one step in this procedure. Thus, whether in the context of animal breeding, the artificial insemination industry, or human fertility clinics, determination of the fertility of the male is very important. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human PEM as a target for birth contol and treatment of Alzheimer's disease Inventor(s): Geserick, Christoph; (Berlin, DE), Haendler, Bernard; (Berlin, DE), Weiss, Bertram; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020048764 Date filed: May 31, 2001 Abstract: The invention relates to the human PEM polypeptide that plays an important role for the maturation of sperm and for Alzheimer's disease, and the nucleic acid that codes for them. The invention comprises the use of PEM as a target in male birth control and for the treatment and diagnosis of male infertility and Alzheimer's disease. The invention also includes a selection process for PEM antagonists as well as the production of binding molecules, which specifically detect PEM. In addition, genes that are regulated by the PEM gene are part of this invention. Excerpt(s): The invention relates to the human PEM polypeptide, which plays an important role for the maturation of sperm and the nucleic acid that codes for them. The invention comprises the use of PEM as a target in male birth control and for the treatment and diagnosis of male infertility and Alzheimer's disease. The invention also includes a selection process for PEM antagonists as well as the production of binding molecules, which specifically detect PEM. In addition, genes that are regulated by the PEM gene are part of this invention. The intention to use proteins of the male reproductive tract or sperm proteins as a target group for non-hormonal contraception has been known for several decades. For example, a project with the name "Vaccines for Fertility Regulation" was supported by the World Health Organization (WHO) (P. D. Griffin, Hum. Reprod., 1991, 6: 166-172). Various sperm proteins such as, e.g., PH-20, SP10, FA-1, FA-2, CS-1, NZ-1, NZ-2 and lactate-dehydrogenase C4 were proposed as candidates for immunocontraception (R. K. Naz, Immunol. Rev., 1999, 171: 193-202). Immunization tests with PH-20 showed that both male and female animals are thus completely and reversibly infertile (P. Primakoff et al., Nature, 1988, 335: 543-546). The use of the intra-acrosomal sperm protein SP-10 as an antigen caused an immunological response in women that reduces fertility (R. W. Wright et al., Biol. Reprod., 1990, 42: 693-701). Active immunization of animals with FA-1 produces a lasting and reversible inhibition of fertility (R. K. Naz and X. Zhu, Biol. Reprod., 1998, 59: 1095-1100). PEM is a transcription factor that includes the Homeobox family. The corresponding cDNA was cloned from the mouse (M. F. Wilkinson et al., Dev. Biol., 1990, 141: 451-455) and from the rat (S. Maiti et al., J. Biol. Chem., 1996, 271: 17536-17546). PEM transcripts are expressed abundantly and selectively in the male genital tract. In the mouse, the PEM expression was mainly detected in the testes, while in the rat, PEM can mainly be found in the epididymis (K. A. Sutton et al., J. Androl., 1998, 19: 21-30). The in vivo expression of the PEM gene is regulated in these organs by androgens. In addition, PEM transcripts were described in the muscle and in macrophages, but in these cases, the PEM expression does not seem to be regulated by androgens, which can be attributed to the use of different promoters (S. Maiti et al., J. Biol. Chem., 1996, 271: 17536-17546). Despite the unremarkable phenotype of the PEM-knock-out mouse (J. L. Pitman et al., Dev. Biol., 1998, 202: 196-214), it can be assumed that the human PEM plays an essential role in spermatogenesis and/or in sperm maturation. PEM is the sole known transcription factor whose expression is regulated by androgens (S. Maiti et al., J. Biol. Chem., 1996, 271: 17536-17546).
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Human zona pellucida proteins and methods of their use in diagnoising male infertility Inventor(s): Cheng, Jr-Gang; (Virginia Beach, VA), Chi, Ting-Fung; (Yorktown, VA), Dong, Ke-Wen; (Chesapeake, VA), Hsu, Ming-I; (Virginia Beach, VA), Lin, Zhiyong; (Norfolk, VA), Zheng, Heming; (Norfolk, VA) Correspondence: Heller Ehrman White & Mcauliffe Llp; 1666 K Street,nw; Suite 300; Washington; DC; 20006; US Patent Application Number: 20030148930 Date filed: August 1, 2002 Abstract: Reagents, methods, and kits are described that are useful for fertility testing and that in many cases provides much faster, convenient and rapid determination of male infertility. The reagents described include properly glycosylated human ZP3, ZP2, ZP1, glycosylated peptides thereof, fusion proteins such as green fluorescent protein-ZP3, non-covalent complexes of ZP2 with ZP3, fusion protein of ZP2-ZP3, solid phase materials such as agarose beads coated with binding agents such as ZP3, and other artificial zona. Methods are provided that, in many cases convert a complex biological event into a well defined biochemical binding event based on one or more of the reagents. Such methods are much easier to set up and monitor, allowing more convenient and inexpensive diagnostic testing for male fertility. The acrosome reaction is detected in other embodiments by virtue of quantitating one or more released substances. Kits are further provided that contain one or more reagents useful for testing at a diagnostic laboratory or other facility. Excerpt(s): The invention relates to diagnosis of male infertility and more specifically to the use of ZP2 and ZP3 proteins in diagnostics. Infertility is a significant medical problem affecting a large proportion of the population. About half of the causes of infertility arise in the male (generally the sperm or seminal fluid) and usually no specific cause can be identified, even after thorough evaluation. Several diagnostic tests for such evaluations have been developed and provide some useful information. Generally, studies of patients having unexplained infertility using these tests have reported defects in capacitation and sperm motion characteristics, binding of spermatozoa to the zona pellucida, acrosome reaction, acrosin activity of spermatozoa, and the ability of the spermatozoa to penetrate zona-free oocytes (Mackenna et al, 1995). However, only when such tests identify one or more abnormalities can more specific and cost-effective treatment regimens be instituted (Chuang et al, 1998). An important clinical test for evaluation of male fertility uses the acrosome reaction whereby acrosin and other acrosome enzymes in sperm are released by simulation of contact with an egg or by actual contact with an egg. Almost all methods for detecting the acrosome reaction monitor a morphological change during the acrosome reaction. The most widely used methods utilize optical microscopy, wherein spermatozoa are visualized after staining. Different chemical agents such as calorimetric dyes and fluorophore labeled lectins and antibodies may be used. However the results of these tests often differ depending on the characteristics of the different agents used. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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In vitro production of haploid germ cells Inventor(s): Kaproth, Michael T.; (Ithaca, NY), Lee, Dong Ryul; (Seoul, KR), Parks, John E.; (Ithaca, NY) Correspondence: Michael L. Goldman, ESQ.; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030027329 Date filed: May 16, 2002 Abstract: The present invention relates to a method of in vitro spermatogenesis involving Sertoli cells and diploid germ cells from a testis of a male mammal to yield differentiated haploid spermatids. The present invention also relates to spermatids produced by the method described above, where the spermatids are haploid. The present invention also involves a method of overcoming male infertility in mammals involving the use of the haploid round spermatids produced by the in vitro spermatogenesis method of the present invention. The present invention also relates to isolated haploid spermatids. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/292,032, filed May 18, 2001. The present invention relates to a method of in vitro spermatogenesis. The present invention also relates to methods of overcoming male infertility of mammals using the in vitro spermatogenesis method of the present invention. The present invention further relates to an isolated haploid spermatid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compounds for modulating male fertility Inventor(s): Korneluk, Robert G.; (Ottawa, CA), Lagace, Mark; (Ottawa, CA) Correspondence: Clark & Elbing Llp; 176 Federal Street; Boston; MA; 02110-2214; US Patent Application Number: 20020086409 Date filed: December 18, 2001 Abstract: The invention features methods and reagents useful for the treatment of excessive or insufficient apoptosis in cells, and, particularly, in germ-line cells. The invention is useful in treating testicular cancers, cancers of germ-line cells, cancers in non-germ-line cell tissues, infertility (e.g., male infertility), and for birth control (e.g., male birth control). Excerpt(s): This application claims priority from co-pending U.S. Utility application Ser. No. 09/239,867, filed Jan. 29, 1999, which claims benefit from U.S. Provisional Application Ser. No. 60/073,001, filed Jan. 29, 1998 (now abandoned). The invention relates to apoptosis in cells, particularly cell involved in fertility. Apoptosis is a fundamental process of cell death required for the elimination of unwanted cells in multicellular organisms and involves an ordered cascade of events leading to hallmark morphological changes including nuclear condensation, chromosome laddering, and membrane blebbing. In one specific example, apoptosis plays a prominent role during all stages of sperm development. Spermatogenesis is a process that results in the generation of mature sperm cells from primary germ cells, and some of the events affected by apoptosis include the elimination of unwanted cells and the prevention of the death of those cells destined to become functional sperm (Hsueh et al., Recent Prog. Horm. Res. 51: 433, 1996; Furuchi et al., Development 122: 1703, 1996).
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Sperm quality assay Inventor(s): Sutovsky, Peter; (Aloha, OR) Correspondence: J. Mitchell Jones; Medlen & Carroll, Llp; Suite 350; 101 Howard Street; San Francisco; CA; 94105; US Patent Application Number: 20030235870 Date filed: May 6, 2003 Abstract: The present invention relates to male infertility, and in particular to assays for predicting fertility in animals including human and bovines. In some embodiments, semen samples are evaluated by measuring the amount of ubiquitin in the sample, and in particular by measuring the extent of ubiquitination spermatozoa. Increased levels of ubiquitination in a sample are correlated with lower fertility. Ubiquitination may be assayed by several methods, including immunocytochemical measurement, ELISA, and flow cytometry. Excerpt(s): The present invention relates to male infertility, and in particular to assays for determining fertility. Infertility is diagnosed as the failure to become pregnant after one year of regular, unprotected intercourse. About ten percent of couples are infertile. Male factor infertility is the sole or contributing cause in about forty percent of these cases. In 1995, approximately 60,000 cycles of ART (Advanced Reproductive Technology) were performed in the United States to treat infertility. Of these procedures, approximately 90% involved in vitro fertilization at an average cost of $7,800.00 per cycle. Semen analysis forms the basis of the initial evaluation for assessing male-factor infertility. In general, two to three semen analyses are performed because semen quality normally fluctuates for a given individual. Subjects are normally encouraged to refrain from intercourse for 2 to 3 days prior to evaluation. Abstinence for a shorter time can decrease ejaculate volume, while prolonged abstinence can impair sperm motility. Traditional semen analysis evaluates a number of parameters, including, ejaculate volume, sperm count, sperm motility, forward progression, sperm morphology, pH, agglutination, leukospermia, and viscosity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Substituted imidazoles as selective modulators of bradykinin B2 receptors Inventor(s): DeSimone, Robert; (Durham, CT), He, Xiao-shu; (Branford, CT), Hodgetts, Kevin J.; (Killingworth, CT), Hutchison, Alan; (Madison, CT), Maynard, George D.; (Clinton, CT), Rachwal, Stanislaw; (Branford, CT), Shaw, Kenneth; (Weston, CT) Correspondence: Leslie-anne Horvath; Patent Department; Neurogen Corporation; 35 NE Industrial RD.; Branford; CT; 06405; US Patent Application Number: 20020115693 Date filed: January 17, 2001 Abstract: Disclosed are compounds of the formula: 1or the pharmaceutically acceptable non-toxic salts thereof wherein Y, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7 R.sub.7' are variables defined herein, which compounds are modulators of Bradykinin B.sub.2 receptors. These compounds are therefore useful in the diagnosis
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and treatment of renal diseases, heart failure, hypertension, Meniere's disease, vaginal inflammation and pain, peripheral circulatory disorders, climacteric disturbance, retinochoroidal circulatory disorders, myocardial ischemia, myocardial infarction, postmyocardial infarction syndrome, angina pectoris, restenosis after percutaneous transluminal coronary angioplasty, hepatitis, liver cirrhosis, pancreatitis, ileus, diabetes, diabetic complications, male infertility, glaucoma, pain, asthma, and rhinitis, and for the increase of permeability of the blood-brain barrier or the blood-brain-tumor barrier. Excerpt(s): This application claims priority from U.S. provisional patent application no. 60/176,869, filed Jan. 18, 2000. This invention relates to certain imidazoles which, when appropriately substituted, are selective modulators of Bradykinin B.sub.2 receptors (BK2 receptors). This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of central and peripheral disorders. Additionally, compounds of this invention are useful as positive controls in assays for BK-2 receptor activity and when appropriately labeled as probes for the localization of BK-2 receptors in tissue sections. Bradykinin (BK), a nonapeptide, and the closely related decapeptide kallidin (Lys-BK), are produced by proteolytic cleavage of high molecular weight kininogen by plasma kallikreins. The effects of bradykinin and kallidin are mediated by specific seven transmembrane Gprotein coupled receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Variant cleavage stimulation factor and its encoding nucleic acid Inventor(s): Wallace-Shannon, Allison Michelle; (The Woodlands, TX), Dass, Brinda; (Lubbock, TX), MacDonald, Clinton C.; (Lubbock, TX) Correspondence: Michael L. Goldman, ESQ.; Nixon Peabody Llp; Clinton Square; P.O. Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030215833 Date filed: December 9, 2002 Abstract: The present invention relates to an isolated human nucleic acid molecule encoding a protein or polypeptide which controls RNA polyadenylation, an isolated mouse nucleic acid molecule encoding a protein or polypeptide which controls RNA polyadenylation, and nucleic acid constructs, host cells and an expression system incorporating the nucleic acid molecules. The present invention also discloses methods of diagnosing male infertility; a method of contraception for mammals; and a method for diagnosing a cancerous condition in a subject using the nucleic acid molecules and proteins of the present invention. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/338,672, filed Dec. 11, 2001. The present invention relates to an isolated nucleic acid molecule encoding a variant of the human cleavage stimulation factor (hCstF-64) polyadenylation protein, h.tau.CstF-64; an isolated mouse nucleic acid molecule encoding the variant of the murine cleavage stimulation factor (mCstF-64) polyadenylation protein, m.tau.CstF-64; and methods of use for the nucleic acid molecules and the proteins in diagnosis and treatment of male infertility. Polyadenylation is the process of eukaryotic mRNA processing in which 3' end cleavage occurs, followed by the addition of as many as 250 adenosine residues. Messenger RNA polyadenylation is important for cellular processes including transcription termination, splicing, mRNA transport, translation, and mRNA stability. Polyadenylation requires at
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least five protein complexes, including the cleavage and polyadenylation specificity factor (CPSF), the cleavage stimulation factor (CstF), two cleavage factors (CFI and CFII), and the poly (A) polymerase. Other factors, including the poly(A)-binding protein II (which mediates poly(A) tail length), the U1A small nuclear ribonucleoprotein (SnRNP) (which interacts with both CPSF and the poly(A)polymerase) and DSEF-1 (which binds G-rich auxiliary elements), also contribute to efficient polyadenylation. 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 male infertility, 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 “male infertility” (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 male infertility. You can also use this procedure to view pending patent applications concerning male infertility. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON MALE INFERTILITY Overview This chapter provides bibliographic book references relating to male infertility. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on male infertility include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “male infertility” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on male infertility: •
Urology for Primary Care Physicians Source: Philadelphia, PA: W.B. Saunders Company. 1999. 399 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $52.00 plus shipping and handling. ISBN: 0721671489. Summary: The intent of this book is to present from the urologist's perspective the most cost effective and appropriate approaches for the primary care physician to evaluate and treat or triage patients with urologic problems in the office or emergency department. The book offers a systematic, problem oriented approach and a capsular presentation of highlights and 'take home' messages. The text includes 31 chapters: the anatomic basis of common urologic diseases, a systematic approach to urologic evaluation, laboratory investigations in urology, principles of imaging studies of the genitourinary system,
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urologic emergencies, the evaluation and management of hematuria (blood in the urine), genitourinary tract trauma, urinary calculus disease, sexually transmitted diseases, upper urinary tract infections (UTIs), UTIs in children, lower UTIs in women, lower UTIs in men, uncommon infections of the genitourinary tract, voiding dysfunction and urinary incontinence in women, voiding dysfunction in men with lower urinary tract symptoms and benign prostatic hyperplasia (BPH), benign prostatic hypertrophy, urologic problems in pregnancy, renal (kidney) function in pregnancy, perinatal urologic consultation, congenital anomalies, pediatric enuresis (bedwetting) and voiding dysfunction, genitourinary malignancies (cancer) in children, prostate specific antigen (PSA), carcinoma of the genitourinary system, the role of primary health care providers in cancer prevention, acute renal failure (ARF), endocrine and metabolic disorders, management of male infertility, sexual dysfunction in the male, and superficial lesions of the male external genitalia. Each chapter includes black and white illustrations and a list of suggested readings. A subject index concludes the text. •
20 Common Problems in Urology Source: New York, NY: McGraw-Hill, Inc. 2001. 335 p. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070634130. Summary: This text on common problems in urology is designed for the primary care provider. The text covers both pediatric and adult conditions and features quick reference algorithms, charts and tables that organize presenting signs and symptoms, diagnostic tests, and treatments. Twenty chapters cover fetal and postnatal hydronephrosis (fluid accumulation in the kidneys), urinary tract infections (UTIs) in children, cryptorchidism (undescended testicles), circumcision, nocturnal enuresis (bedwetting), UTIs in adults, urethritis, urinary incontinence, interstitial cystitis, geriatric urology, hematuria (blood in the urine), prostate cancer screening, benign prostatic hyperplasia (BPH), scrotal mass and pain, genital skin rash, urinary calculi (stones), erectile dysfunction (impotence), male infertility, vasectomy, male menopause, and imaging studies (diagnostic tests). Most chapters define the condition and then discuss the differential diagnosis, the physical examination, recommended diagnostic tests, special considerations, treatment options, and patient care strategies. The text also offers practice advice on when to refer to a specialist and what to expect post-referral. The text concludes with a subject index and is illustrated with black and white photographs and diagrams.
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Comprehensive Urology Source: Orlando, FL: Mosby, Inc. 2001. 704 p. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail:
[email protected] Website: www.elsevierhealth.com. PRICE: $249.00. ISBN: 723429499. Summary: This textbook offers a comprehensive overview of urology in one volume incorporating clinical information concerning all aspects of urology. The internationally renowned contributors present detailed clinical information in a format which is not encyclopedic but contains carefully selected and nonbiased practical information backed by specific, relevant references. The first section concisely reviews basic anatomy, physiology, and molecular biology, which have relevance for the entire text. The
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remaining 42 chapters are presented in seven sections: investigative urology, pediatric urology, benign conditions of the upper urinary tract, urologic oncology, benign conditions of the lower urinary tract, andrology, and miscellaneous. Specific topics include diagnostic tests, interventional uroradiology, congenital diseases, vesicoureteral reflux, renal (kidney) transplantation, urinary tract infections, urinary tract stones, bladder cancer, prostate cancer, benign prostatic hyperplasia, female urology and incontinence, interstitial cystitis, the neuropathic bladder, urinary diversion and augmentations, urethral stricture disease, male infertility, erectile dysfunction, benign and malignant disorders of the penis, extracorporeal shock wave lithotripsy (ESWL), genitourinary trauma, radiation therapy, and chemotherapy. Each chapter concludes with lengthy references, and a subject index concludes the volume. The text is illustrated with full-color photographs and drawings. •
Smith's General Urology. Fifteenth Edition Source: Columbus, OH: McGraw-Hill, Inc. 2000. 868 p. Contact: Available from McGraw-Hill. Medical Publishing. 1221 P.O. Box 182615, Columbus, OH 43272-5046. (800) 262-4729. PRICE: $54.95;plus shipping and handling. ISBN: 0838586074. Summary: This textbook offers a practical and concise guide to the understanding, diagnosis, and treatment of urologic diseases. The text includes 47 chapters covering the anatomy of the genitourinary tract, embryology of the genitourinary system, symptoms of disorders of the genitourinary tract, physical examination of the genitourinary tract, urologic laboratory examination, radiology of the urinary tract, vascular interventional radiology, percutaneous endourology and ureterorenoscopy, laparoscopic surgery, radionuclide imaging, retrograde instrumentation of the urinary tract, urinary obstruction and stasis, vesicoureteral reflux (return of urine through the ureters to the kidney), bacterial infections, specific infections, sexually transmitted diseases, urinary stone (urolithiasis) disease, extracorporeal shock wave lithotripsy (ESWL, used to break up stones), injuries to the genitourinary tract, immunology and immunotherapy of urologic cancers, urothelial carcinoma (cancers of the bladder, ureter, and renal pelvis), renal parenchymal neoplasms (growths in the body of the kidney), neoplasms of the prostate gland, genital tumors, urinary diversion and bladder substitution, urologic laser surgery, chemotherapy of urologic tumors, radiotherapy of urologic tumors, neuropathic (arising from the nervous system) bladder disorders, urodynamic studies, urinary incontinence (involuntary loss of urine), disorders of the adrenal glands, disorders of the kidneys, diagnosis of medical renal diseases, oliguria (acute renal failure, lack of urination), chronic renal failure (CRF) and dialysis, renal transplantation, disorders of the ureter and ureteropelvic junction, disorders of the bladder and prostate (and seminal vesicles), disorders of the penis and male urethra, disorders of the female urethra, disorders of the testis and scrotum (and spermatic cord), skin diseases of the external genitalia, abnormalities of sexual determination and differentiation, renovascular hypertension, male infertility, and male sexual dysfunction. Each chapter concludes with references categorized by subject; the text concludes with an appendix of normal laboratory values and a subject index. The text features over 400 illustrations, including CT scans, radionuclide imaging scans, and x rays.
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Pathophysiologic Principles of Urology Source: Malden, MA: Blackwell Science. 1994. 528 p.
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Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. PRICE: $55.00. ISBN: 0865422214. Summary: This urology textbook emphasizes pathophysiologic concepts, correlates diagnostic testing with pathophysiology, and documents the scientific basis for the treatment of the common diseases of the genitourinary tract. Eighteen chapters cover topics including embryology; renal physiology; ureteral pathophysiology; bladder function; benign prostatic hyperplasia; male infertility; penile function; basic immunology; renal transplantation; urinary tract infection; antimicrobials in urology; calculi; renal and adrenal causes of hypertension; principles of radiation therapy; chemotherapy; flow cytometry in urologic oncology; urinary diversion; and lymphadenectomy in genitourinary cancers. Each chapter, written by experts in the field, includes tables and figures, as well as an annotated suggested reading list. A subject index concludes the book. •
Urology Annual: Volume 6 Source: Scranton, PA: W.W. Norton and Company. 1992. 377 p. Contact: Available from W.W. Norton and Company. National Book Company, 800 Keystone Industrial Park, Scranton, PA 18512-4601. (212) 354-5500; (800) 233-4830. PRICE: $85 (as of 1992). ISBN: 0393710122. Summary: This volume, the sixth in an annual series, offers comprehensive and timely presentations of various subjects that are of interest to practicing urologists. Sixteen articles cover topics including the pharmacologic management of benign prostatic hyperplasia (BPH); prostatic balloon dilatation and hyperthermia for BPH; the role of ultrasound in prostate cancer; prognostic factors in early prostate cancer; therapy for stage C cancer; the limits of resectability of prostate cancer; the management of metastatic prostate cancer; pitfalls in the management of testicular cancer patients and complications of therapy; biologic response modifiers in metastatic renal cell carcinoma; the indeterminate renal mass; new diagnostic modalities for impotence; male infertility; congenital genitourinary anomalies secondary to maternal drug use; renal changes in pregnancy; and the use of artificial intelligence in urologic decision making. A subject index is appended.
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 “male infertility” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “male infertility” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “male infertility” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Aspects of Male Infertility (International Perspectives in Urology, V. 4) by Ralph W. Devere White (Editor), Ralph D. White; ISBN: 0683024515; http://www.amazon.com/exec/obidos/ASIN/0683024515/icongroupinterna
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Atlas of Surgical Management of Male Infertility by Anthony J. Thomas, Harris M. Nagler; ISBN: 0896402827; http://www.amazon.com/exec/obidos/ASIN/0896402827/icongroupinterna
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Counselling in Male Infertility by Sammy Lee; ISBN: 063203906X; http://www.amazon.com/exec/obidos/ASIN/063203906X/icongroupinterna
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Diagnosing Male Infertility: New Possibilities and Limits (Progress in Reproductive Biology and Medicine, Vol. 15) by Giovanni M. Colpi (Editor); ISBN: 3805554435; http://www.amazon.com/exec/obidos/ASIN/3805554435/icongroupinterna
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Intracytoplasmic Sperm Injection: The Revolution in Male Infertility by Sean P. Flaherty (Editor), Colin D. Matthews (Editor); ISBN: 0643057633; http://www.amazon.com/exec/obidos/ASIN/0643057633/icongroupinterna
•
Male Infertility by T.B. Hargreave (Editor); ISBN: 0387198407; http://www.amazon.com/exec/obidos/ASIN/0387198407/icongroupinterna
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Male Infertility by Richard D. Amelar; ISBN: 0721612148; http://www.amazon.com/exec/obidos/ASIN/0721612148/icongroupinterna
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Male infertility : workup, treatment, and research : proceedings of the second Winfield W. Scott Symposium at the University of Rochester School of Medicine and Dentistry; ISBN: 0808909878; http://www.amazon.com/exec/obidos/ASIN/0808909878/icongroupinterna
•
Male Infertility and Sexual Dysfunction by Wayne J. G. Hellstrom (Editor); ISBN: 0387948597; http://www.amazon.com/exec/obidos/ASIN/0387948597/icongroupinterna
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Male Infertility from A to Z: A Concise Encyclopedia by J. M. G. Hollanders (Editor), et al; ISBN: 1850707588; http://www.amazon.com/exec/obidos/ASIN/1850707588/icongroupinterna
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Male Infertility: Clinical Investigation, Cause Evaluation and Treatment by F.H. Comhaire (Editor); ISBN: 0412572508; http://www.amazon.com/exec/obidos/ASIN/0412572508/icongroupinterna
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Male Infertility-Men Talking by Mary-Claire Mason; ISBN: 0415072905; http://www.amazon.com/exec/obidos/ASIN/0415072905/icongroupinterna
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Overcoming Male Infertility: Understanding Its Causes and Treatments by Leslie R. Schover (Author), Anthony J. Thomas (Author); ISBN: 0471244716; http://www.amazon.com/exec/obidos/ASIN/0471244716/icongroupinterna
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Surgery of Male Infertility by Marc Goldstein (Editor); ISBN: 0721666930; http://www.amazon.com/exec/obidos/ASIN/0721666930/icongroupinterna
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The Genetic Basis of Male Infertility (Results and Problems in Cell Differentiation, 28) by Ken McElreavey (Editor); ISBN: 3540662642; http://www.amazon.com/exec/obidos/ASIN/3540662642/icongroupinterna
•
Treating Male Infertility: New Possibilities (Progress in Reproductive Biology and Medicine; Vol. 16) by M. Balerna (Editor), Giovanni M. Colpi; ISBN: 3805558929; http://www.amazon.com/exec/obidos/ASIN/3805558929/icongroupinterna
•
Treatment of Male Infertility by J. Bain; ISBN: 0387109900; http://www.amazon.com/exec/obidos/ASIN/0387109900/icongroupinterna
•
Understanding Male Infertility: Basic and Clinical Approaches (Serono Symposia Publications from Raven Press, Vol. 98) by R.W. Whitcomb, B.R. Zirkin; ISBN:
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0881679143; http://www.amazon.com/exec/obidos/ASIN/0881679143/icongroupinterna •
Varicocele and Male Infertility II by M. Glezerman, E.W. Jecht (Editor); ISBN: 0387129855; http://www.amazon.com/exec/obidos/ASIN/0387129855/icongroupinterna
Chapters on Male Infertility In order to find chapters that specifically relate to male infertility, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and male infertility 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 “male infertility” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on male infertility: •
Disorders of Ejaculation Source: in Jequier, A.M. Male Infertility: A Guide for the Clinician. Malden, MA: Blackwell Science, Inc. 2000. p. 180-199. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $186.95. ISBN: 0632051299. Summary: Disorders of ejaculation are commonly found amongst the infertile male population, and it is important that the clinician understands the management of patients with these disorders. This chapter on disorders of ejaculation is from a textbook on male infertility. In this chapter, the author covers normal sexual response in the male, the anatomy of the posterior urethra, the mechanism of ejaculation, and disorders of ejaculation, including premature ejaculation, retarded ejaculation, retrograde ejaculation, ejaculatory failure, and painful ejaculation. Other topics include abnormalities that mimic retrograde ejaculation, examination of the postcoital urine specimen, methods of retrieving live sperm from men with retrograde ejaculation, surgery and patient selection for surgery, and drug therapy. The author concludes that disorders of ejaculation are a surprisingly common cause of infertility in men. Careful history taking is essential to provide an accurate diagnosis as many of the etiologies (causes) of these disorders may be relatively easy to treat. 4 figures. 1 table. 36 references.
•
Disorders of Erectile Function Source: in Jequier, A.M. Male Infertility: A Guide for the Clinician. Malden, MA: Blackwell Science, Inc. 2000. p. 200-225. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $186.95. ISBN: 0632051299.
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Summary: Disorders of erectile function are among the most common problems in men. This chapter on disorders of erectile function is from a textbook on male infertility. The author notes that the increase in the average age of patients requiring help with conception and the large numbers of men in second marriages who wish to start a second family raises the numbers of men with disorders of erection in an infertility clinic. The chapter begins with a review of the anatomy of the penis and the erectile tissue that is contained within it. Additional topics include the neuroendocrinology of erection, the mechanism of induction of erection, the etiology of erectile dysfunction (cavernosal smooth muscle dysfunction, arteriosclerosis, psychogenic impotence, endocrine causes, neurological impotence, prostatic surgery, drug effects, chronic illness, venogenic impotence, illicit drugs), the clinical evaluation of men with erectile failure, and treatment strategies, including psychosexual counseling, sildenafil (Viagra), mechanical devices (vacuum erection systems), intracavernosal injection therapy, topical and oral agents, penile prostheses, arterial surgery, and venous ligation. The cause of a patient's erectile failure can often be determined from a careful clinical history and clinical examination. As the treatment may depend for its success on an accurate clinical diagnosis, the clinical assessment of the patient with erectile failure is very important. 6 figures. 42 references. •
Spinal Cord Injury and Infertility Source: in Jequier, A.M. Male Infertility: A Guide for the Clinician. Malden, MA: Blackwell Science, Inc. 2000. p. 226-237. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $186.95. ISBN: 0632051299. Summary: There are many problems in spinal cord injury that will affect many systems in the body, but particularly severe is the effect that it has on the urological and reproductive tracts. This chapter on spinal cord injury and infertility is from a textbook on male infertility. Topics include the causation of the disorders in erection and ejaculation in men with spinal cord injury; damage to the autonomic nervous system in the absence of spinal cord injury; lumbar plexus neuropraxia; urological problems in spinal cord injury, including bladder atony, the reflex bladder, detrusor dyssynergia, urinary tract infection, calculi, prostatitis, and epididymitis; autonomic hyperreflexia; the management of the sexual dysfunction in men with spinal cord injury; management of ejaculatory failure in men with spinal injury; and assisted conception in the treatment of infertility in men with spinal injury. 1 figure. 18 references.
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CHAPTER
6.
PERIODICALS INFERTILITY
AND
NEWS
ON
MALE
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover male infertility.
News Services and Press Releases One of the simplest ways of tracking press releases on male infertility 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 “male infertility” (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 male infertility. 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 “male infertility” (or synonyms). The following was recently listed in this archive for male infertility: •
Male infertility can be passed on to children through assisted reproduction Source: Reuters Medical News Date: July 01, 2003
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•
Varicocele repair does not improve male infertility Source: Reuters Industry Breifing Date: May 29, 2003
•
Environmental estrogens may play role in male infertility without an obvious cause Source: Reuters Medical News Date: January 06, 2003
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Anastrozole treatment effective in treating some male infertility Source: Reuters Medical News Date: February 11, 2002
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Vasectomy now most common reason for US male infertility Source: Reuters Medical News Date: January 11, 2002
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Certain jobs may be linked to male infertility Source: Reuters Medical News Date: November 29, 2001
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Adeno-associated virus infection linked to male infertility Source: Reuters Industry Breifing Date: October 30, 2001
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Mitochondrial DNA polymerase gene mutations linked to male infertility Source: Reuters Medical News Date: October 24, 2001
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FDA clears Embryotech's screening test for male infertility Source: Reuters Medical News Date: October 02, 2001
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Male infertility linked to increased incidence of testicular cancer Source: Reuters Medical News Date: September 28, 2000
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Disposable diapers implicated in increase in male infertility Source: Reuters Medical News Date: September 25, 2000
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Serono gets FDA approval for Gonal-F to treat male, female infertility Source: Reuters Industry Breifing Date: June 06, 2000
•
Defective germ-line DNA repair may explain some male infertility Source: Reuters Medical News Date: June 05, 2000
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Seminal oxalic acid may play role in male infertility Source: Reuters Medical News Date: May 31, 2000
•
Defective Y-chromosome gene linked to male infertility Source: Reuters Medical News Date: December 01, 1999
•
Calcium channel blocker acts as male contraceptive; produces reversible male infertility Source: Reuters Medical News Date: September 30, 1999
Periodicals and News
•
Lifestyle Risks For Male Infertility Often Overlooked Source: Reuters Medical News Date: March 24, 1998
•
Intracytoplasmic Sperm Injection Linked To Transmission Of Genetic Causes Of Male Infertility Source: Reuters Medical News Date: August 15, 1997
•
Y-Chromosome Microdeletions: Role In Male Infertility Elucidated Source: Reuters Medical News Date: February 20, 1997
•
Urologists Often Treat Impotence, Incontinence But Not Male Infertility Source: Reuters Medical News Date: October 22, 1996
•
Anabolic Steroid Use Linked to Male Infertility Source: Reuters Medical News Date: July 12, 1996
•
Deficiency In Sperm Surface Protein Linked To Male Infertility Source: Reuters Medical News Date: June 06, 1996
•
New Treatment For Male Infertility Reported Source: Reuters Medical News Date: April 09, 1996
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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 “male infertility” (or synonyms) into the search box, and click on “Search News.” As this service is technology
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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 “male infertility” (or synonyms). If you know the name of a company that is relevant to male infertility, 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 “male infertility” (or synonyms).
Academic Periodicals covering Male Infertility Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to male infertility. In addition to these sources, you can search for articles covering male infertility 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 7. 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 male infertility. 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 male infertility. 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 male infertility: Choriogonadotropin Alfa •
Systemic - U.S. Brands: Ovidrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500249.html
Clomiphene •
Systemic - U.S. Brands: Clomid; Milophene; Serophene http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202151.html
Follitropin Alfa •
Systemic - U.S. Brands: Gonal-F http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203454.html
Follitropin Beta •
Systemic - U.S. Brands: Follistim http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203453.html
Ganirelix •
Systemic - U.S. Brands: Antagon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500052.html
Menotropins •
Systemic - U.S. Brands: Humegon; Pergonal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202347.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.
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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
141
APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “male infertility” (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 15014 357 891 6 90 16358
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “male infertility” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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 Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
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 Male Infertility In the following section, we will discuss databases and references which relate to the Genome Project and male infertility. 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).22 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. 19 Adapted 20
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. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 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 “male infertility” (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 male infertility: •
Male Infertility from Defect in Meiosis Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=309120 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
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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
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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
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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
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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
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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
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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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
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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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
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “male infertility” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 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 Database24 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. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “male infertility” (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).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 male infertility 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 male infertility. 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 male infertility. 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 “male infertility”:
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Guides on male infertility Infertility http://www.nlm.nih.gov/medlineplus/infertility.html
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Other guides Male Genital Disorders http://www.nlm.nih.gov/medlineplus/malegenitaldisorders.html Ovarian Cysts http://www.nlm.nih.gov/medlineplus/ovariancysts.html Reproductive Health http://www.nlm.nih.gov/medlineplus/reproductivehealth.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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “male infertility” (or synonyms). The following was recently posted: •
2002 guidelines for the management of pelvic infection and perihepatitis Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3043&nbr=2269&a mp;string=male+AND+infertility
•
AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2001 Mar-April; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2847&nbr=2073&a mp;string=male+AND+infertility
Patient Resources •
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American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 (revised 2002); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3525&nbr=2751&a mp;string=male+AND+infertility
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American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients-2002 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3524&nbr=2750&a mp;string=male+AND+infertility
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American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=male+AND+infertility
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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=male+AND+infertility
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Chlamydial urethritis and cervicitis Source: Finnish Medical Society Duodecim - Professional Association; 2001 June 5; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3401&nbr=2627&a mp;string=male+AND+infertility
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Diseases characterized by urethritis and cervicitis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3236&nbr=2462&a mp;string=male+AND+infertility
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Epididymitis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3239&nbr=2465&a mp;string=male+AND+infertility
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Evaluation of the newborn with developmental anomalies of the external genitalia Source: American Academy of Pediatrics - Medical Specialty Society; 2000 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2770&nbr=1996&a mp;string=male+AND+infertility
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Guidelines for detection of thyroid dysfunction Source: American Thyroid Association - Professional Association; 2000 June 12; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2361&nbr=1587&a mp;string=male+AND+infertility
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Pelvic inflammatory disease. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3238&nbr=2464&a mp;string=male+AND+infertility
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Report on evaluation of the azoospermic male Source: American Society for Reproductive Medicine - Private Nonprofit Organization; 2001 April; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2923&nbr=2149&a mp;string=male+AND+infertility
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Report on management of obstructive azoospermia Source: American Society for Reproductive Medicine - Private Nonprofit Organization; 2001 April; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2922&nbr=2148&a mp;string=male+AND+infertility
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Report on optimal evaluation of the infertile male Source: American Society for Reproductive Medicine - Private Nonprofit Organization; 2001 April; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2924&nbr=2150&a mp;string=male+AND+infertility
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Report on varicocele and infertility Source: American Society for Reproductive Medicine - Private Nonprofit Organization; 2001 April; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2921&nbr=2147&a mp;string=male+AND+infertility
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The management of infertility in tertiary care Source: Royal College of Obstetricians and Gynaecologists - Medical Specialty Society; 2000 January; 121 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2555&nbr=1781&a mp;string=male+AND+infertility
•
Ultrasonographic examinations: indications and preparation of the patient Source: Finnish Medical Society Duodecim - Professional Association; 2000 April 18 (revised 2001 October 24); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3385&nbr=2611&a mp;string=male+AND+infertility The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to male infertility. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to male infertility. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with male infertility. 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 male infertility. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “male infertility” (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 “male infertility”. 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 “male infertility” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 “male infertility” (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.25
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
25
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)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 159 •
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 161 •
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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MALE INFERTILITY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acrosin: A trypsin-like enzyme of spermatozoa which is not inhibited by alpha 1 antitrypsin. [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] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA
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and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] 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] Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte
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collagenase and elastase. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [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] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] 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]
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Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the 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] 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] Anginal: Pertaining to or characteristic of angina. [EU] 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] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] 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
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thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat 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] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be
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associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artificial Intelligence: The study and implementation of techniques and methods for designing computer systems to perform functions normally associated with human intelligence, such as understanding language, learning, reasoning, problem solving, etc. [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] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atony: Lack of normal tone or strength. [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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Azoospermia: Absence of spermatozoa in the semen, or failure of formation of spermatozoa. [EU]
Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls,
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multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Balloon Dilatation: Nonoperative repair of occluded vessels, ducts, or valves by insertion of a balloon catheter. It is used, amoung other things, to treat varices, torn retinas, renal and biliary calculi, gastric, bronchial and rectal stenoses, and heart valves, and includes catheterization with Fogarty and Foley catheters. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] 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]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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]
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Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [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] 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] 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 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 network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH]
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Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [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] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH]
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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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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] 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] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [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] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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]
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Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] 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]
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Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [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 Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chiasma: An anatomy term for an X-shaped crossing (for example, of nerves or tendons.) [NIH]
Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] 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]
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Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Deletion: Actual loss of a portion of the chromosome. [NIH] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Circumcision: Excision of the prepuce or part of it. [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] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [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] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior
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part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [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] Coitus: Sexual intercourse. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [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] 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] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] 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
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theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continence: The ability to hold in a bowel movement or urine. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive Agents: Chemical substances that prevent or reduce the probability of conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coreceptors: Invariant receptor of the helper T-cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH]
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Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryptorchidism: A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Cryptorchidism may increase the risk for development of testicular cancer. Also called undescended testicles. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytidine Triphosphate: Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH]
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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] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] Dermal: Pertaining to or coming from the skin. [NIH] DES: Diethylstilbestrol. 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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Dextrocardia: Location of the heart in the right hemithorax, with the apex directed to the right. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]
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Diagnostic trial: A research study that evaluates methods of detecting disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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] Digital rectal examination: DRE. An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the 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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Duct: A tube through which body fluids pass. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] 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] Ectopic: Pertaining to or characterized by ectopia. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]
Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH]
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Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine 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] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [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] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] 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.
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[NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epistasis: The degree of dominance exerted by one gene on the expression of a non-allelic gene. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting 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] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [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] 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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]
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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] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flagellum: A whiplike appendage of a cell. It can function either as an organ of locomotion or as a device for moving the fluid surrounding the cell. [NIH]
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Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Atresia: The degeneration and resorption of an ovarian follicle before it reaches maturity and ruptures. [NIH] Follicular Cyst: Cyst due to the occlusion of the duct of a follicle or small gland. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [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] Fungicide: An agent that destroys fungi. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamete Intrafallopian Transfer: A technique that came into use in the mid-1980's for assisted conception in infertile women with normal fallopian tubes. The protocol consists of hormonal stimulation of the ovaries, followed by laparoscopic follicular aspiration of oocytes, and then the transfer of sperm and oocytes by catheterization into the fallopian tubes. [NIH] Gametogenesis: The first phase of sexual reproduction which involves the transforming of certain cells in the parent into specialized reproductive cells. [NIH]
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Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] 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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] 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 Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying
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phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [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 Oxidase: An enzyme of the oxidoreductase class that catalyzes the conversion of beta-D-glucose and oxygen to D-glucono-1,5-lactone and peroxide. It is a flavoprotein, highly specific for beta-D-glucose. The enzyme is produced by Penicillium notatum and other fungi and has antibacterial activity in the presence of glucose and oxygen. It is used to estimate glucose concentration in blood or urine samples through the formation of colored dyes by the hydrogen peroxide produced in the reaction. (From Enzyme Nomenclature, 1992) EC 1.1.3.4. [NIH] Glucosylceramidase: A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in Gaucher's disease. EC 3.2.1.45. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions
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are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosyltransferases: Enzymes that catalyze the transfer of glycosyl groups to an acceptor. Most often another carbohydrate molecule acts as an acceptor, but inorganic phosphate can also act as an acceptor, such as in the case of phosphorylases. Some of the enzymes in this group also catalyze hydrolysis, which can be regarded as transfer of a glycosyl group from the donor to water. Subclasses include the hexosyltransferases, pentosyltransferases, sialyltransferases, and those transferring other glycosyl groups. EC 2.4. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] 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] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH]
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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] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] 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] Guanine: One of the four DNA bases. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [NIH] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] 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] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH]
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Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [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] 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] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]
Herniorrhaphy: An operation to repair a hernia. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [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]
Hexosyltransferases: Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-. [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] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [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] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless,
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odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [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] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [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] Hyperreflexia: Exaggeration of reflexes. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [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] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] 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] Ileus: Obstruction of the intestines. [EU]
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Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] Impregnation: 1. The act of fecundation or of rendering pregnant. 2. The process or act of saturation; a saturated condition. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within
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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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [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] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infertility, Male: Diminished or absent ability of the male to effect conception. [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] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH]
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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] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] 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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH]
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Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and
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increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] 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] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH]
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Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [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]
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] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to
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humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] 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]
Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [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] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU]
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Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [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] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] 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: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU]
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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] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Mesonephros: The excretory organ of the embryo, collective Wolffian tubules, which forms the urogenital fold from which the reproductive organs develop. The mesonephros is the permanent kidney in fish and amphibians, but atrophies in reptiles, birds, and mammals. [NIH]
Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Micromanipulation: The performance of dissections, injections, surgery, etc., by the use of micromanipulators (attachments to a microscope that manipulate tiny instruments). [NIH] Micromanipulators: A high precision instrument used in microinjection or chromosome dissection activities. [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]
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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] 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] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] 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] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief
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constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucociliary Clearance: Rate of ciliary and secretory activity of the respiratory submucosal glands. It is a non-specific host defense mechanism, measurable in vivo by mucus transfer, ciliary beat frequency, and clearance of radioactive tracers. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [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] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] 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]
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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] 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] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [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
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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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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]
Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [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]
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Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Orchitis: Inflammation of a testis. The disease is marked by pain, swelling, and a feeling of weight. It may occur idiopathically, or it may be associated with conditions such as mumps, gonorrhoea, filarial disease, syphilis, or tuberculosis. [EU] 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] Organic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form. [NIH] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [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 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] 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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [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] 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] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH]
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Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [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]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] 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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Palindrome: In genetic terms a DNA sequence which is the same (or very similar) when complementary strands are read in opposite directions. It has the property of rotational (dyad) symmetry. [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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] 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] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity.
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[NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] 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] 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 Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] 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] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Pentosyltransferases: Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another. (Dorland, 28th ed) EC 2.4.2. [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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] 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
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sensory receptors. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [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] 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] 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] 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] 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] 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]
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Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [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] 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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet 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] 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]
Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to
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accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. [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] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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
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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] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Prekallikrein: A plasma protein which is the precursor of kallikrein. Plasma that is deficient in prekallikrein has been found to be abnormal in thromboplastin formation, kinin generation, evolution of a permeability globulin, and plasmin formation. The absence of prekallikrein in plasma leads to Fletcher factor deficiency, a congenital disease. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [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] 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] 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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH]
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Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins B: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that
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forms part of semen. [NIH] Prostatic acid phosphatase: PAP. An enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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 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] 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] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] 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] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
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Psychosexual: Pertaining to the mental aspects of sex. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH]
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Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]
Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] 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] 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] 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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Reflex: An involuntary movement or exercise of function in a part, excited in response to a
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stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] 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] Rehabilitation Centers: Facilities which provide programs for rehabilitating the mentally or physically disabled individuals. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [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]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinas: A membrane at the back of the eye which is sensitive to light stimuli and composed of the photoreceptors proper, i. e. the cones and rods, and the nerve cells which transmit to the optic nerve the stimulation of the receptor elements. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It
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occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] 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]
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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] 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] Scrotum: In males, the external sac that contains the testicles. [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] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] 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] 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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal fluid: Fluid from the prostate and other sex glands that helps transport sperm out of the man's body during orgasm. Seminal fluid contains sugar as an energy source for sperm. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH]
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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] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Sialyltransferases: A group of enzymes with the general formula CMP-Nacetylneuraminate:acceptor N-acetylneuraminyl transferase. They catalyze the transfer of Nacetylneuraminic acid from CMP-N-acetylneuraminic acid to an acceptor, which is usually the terminal sugar residue of an oligosaccharide, a glycoprotein, or a glycolipid. EC 2.4.99.-. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet
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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] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [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] 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]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somites: Paired, segmented masses of mesodermal tissue that form along the length of the neural tube during the early stage of embryonic development. They give rise to the vertebral column and other tissues including voluntary muscle, bone, connective tissue, and the dermal layers of the skin. [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
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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] Sperm: The fecundating fluid of the male. [NIH] Sperm Capacitation: The process by which a spermatozoon becomes capable of fertilizing an ovum after it reaches the ampullary portion of the uterine tube. [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] Sperm Maturation: Posttesticular ripening of spermatozoa. [NIH] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Sperm Tail: The posterior, filiform part of spermatozoa, which provides sperm motility. [NIH]
Spermatic: A cord-like structure formed by the vas deferens and the blood vessels, nerves and lymphatics of the testis. [NIH] Spermatids: Male germ cells derived from spermatocytes and developing into spermatozoa. [NIH]
Spermatocyte: An early stage in the development of a spermatozoon. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatogonia: The spermatocytes. [NIH]
primitive
differentiated
male
gametes
which
give
rise
to
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] 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] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Squamous: Scaly, or platelike. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key
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signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [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] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Struvite: A type of kidney stone caused by infection. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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]
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Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superovulation: Occurrence or induction of release of more ova than are normally released at the same time in a given species. The term applies to both animals and humans. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptonemal Complex: The three-part structure of ribbon-like proteinaceous material that serves to align and join the paired homologous chromosomes during the pachytene stage of meiotic division. It is a prerequisite for crossing-over. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [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] Testicle: The male gonad where, in adult life, spermatozoa develop; the testis. [NIH]
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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] 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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermography: Measurement of the regional temperature of the body or an organ by infrared sensing devices, based on self-emanating infrared radiation. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] 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] 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
Dictionary 227
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] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] 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] Tonal: Based on special tests used for a topographic diagnosis of perceptive deafness (damage of the Corti organ, peripheral or central damage, i. e. the auditive cortex). [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH]
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Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor alpha: Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to epidermal growth factor and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown. [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]
Transforming Growth Factors: Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, transforming growth factor alpha and transforming growth factor beta. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triad: Trivalent. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trinucleotide Repeat Expansion: DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH]
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Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH]
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Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urethritis: Inflammation of the urethra. [EU] Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Calculi: Calculi in any part of the urinary tract. According to their composition or pattern of chemical composition distribution, urinary calculi types may include alternating or combination, cystine, decubitus, encysted, fibrin, hemp seed, matrix, mulberry, oxalate, struvite, urostealith, and xanthic calculi. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital Diseases: Diseases of the urogenital tract. [NIH] Urolithiasis: Stones in the urinary system. [NIH] Urologic Diseases: Diseases of the urinary tract in both male and female. It does not include the male genitalia for which urogenital diseases is used for general discussions of diseases of both the urinary tract and the genitalia. [NIH] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] 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] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [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] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Varicocele: A complex of dilated veins which surround the testicle, usually on the left side. [NIH]
Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH]
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Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]
Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] 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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [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] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [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] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH]
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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] Volition: Voluntary activity without external compulsion. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] 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] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]
233
INDEX A Abdomen, 165, 173, 180, 191, 198, 199, 208, 209, 219, 224, 226 Abdominal, 80, 165, 208, 219 Aberrant, 31, 165 Ablate, 44, 165 Abortion, 72, 165, 206, 213 Acceptor, 165, 190, 199, 208, 221 Acetylcholine, 165, 176, 205 Acetylcholinesterase, 113, 165 Acid Phosphatase, 165 Acidity, 165, 210 Acne, 165, 219 Acrosin, 111, 118, 165 Acrosome, 11, 30, 111, 118, 165 Acrosome Reaction, 11, 111, 118, 165 Acute renal, 124, 125, 165, 191 Adaptability, 165, 175 Adenine, 108, 165, 216 Adenosine, 53, 108, 121, 165, 210 Adenovirus, 21, 166 Adrenal Cortex, 166, 180, 185, 206, 213 Adrenal Glands, 125, 166 Adverse Effect, 6, 18, 166, 221 Aerobic, 166, 203 Aetiology, 64, 90, 166 Affinity, 42, 166, 199, 222 Agar, 166, 211 Agarose, 118, 166 Agonist, 19, 166, 182 Airway, 108, 166, 214 Algorithms, 124, 166, 172 Alimentary, 166, 196, 209 Alkaline, 89, 166, 174, 208 Alleles, 25, 166 Alpha Particles, 166, 216 Alpha-1, 166, 180 Alprostadil, 4, 167 Alternative medicine, 133, 167 Amino Acid Sequence, 113, 167, 168, 186, 188 Anaerobic, 167, 204 Anaesthesia, 167, 195 Anal, 16, 96, 167 Analgesic, 167, 184 Analog, 108, 167, 199 Anaphylatoxins, 167, 178 Anaplasia, 167
Anatomical, 167, 176, 194, 205, 220 Androgen-Binding Protein, 41, 167 Androgenic, 34, 112, 167 Androgens, 6, 9, 19, 40, 41, 49, 112, 117, 166, 167, 169 Anemia, 61, 147, 168, 173 Anesthesia, 166, 168, 184 Aneuploidy, 26, 168 Angina, 121, 168 Angina Pectoris, 121, 168 Anginal, 168, 205 Angiogenesis, 46, 168, 201 Angioplasty, 121, 168 Animal model, 12, 38, 54, 168 Anions, 168, 197, 221 Annealing, 168, 212 Anomalies, 72, 124, 126, 152, 168 Antiandrogens, 19, 168 Antibacterial, 168, 189, 223 Antibiotic, 92, 168, 223 Antibodies, 38, 48, 49, 113, 118, 168, 191, 194, 200, 211, 216 Antibody, 96, 106, 166, 168, 169, 178, 191, 192, 194, 195, 197, 201, 203, 216, 217, 223, 232 Anticoagulant, 168, 215 Antigen, 52, 117, 124, 166, 168, 169, 178, 192, 194, 195, 198, 201 Antigen-Antibody Complex, 169, 178 Anti-infective, 169, 193 Anti-inflammatory, 169, 189 Antioxidant, 75, 78, 169, 170, 208 Anus, 167, 169, 173, 178, 196, 217 Apoptosis, 19, 20, 25, 32, 34, 44, 52, 61, 119, 169, 175 Aqueous, 50, 109, 169, 171, 181, 193, 198 Arachidonic Acid, 169, 214 Arginine, 167, 169, 211, 229 Aromatase, 6, 55, 85, 169 Arterial, 129, 169, 170, 193, 215, 225 Arteries, 169, 170, 172, 179, 202, 204, 226 Arteriolar, 33, 169, 173 Arterioles, 169, 170, 172, 174, 202, 204 Arteriolosclerosis, 169, 170 Arteriosclerosis, 129, 170 Artery, 168, 169, 170, 172, 180, 183, 184, 216, 231 Artificial Intelligence, 126, 170
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Male Infertility
Ascorbic Acid, 97, 98, 170, 193, 208 Aseptic, 170, 224 Aspiration, 34, 62, 170, 187 Assay, 19, 62, 89, 104, 105, 106, 110, 120, 170 Asymptomatic, 170, 190, 208 Ataxia, 146, 147, 170, 226 Atony, 129, 170 Atrophy, 146, 170 Atypical, 16, 170 Autodigestion, 170, 208 Autonomic, 129, 165, 170, 205, 209, 222, 225 Autonomic Nervous System, 129, 170, 209, 222, 225 Azoospermia, 28, 32, 33, 52, 69, 99, 152, 170 B Bacteria, 168, 169, 170, 171, 183, 184, 186, 190, 202, 204, 206, 217, 223, 227, 230 Bacterial Infections, 125, 171 Bacteriophage, 171, 211, 227 Bacterium, 171, 191 Balloon Dilatation, 126, 171 Basal Ganglia, 170, 171 Basal Ganglia Diseases, 170, 171 Base, 16, 39, 165, 171, 180, 181, 188, 198, 211, 225, 229 Basement Membrane, 171, 186 Basophils, 171, 190, 199 Benign, 14, 49, 105, 124, 125, 126, 169, 171, 205, 217, 232 Benign prostatic hyperplasia, 14, 105, 124, 125, 126, 171 Bilateral, 21, 57, 73, 171 Bile, 171, 187, 199, 224 Biliary, 171, 174, 208 Biliary Tract, 171, 174, 208 Binding agent, 118, 171 Binding Sites, 24, 25, 171 Bioavailability, 113, 172 Bioavailable, 41, 172 Biochemical, 8, 9, 12, 22, 27, 30, 32, 35, 38, 42, 44, 47, 118, 166, 172, 187, 198, 221 Biogenesis, 7, 172 Biological response modifier, 172, 196 Biological therapy, 172, 191 Biomarkers, 33, 172 Biopsy, 15, 62, 92, 110, 172, 209 Biotechnology, 51, 52, 133, 143, 145, 146, 147, 172
Bladder, 4, 49, 89, 125, 126, 129, 171, 172, 180, 193, 195, 199, 214, 218, 228, 229, 230 Blastocyst, 172, 179, 183, 210 Blood Coagulation, 172, 174, 226 Blood Platelets, 172, 221, 226 Blood pressure, 172, 193, 203, 205, 222 Blood-Brain Barrier, 121, 172 Body Fluids, 172, 183, 222, 229 Bone Marrow, 173, 188, 194, 200, 203, 222, 224 Bone Morphogenetic Proteins, 8, 115, 173 Bone scan, 173, 219 Bowel, 167, 173, 179, 182, 224 Bowel Movement, 173, 179, 182, 224 Brachytherapy, 173, 196, 197, 216, 232 Bradykinin, 120, 121, 173, 197, 211 Branch, 161, 173, 181, 183, 209, 216, 222, 226 Breakdown, 42, 173, 182, 188 Breeding, 116, 173 Bronchi, 108, 173, 185, 227 Bronchial, 171, 173, 214 Bronchiectasis, 108, 173 Buccal, 18, 173 C Cadmium, 96, 99, 100, 173 Cadmium Poisoning, 173 Calcification, 170, 173 Calcium, 8, 33, 40, 42, 132, 173, 174, 178, 201, 205, 207, 221 Calculi, 126, 129, 171, 174, 230 Callus, 174, 184, 207 Calmodulin, 8, 34, 73, 174 Capillary, 173, 174 Capillary Permeability, 173, 174 Capsular, 123, 174 Carbohydrate, 174, 189, 190, 212 Carcinogenic, 174, 195, 213, 224 Carcinogens, 174, 206, 208 Carcinoma, 105, 124, 125, 174 Cardia, 109, 174 Cardiac, 174, 185, 204, 224 Cardiovascular, 174, 221, 222 Carnitine, 9, 25, 76, 98, 174 Carrier Proteins, 50, 174, 211 Case report, 57, 59, 66, 174 Caspase, 21, 175 Catheter, 171, 175, 184, 199 Catheterization, 168, 171, 175, 187 Cations, 175, 197 Caudal, 175, 193, 212 Cause of Death, 105, 175
Index 235
Cell Aggregation, 175, 207 Cell Count, 39, 60, 175 Cell Death, 20, 36, 44, 74, 119, 169, 175 Cell Differentiation, 14, 114, 127, 175, 221, 224 Cell Division, 28, 146, 171, 175, 181, 191, 196, 201, 202, 203, 211, 213, 220 Cell Lineage, 23, 31, 175 Cell membrane, 20, 174, 175, 176, 181, 197, 201, 210 Cell motility, 109, 175, 192 Cell proliferation, 23, 32, 114, 170, 175, 196, 221 Cell Respiration, 175, 203, 218 Cell Size, 175, 187 Cell Survival, 10, 20, 36, 50, 113, 175, 191 Cellulose, 175, 211 Central Nervous System, 113, 114, 116, 165, 170, 176, 183, 188, 189, 221 Centrosome, 11, 176, 203 Ceramide, 30, 176, 189 Cerebellar, 8, 170, 176, 217 Cerebellum, 176, 217 Cerebral, 170, 171, 172, 176, 185 Cerebral Cortex, 170, 176, 185 Cerebrum, 176, 229 Cervix, 165, 176, 218 Character, 168, 176, 181 Chemotactic Factors, 176, 178 Chemotherapy, 113, 125, 126, 151, 176 Chiasma, 78, 176, 180 Chin, 96, 176, 201 Chloride Channels, 114, 176 Cholera, 176, 221 Cholesterol, 21, 30, 171, 176, 201, 224 Choline, 165, 176 Chromatin, 27, 71, 110, 169, 176, 185, 205, 206 Chromosomal, 7, 26, 27, 36, 45, 59, 69, 84, 105, 168, 176, 219, 225 Chromosome Deletion, 36, 71, 82, 93, 105, 177 Chromosome Fragility, 177, 228 Chronic renal, 4, 125, 177, 212, 229 Ciliary, 23, 108, 177, 204 Circumcision, 124, 177 CIS, 36, 44, 177 C-kit receptor, 177, 223 Clear cell carcinoma, 177, 181 Climacteric, 121, 177 Clinical Medicine, 177, 213
Clinical trial, 5, 15, 99, 100, 143, 177, 179, 204, 209, 215, 217 Clone, 14, 26, 45, 177 Cloning, 28, 44, 172, 177, 196 Coagulation, 172, 177, 192, 198, 211, 226 Cochlea, 177, 195 Coenzyme, 170, 178, 198 Cofactor, 24, 27, 178, 215, 226 Coitus, 33, 178 Colchicine, 178, 229 Collagen, 167, 171, 178, 186, 188, 201, 211 Collapse, 173, 178 Colloidal, 178, 183, 221 Colon, 146, 178, 198 Complement, 38, 49, 61, 167, 178, 188, 200, 211 Computational Biology, 7, 143, 145, 178 Computed tomography, 179, 219 Computer Systems, 17, 170, 179 Conception, 21, 64, 88, 104, 129, 165, 179, 186, 187, 195, 213, 224 Concretion, 174, 179 Condoms, 26, 179 Conjugated, 179, 181, 219 Connective Tissue, 170, 173, 178, 179, 186, 188, 200, 202, 222 Constitutional, 36, 179 Consultation, 17, 124, 179 Consumption, 18, 179, 218 Contamination, 18, 179 Continence, 5, 179 Contraception, 12, 21, 28, 32, 38, 41, 58, 117, 121, 179 Contraceptive Agents, 40, 179 Contractility, 111, 179 Contraindications, ii, 179 Control group, 21, 179 Coordination, 8, 108, 176, 179 Coreceptors, 49, 179 Coronary, 121, 168, 179, 180, 202, 204 Coronary Arteriosclerosis, 179, 204 Coronary Circulation, 168, 180 Coronary Thrombosis, 180, 202, 204 Corpus, 180, 209, 213 Cortex, 180, 217, 227 Corticosteroids, 180, 189 Cortisol, 6, 180 Cost Savings, 100, 180 Creatine, 60, 180 Creatine Kinase, 60, 180 Creatinine, 180, 229 Criterion, 88, 180
236
Male Infertility
Crossing-over, 180, 217, 225 Cryptorchidism, 4, 8, 57, 65, 124, 180 Curative, 180, 205, 226 Cyclic, 36, 174, 180, 214 Cyclodextrins, 21, 180 Cyst, 46, 180, 187 Cystine, 180, 230 Cystitis, 124, 125, 180 Cytidine, 108, 180 Cytidine Triphosphate, 108, 180 Cytochrome, 6, 169, 181 Cytogenetics, 36, 181 Cytokine, 31, 48, 181 Cytoplasm, 169, 171, 175, 181, 185, 190, 203, 205, 219, 230 Cytosine, 180, 181, 216 Cytotoxic, 181, 194, 216, 217, 221 D Decision Making, 126, 181 Decubitus, 181, 230 Degenerative, 181, 192 Deletion, 7, 12, 26, 37, 44, 50, 53, 61, 105, 169, 181 Denaturation, 181, 212 Density, 11, 18, 110, 181, 187, 206, 212 Depolarization, 181, 221 Dermal, 181, 222 DES, 12, 167, 181 Deuterium, 181, 193 Developmental Biology, 24, 31, 41, 49, 181 Dextrocardia, 109, 181 Diagnostic procedure, 103, 134, 181 Diagnostic trial, 67, 182 Diastolic, 182, 193 Digestion, 104, 166, 171, 173, 182, 199, 224 Digestive system, 101, 182 Digital rectal examination, 4, 182 Dihydrotestosterone, 182, 217 Dihydroxy, 111, 182 Dilatation, 3, 165, 168, 173, 182, 213 Dilation, 173, 182 Diploid, 28, 119, 168, 182, 203, 211, 229 Direct, iii, 6, 11, 18, 33, 34, 46, 105, 106, 108, 135, 177, 182, 217 Dissection, 84, 182, 200, 202 Dissociation, 166, 182, 197 Distal, 9, 32, 43, 50, 182, 215 Dominance, 182, 185 Dopamine, 182, 205, 210 Dorsal, 182, 212 Drive, ii, vi, 24, 41, 95, 123, 124, 182, 197, 199
Drug Interactions, 136, 182 Duct, 32, 43, 50, 62, 175, 183, 187, 219, 224, 230 Dyes, 118, 171, 183, 187, 189, 205 Dynein, 6, 22, 183 Dyskinesia, 23, 108, 183 Dysplasia, 147, 183 Dystrophy, 146, 183 E Ectopic, 15, 31, 44, 47, 50, 183 Ectopic Pregnancy, 15, 31, 183 Effector, 165, 178, 183 Efferent, 6, 167, 183 Efficacy, 38, 183 Ejaculation, 32, 50, 55, 128, 129, 183, 220 Elasticity, 170, 179, 183 Elective, 183 Electrolyte, 108, 183, 212, 222, 229 Electrophoresis, 12, 89, 183 Electrophysiological, 32, 183 Elementary Particles, 183, 200, 205, 215 Embolus, 183, 195 Embryo, 27, 94, 165, 172, 175, 183, 184, 195, 202, 206, 213, 223 Embryo Transfer, 183, 213 Embryogenesis, 51, 184, 223 Embryology, 125, 126, 184 Endarterectomy, 168, 184 Endocrine System, 184, 205 Endocrinology, 15, 24, 53, 58, 59, 64, 69, 78, 85, 184, 191 Endogenous, 27, 36, 44, 111, 182, 184, 208, 215, 227 Endometrial, 15, 31, 110, 184 Endometriosis, 14, 184 Endometrium, 31, 184, 201 Endorphin, 56, 184 Endothelial cell, 46, 172, 184, 226 Endotoxic, 184, 199 Endotoxin, 184, 229 End-stage renal, 4, 177, 184, 212 Enhancer, 184, 218 Enkephalins, 184, 205 Enuresis, 124, 184 Environmental Exposure, 96, 99, 184, 206 Environmental Health, 77, 99, 100, 142, 144, 184 Enzymatic, 24, 28, 167, 174, 178, 185, 201, 212 Eosinophils, 185, 190, 199 Epidemiological, 18, 80, 185 Epidermal, 111, 185, 201, 228, 232
Index 237
Epidermis, 185 Epinephrine, 182, 185, 205, 229 Epistasis, 22, 185 Epithelial, 14, 23, 27, 32, 50, 105, 108, 185, 190, 192 Epithelial Cells, 23, 108, 185, 192 Epithelium, 8, 25, 32, 43, 50, 171, 185, 208, 228 Erectile, 4, 92, 124, 125, 128, 129, 185, 209 Erection, 129, 185 Erythrocytes, 168, 173, 185, 217 Esophagus, 182, 185, 210, 218, 224, 230 Essential Tremor, 146, 185 Estradiol, 6, 33, 40, 185 Estrogen, 6, 33, 169, 185 Estrogen receptor, 33, 185 Eukaryotic Cells, 185, 195, 206, 207, 229 Evoke, 114, 185, 224 Excitation, 185, 187, 205 Exogenous, 184, 185, 188, 215 Exon, 12, 85, 186 External-beam radiation, 186, 197, 216, 232 Extracellular, 104, 115, 179, 186, 201, 222 Extracellular Matrix, 104, 179, 186, 201 Extracellular Matrix Proteins, 186, 201 Extracellular Space, 186 Extracorporeal, 125, 186 Extraction, 36, 186 Eye Infections, 166, 186 F Fallopian tube, 186, 187, 218 Family Planning, 30, 83, 143, 186 Fat, 169, 173, 176, 183, 186, 199, 212 Fatigue, 186, 191 Fatty acids, 9, 111, 186, 190, 214, 226 Febrile, 186, 223 Fertilization in Vitro, 186, 213 Fetus, 165, 186, 187, 210, 213, 223, 224, 230 Fibrin, 172, 186, 226, 230 Fibrosis, 68, 84, 114, 147, 186, 220 Flagellum, 6, 22, 24, 37, 186 Flow Cytometry, 23, 61, 120, 126, 187 Fluorescence, 17, 54, 187 Fluorescent Dyes, 187 Foetoplacental, 187, 206 Fold, 34, 187, 202, 213 Follicles, 23, 187, 195 Follicular Atresia, 13, 187 Follicular Cyst, 13, 187 Fractionation, 42, 187 Free Radicals, 169, 182, 187
Fructose, 112, 187 Fungi, 186, 187, 189, 202, 232 Fungicide, 19, 187 G Gallbladder, 165, 171, 182, 187, 199 Gamete Intrafallopian Transfer, 77, 187 Gametogenesis, 51, 187 Gamma Rays, 188, 216, 217 Ganglia, 165, 171, 188, 205, 209, 225 Gangrenous, 188, 221 Gas, 188, 193, 205, 218 Gastric, 170, 171, 174, 188 Gastrin, 188, 192 Gastrointestinal, 173, 185, 188, 221, 222, 224, 229 Gastrointestinal tract, 188, 221, 229 Gelatin, 188, 190, 225, 226 Gene Expression, 14, 23, 31, 33, 34, 36, 40, 41, 42, 44, 50, 53, 100, 147, 188 Gene Targeting, 28, 188 Gene Therapy, 44, 166, 188 Genetic Code, 188, 206 Genetic Counseling, 68, 188 Genetic Engineering, 172, 177, 188 Genetic Screening, 60, 188 Genetic testing, 68, 116, 189, 212 Genetics, 9, 22, 27, 33, 37, 44, 61, 63, 66, 69, 71, 72, 75, 76, 78, 85, 89, 116, 181, 182, 189 Genital, 6, 19, 32, 99, 117, 124, 125, 150, 177, 189, 191, 230 Genitourinary, 49, 123, 125, 126, 150, 189, 230 Genitourinary system, 123, 125, 189 Genomics, 26, 42, 69, 189 Genotype, 7, 189, 210 Gestation, 189, 209, 210, 223 Gland, 13, 52, 62, 82, 109, 166, 187, 189, 200, 201, 208, 210, 214, 220, 224, 226, 227 Glomerular, 189, 218 Glucans, 180, 189 Glucocorticoid, 6, 189 Glucose, 19, 146, 170, 175, 180, 189, 190, 191, 195, 196, 219 Glucose Oxidase, 19, 189 Glucosylceramidase, 30, 189 Glutamic Acid, 189, 205 Glycerol, 189, 190, 210 Glycerophospholipids, 189, 210 Glycine, 167, 190, 205, 221 Glycolysis, 24, 190 Glycoprotein, 104, 190, 221, 226, 229
238
Male Infertility
Glycosyltransferases, 39, 190 Goblet Cells, 108, 190 Gonad, 28, 31, 190, 225 Gonadal, 6, 12, 31, 106, 112, 190, 224 Gonadorelin, 190, 199 Gonadotropin, 6, 21, 40, 41, 190, 199 Gonorrhoea, 190, 207 Governing Board, 190, 213 Graft, 190, 192, 194 Graft Rejection, 190, 194 Grafting, 190, 194 Gram-negative, 184, 190, 204 Granulocytes, 190, 221, 232 Granuloma, 8, 190 Granulosa Cells, 191, 195 Gravidity, 64, 191 Groin, 112, 191, 195 Growth factors, 10, 20, 31, 113, 191 Guanine, 35, 191, 216 Gynecology, 12, 14, 15, 21, 30, 31, 37, 50, 60, 63, 64, 65, 67, 69, 70, 80, 87, 96, 191 H Haemorrhage, 165, 191 Haploid, 28, 42, 119, 191, 211 Haplotypes, 26, 191 Haptens, 166, 191 Heart failure, 121, 191 Hematuria, 124, 191 Heme, 181, 191 Hemoglobin, 168, 185, 191 Hemoglobinopathies, 188, 191 Hemoglobinuria, 146, 191 Hemolytic, 61, 191 Hemorrhage, 192, 224 Hemostasis, 192, 221 Hepatic, 192, 199 Hepatitis, 121, 192 Hepatocyte, 10, 192 Hepatocyte Growth Factor, 10, 192 Hereditary, 192, 219 Heredity, 188, 189, 192 Hernia, 192 Herniorrhaphy, 89, 192 Heterodimer, 173, 192 Heterogeneity, 166, 192 Hexosyltransferases, 190, 192 Histology, 3, 13, 23, 34, 60, 192 Homeostasis, 20, 50, 192, 222 Homologous, 12, 39, 44, 106, 115, 166, 180, 188, 192, 220, 225 Hormonal, 4, 6, 26, 33, 70, 71, 112, 117, 170, 187, 192
Hormone, 12, 13, 18, 23, 33, 34, 66, 109, 167, 180, 181, 185, 188, 190, 192, 195, 196, 199, 213, 221, 226, 227, 228 Host, 115, 121, 171, 192, 194, 204, 219 Human Genome Project, 26, 148, 192 Human papillomavirus, 105, 192 Hybrid, 7, 12, 22, 24, 25, 35, 38, 42, 44, 177, 192 Hybridization, 23, 192 Hydrogen, 19, 165, 171, 174, 181, 186, 189, 192, 193, 199, 203, 205, 206, 207, 208, 210, 215 Hydrogen Peroxide, 19, 189, 193, 199 Hydrolysis, 114, 165, 190, 193, 197, 210, 215, 229 Hydronephrosis, 124, 193 Hydrophobic, 50, 189, 193 Hydroxyproline, 167, 178, 193 Hyperplasia, 6, 13, 193 Hyperreflexia, 129, 193 Hypertension, 121, 125, 126, 170, 193, 227, 229 Hyperthermia, 126, 193 Hyperthyroidism, 151, 193 Hypertrophy, 124, 171, 193 Hypogonadism, 34, 54, 151, 193 Hypotensive, 193, 197 Hypothalamic, 6, 40, 193 Hypothalamus, 170, 190, 193, 210 Hypothyroidism, 151, 193 I Id, 97, 146, 150, 151, 152, 153, 160, 162, 193 Idiopathic, 11, 32, 34, 35, 36, 51, 54, 69, 73, 74, 76, 78, 81, 85, 96, 109, 193 Ileus, 121, 193 Immortal, 48, 194 Immune function, 194, 228 Immune response, 8, 169, 190, 191, 194, 200, 224, 229, 231 Immune Sera, 194 Immune system, 31, 109, 172, 194, 200, 204, 210, 230, 232 Immunization, 117, 194 Immunodeficiency, 146, 194 Immunogenic, 194, 199 Immunoglobulin, 55, 168, 194, 203 Immunologic, 176, 194, 217 Immunology, 27, 49, 125, 126, 166, 187, 194 Immunosuppressive, 4, 189, 194 Immunosuppressive Agents, 4, 194 Immunosuppressive therapy, 194
Index 239
Immunotherapy, 125, 172, 194 Impairment, 41, 108, 109, 170, 183, 186, 194, 202 Implant radiation, 194, 196, 197, 216, 232 Implantation, 31, 38, 179, 194, 206 Impotence, 4, 73, 78, 124, 126, 129, 133, 185, 194 Impregnation, 116, 194 In situ, 9, 29, 34, 36, 37, 41, 194 In Situ Hybridization, 9, 31, 36, 37, 41, 194 In vivo, 20, 23, 27, 28, 31, 35, 39, 43, 50, 104, 106, 113, 115, 117, 188, 195, 204, 208, 226 Incision, 195, 197 Incontinence, 49, 124, 125, 133, 195 Indicative, 105, 126, 195, 209, 231 Induction, 31, 34, 129, 167, 195, 225 Infarction, 121, 195 Infertility, Male, 114, 195 Ingestion, 173, 195 Inguinal, 89, 195 Inhibin, 18, 40, 195 Initiation, 6, 20, 24, 44, 195, 213, 227 Inlay, 195, 218 Inner ear, 108, 195 Inorganic, 190, 195, 204 Inositol, 25, 195 Insecticides, 196, 210 Insertional, 23, 196 Insight, 10, 13, 14, 39, 41, 46, 196 Instillation, 108, 196 Insulin, 7, 48, 196 Insulin-dependent diabetes mellitus, 196 Insulin-like, 7, 196 Interferon, 58, 87, 196 Interferon-alpha, 196 Interleukins, 194, 196 Intermittent, 196, 200 Internal Medicine, 9, 49, 184, 196 Internal radiation, 196, 197, 216, 232 Interphase, 38, 176, 196, 206 Interstitial, 109, 124, 125, 173, 186, 196, 197, 201, 218, 232 Intestinal, 196, 200 Intestines, 165, 188, 193, 196, 220 Intoxication, 196, 232 Intracellular, 25, 32, 42, 113, 195, 196, 201, 212, 214, 217, 221 Intracellular Membranes, 196, 201 Intramuscular, 109, 197, 209 Intramuscular injection, 109, 197 Intravenous, 197, 209
Intrinsic, 166, 171, 197 Invasive, 4, 110, 197, 200 Invertebrates, 115, 116, 197 Involuntary, 110, 125, 171, 184, 185, 197, 204, 217 Ion Channels, 40, 197 Ion Transport, 32, 197 Ionization, 12, 197 Ionizing, 166, 184, 197, 217 Ions, 25, 114, 165, 171, 174, 176, 182, 183, 193, 197 Irradiation, 113, 197, 232 Ischemia, 170, 197 Isoenzyme, 180, 197 K Kallidin, 121, 173, 197 Kallikreins, 197 Kb, 39, 50, 142, 198 Keto, 111, 198 Kidney Disease, 101, 142, 147, 193, 198 Kidney Failure, 184, 198 Kidney Pelvis, 198, 229 Kidney stone, 193, 198, 207, 224 L Labile, 50, 178, 198 Labyrinth, 178, 195, 198, 220, 231 Lactate Dehydrogenase, 44, 198 Lactation, 198, 206 Laparoscopy, 110, 198 Large Intestine, 182, 196, 198, 217, 222 Larynx, 198, 227 Laser Surgery, 125, 198 Latent, 31, 105, 107, 198 Lectin, 72, 198 Lens, 174, 198 Lethal, 12, 199 Lethargy, 193, 199 Leukemia, 146, 188, 199 Leukocytes, 19, 171, 173, 176, 185, 190, 196, 199, 203, 205, 229 Leuprolide, 21, 199 Libido, 167, 199 Library Services, 160, 199 Ligament, 186, 199, 214 Ligands, 49, 199 Ligation, 77, 129, 199 Linkage, 17, 78, 199 Lipid, 18, 30, 60, 78, 170, 174, 176, 189, 196, 198, 199, 208 Lipid A, 30, 199 Lipid Peroxidation, 18, 199, 208 Lipophilic, 199, 211
240
Male Infertility
Lipopolysaccharides, 199 Lithotripsy, 125, 199 Liver, 9, 121, 165, 169, 171, 174, 182, 187, 192, 199, 219 Liver Cirrhosis, 121, 199 Liver scan, 199, 219 Localization, 12, 20, 24, 28, 30, 35, 41, 73, 121, 199 Localized, 40, 50, 106, 107, 195, 199, 211 Locomotion, 186, 199, 211 Long-Term Care, 5, 200 Loop, 23, 192, 200 Lumbar, 129, 200 Lumen, 32, 43, 50, 200 Lymph, 184, 200 Lymph node, 200 Lymphadenectomy, 126, 200 Lymphatic, 195, 200, 202, 211, 222, 226 Lymphocyte, 169, 200, 201 Lymphoid, 168, 180, 200 Lymphoma, 146, 200 M Magnetic Resonance Imaging, 200, 219 Magnetic Resonance Spectroscopy, 4, 200 Major Histocompatibility Complex, 191, 200 Malabsorption, 146, 200 Malignancy, 200, 208 Malignant, 104, 105, 125, 146, 170, 200, 205, 217 Malnutrition, 170, 200, 204 Mammary, 52, 82, 200, 201 Manifest, 6, 200 Mastitis, 201, 221 Matrilysin, 52, 82, 201 Matrix metalloproteinase, 82, 201 Medial, 170, 201 Mediate, 12, 40, 182, 201 Mediator, 201, 221 MEDLINE, 143, 145, 147, 201 Meiosis, 31, 45, 52, 71, 146, 201, 225 Melanin, 201, 210, 229 Melanocytes, 201 Melanoma, 146, 201 Membrane Fusion, 11, 201 Membrane Glycoproteins, 201 Membrane Lipids, 201, 210 Meninges, 176, 201 Menopause, 124, 201, 206 Menstrual Cycle, 201, 206, 213 Menstruation, 201
Mental, iv, 5, 101, 142, 144, 148, 176, 182, 186, 193, 201, 202, 215, 216, 219, 220, 229 Mental Disorders, 101, 202, 215 Mental Health, iv, 5, 101, 142, 144, 202, 216 Mercury, 187, 202 Mesenchymal, 112, 202 Mesoderm, 26, 115, 202 Mesonephros, 10, 46, 202 Metabolic disorder, 124, 202 Metabolite, 19, 202 Metaphase, 38, 80, 202 Metaplasia, 50, 202 Metastasis, 105, 201, 202 Metastatic, 105, 126, 202, 220 MI, 104, 111, 116, 163, 202 Microbiology, 170, 202 Microcirculation, 199, 202 Micromanipulation, 36, 64, 202 Micromanipulators, 202 Microorganism, 178, 202, 209, 232 Microscopy, 7, 17, 23, 35, 110, 118, 171, 202, 206 Migration, 26, 28, 46, 203 Milliliter, 203, 223 Miscarriage, 31, 203 Mitochondria, 19, 203, 207 Mitosis, 169, 176, 203 Mitotic, 176, 203, 231 Mitotic Spindle Apparatus, 176, 203 Modeling, 24, 203 Modification, 28, 167, 188, 203, 216 Monitor, 24, 118, 180, 203, 206 Monoclonal, 197, 203, 216, 232 Monocytes, 199, 203 Mononuclear, 190, 203, 229 Monosomy, 168, 203 Morphogenesis, 10, 46, 203 Morphological, 6, 10, 41, 44, 46, 47, 106, 118, 119, 183, 201, 203 Morphology, 6, 11, 12, 13, 29, 84, 87, 88, 106, 110, 120, 203 Motility, 7, 11, 12, 18, 24, 30, 38, 40, 106, 108, 110, 113, 120, 203, 221 Mucins, 108, 190, 203 Mucociliary, 108, 204, 222 Mucociliary Clearance, 108, 204 Mucus, 108, 204 Multicenter study, 76, 204 Muscle Fibers, 204 Muscular Atrophy, 146, 204 Muscular Dystrophies, 183, 204
Index 241
Mycoplasma, 89, 204 Myocardial infarction, 121, 180, 202, 204 Myocardial Ischemia, 121, 168, 204 Myocardium, 168, 202, 204 Myotonic Dystrophy, 146, 204, 228 N Naive, 8, 204 Natural selection, 172, 204 NCI, 1, 100, 141, 177, 204 Need, 3, 25, 30, 108, 112, 123, 128, 154, 166, 177, 201, 204, 228 Neoplasia, 146, 205 Neoplasm, 205, 229 Neoplastic, 167, 200, 205, 228 Nephropathy, 198, 205 Nerve, 168, 170, 176, 183, 201, 205, 212, 218, 220, 224, 227, 228 Nervous System, 113, 125, 146, 170, 176, 201, 205, 209, 225 Networks, 23, 205 Neural, 37, 113, 205, 222 Neuroendocrinology, 129, 205 Neuromuscular, 165, 205, 229 Neuromuscular Junction, 165, 205 Neuronal, 10, 205 Neurons, 188, 205, 225 Neurotransmitter, 32, 165, 166, 167, 173, 182, 189, 190, 197, 205, 221, 224 Neutrons, 166, 197, 205, 216 Neutrophils, 108, 109, 190, 199, 205 Niacin, 205, 229 Nifedipine, 59, 205 Nitrogen, 166, 167, 186, 205, 207, 229 Norepinephrine, 182, 205 Nuclear, 18, 29, 68, 106, 110, 119, 122, 171, 185, 188, 206 Nuclear Matrix, 68, 206 Nuclear Pore, 206 Nucleates, 176, 206 Nuclei, 11, 29, 166, 188, 200, 203, 205, 206, 215 Nucleic acid, 115, 117, 121, 181, 188, 192, 194, 205, 206, 216 Nucleic Acid Hybridization, 192, 206 Nucleolus, 206, 219 O Oestrogen, 55, 206 Oliguria, 125, 198, 206 Oncogene, 105, 146, 192, 206, 223 Oncology, 4, 33, 39, 56, 125, 126, 151, 206 Oocytes, 11, 28, 74, 80, 90, 118, 187, 206 Opacity, 181, 206
Operon, 207, 213, 218 Orchitis, 66, 207 Organelles, 51, 181, 201, 203, 207, 211 Organic Chemicals, 19, 207 Organogenesis, 116, 207 Orgasm, 183, 207, 220 Osmolality, 25, 207 Osmoles, 207 Osmosis, 207 Osmotic, 25, 207, 221 Osteoporosis, 206, 207 Otitis, 108, 207 Otitis Media, 108, 207 Ovarian Follicle, 31, 187, 191, 207 Ovaries, 169, 187, 207, 218, 221 Ovary, 9, 13, 31, 46, 185, 190, 206, 207 Ovulation, 8, 191, 207 Ovum, 165, 189, 207, 209, 213, 223, 232 Oxalate, 207, 230 Oxalic Acid, 132, 208 Oxidants, 75, 86, 208 Oxidation, 9, 21, 165, 169, 180, 181, 199, 208 Oxidation-Reduction, 208 Oxidative Stress, 18, 208 Oxides, 111, 208 P Palindrome, 44, 45, 208 Palliative, 206, 208, 226 Pancreas, 165, 172, 182, 196, 208, 229 Pancreatic, 146, 174, 208 Pancreatic cancer, 146, 208 Pancreatitis, 16, 114, 121, 208 Papillomavirus, 105, 208 Paranasal Sinuses, 208, 222 Parasite, 209 Parasitic, 91, 209 Parenteral, 112, 209 Paroxysmal, 146, 168, 209 Pathogen, 22, 209 Pathogenesis, 16, 20, 31, 49, 52, 60, 61, 72, 83, 209 Pathologic, 169, 172, 179, 209, 215, 218 Pathologic Processes, 169, 209 Pathologies, 19, 209 Pathophysiology, 3, 13, 37, 49, 59, 83, 126, 209 Patient Selection, 128, 209 Pellucida, 104, 106, 209 Pelvic, 150, 152, 184, 209, 214 Pelvis, 165, 200, 207, 209, 230 Penis, 125, 129, 179, 183, 209, 213, 218
242
Male Infertility
Pentosyltransferases, 190, 209 Peptide, 7, 42, 113, 167, 209, 215, 227 Percutaneous, 34, 121, 125, 199, 209 Perinatal, 124, 209 Peripheral blood, 167, 196, 209 Peripheral Nervous System, 184, 205, 209, 224 Peroxide, 189, 210 Pesticides, 18, 196, 210 PH, 47, 69, 71, 117, 124, 126, 210 Phagocyte, 208, 210 Pharmacologic, 126, 168, 210, 227 Pharynx, 108, 210 Phenotype, 7, 12, 13, 28, 38, 51, 117, 210, 228 Phenyl, 111, 210 Phenylalanine, 210, 229 Phospholipases, 210, 221 Phospholipids, 92, 186, 195, 201, 210 Phosphorus, 174, 207, 210 Phosphorylated, 23, 114, 178, 210 Phosphorylation, 21, 23, 24, 54, 114, 210 Physical Examination, 7, 124, 125, 210 Physiologic, 29, 31, 166, 177, 201, 210, 214, 217, 218 Physiology, 9, 13, 27, 32, 47, 108, 111, 124, 126, 183, 184, 191, 210 Pituitary Gland, 109, 190, 210 Placenta, 169, 185, 187, 210, 213 Plants, 35, 173, 176, 189, 198, 203, 206, 208, 211, 219, 227 Plaque, 168, 211 Plasma cells, 168, 211 Plasma Kallikrein, 121, 198, 211 Plasma protein, 211, 213, 221 Plasminogen, 211 Plastids, 207, 211 Platelet Activation, 61, 211, 222 Platelet Aggregation, 167, 211, 214, 226 Platelets, 211, 226 Platinum, 200, 211 Plexus, 129, 211 Pneumonia, 179, 211 Point Mutation, 29, 211 Polychlorinated Biphenyls, 18, 211 Polycystic, 6, 14, 147, 212 Polyethylene, 212, 225 Polyethylene Glycols, 212, 225 Polymerase, 52, 72, 105, 122, 132, 212, 213, 218 Polymerase Chain Reaction, 105, 212 Polymorphism, 63, 212
Polysaccharide, 166, 169, 175, 212 Posterior, 115, 128, 167, 170, 176, 182, 208, 212, 223 Postnatal, 9, 10, 23, 124, 212, 224 Postsynaptic, 212, 221 Post-translational, 167, 212 Potassium, 33, 212 Potentiation, 212, 221 Practice Guidelines, 144, 150, 212 Precipitation, 42, 213 Precursor, 8, 10, 46, 169, 173, 176, 182, 183, 185, 205, 210, 211, 213, 228, 229 Pregnancy Outcome, 31, 213 Prekallikrein, 211, 213 Prenatal, 183, 189, 213 Prepuce, 177, 213 Presynaptic, 205, 213 Prevalence, 70, 213 Probe, 34, 40, 50, 104, 213 Problem Solving, 170, 213 Progeny, 9, 47, 213 Progesterone, 213, 224 Prognostic factor, 87, 126, 213 Progression, 28, 32, 38, 120, 168, 201, 213 Progressive, 41, 61, 109, 110, 169, 175, 177, 191, 204, 211, 213, 218, 229 Promoter, 12, 14, 23, 25, 36, 39, 44, 45, 50, 213 Promotor, 213, 218 Prophase, 44, 206, 213, 225 Prophylaxis, 213, 219 Proportional, 207, 214 Prostaglandin, 111, 214, 226 Prostaglandin Endoperoxides, 214, 226 Prostaglandins A, 111, 214 Prostaglandins B, 111, 214 Prostaglandins D, 214 Prostaglandins F, 214 Prostaglandins H, 111, 214 Prostate, 4, 5, 13, 19, 43, 49, 105, 124, 125, 126, 146, 171, 172, 198, 206, 214, 215, 218, 220, 229 Prostate gland, 125, 214, 215 Prostatic acid phosphatase, 75, 215 Prostatic Hyperplasia, 49, 215 Prostatitis, 84, 129, 215 Protease, 36, 44, 215 Protein Binding, 35, 44, 215 Protein C, 11, 23, 24, 30, 121, 122, 167, 171, 215 Protein Conformation, 167, 215 Protein S, 19, 43, 147, 172, 188, 215, 219
Index 243
Proteolytic, 121, 166, 173, 178, 197, 215 Proteome, 12, 215 Protocol, 15, 16, 187, 215 Protons, 166, 193, 197, 200, 215, 216 Proximal, 43, 182, 213, 215 Psoriasis, 215, 219 Psychiatry, 15, 215 Psychic, 177, 199, 201, 215, 220 Psychoactive, 215, 232 Psychogenic, 129, 215 Psychosexual, 129, 216 Puberty, 13, 33, 216 Public Health, 14, 144, 216 Public Policy, 143, 216 Pulmonary, 109, 114, 172, 179, 198, 216, 218, 231 Pulse, 22, 40, 203, 216 Purines, 216, 221 Pyrimidines, 216, 221 Q Quality of Life, 14, 216 R Race, 203, 216 Radiation therapy, 125, 126, 186, 187, 196, 197, 216, 232 Radioactive, 173, 193, 194, 196, 197, 199, 204, 206, 216, 219, 232 Radioimmunotherapy, 216, 217 Radiolabeled, 197, 216, 232 Radiological, 80, 209, 216 Radiology, 125, 216 Radionuclide Imaging, 125, 217 Radiotherapy, 125, 173, 197, 216, 217, 232 Randomized, 84, 183, 217 Reactive Oxygen Species, 65, 86, 217 Reagent, 208, 217 Receptors, Serotonin, 217, 221 Recombinant, 7, 22, 38, 40, 115, 217, 231 Recombinant Proteins, 38, 217 Recombination, 9, 12, 26, 39, 44, 63, 115, 188, 217 Reconstitution, 11, 217 Rectal, 112, 171, 217, 225 Rectum, 169, 173, 178, 182, 188, 195, 198, 214, 217 Red blood cells, 185, 191, 217, 219 Red Nucleus, 170, 217 Reductase, 70, 169, 217 Refer, 1, 124, 173, 178, 187, 199, 204, 205, 216, 217 Reflex, 129, 217 Reflux, 125, 218
Refraction, 218, 223 Refractory, 26, 218 Regeneration, 116, 217, 218 Regimen, 183, 218 Rehabilitation Centers, 5, 218 Renal cell carcinoma, 126, 218 Renal failure, 218 Renal pelvis, 125, 198, 218, 228 Renovascular, 125, 218 Repressor, 45, 207, 218 Reproduction Techniques, 69, 213, 218 Reproductive cells, 187, 189, 218 Reproductive system, 14, 214, 218 Resorption, 187, 218 Respiration, 203, 218 Respiratory System, 204, 218 Response Elements, 34, 218 Restoration, 33, 217, 218, 232 Retinas, 171, 218 Retinoblastoma, 146, 218 Retinoids, 50, 219, 231 Retrograde, 22, 125, 128, 219 Retroperitoneal, 166, 219 Retroviral vector, 188, 219 Retrovirus, 9, 219 Rheumatoid, 208, 219 Rhinitis, 108, 121, 219, 221 Ribonucleoproteins, 206, 219 Ribose, 165, 180, 219 Ribosome, 219, 228 Rigidity, 211, 219 Risk factor, 18, 219 Rodenticides, 210, 219 S Salivary, 182, 208, 219 Salivary glands, 182, 219 Saponins, 219, 224 Scans, 125, 219 Schizoid, 219, 232 Schizophrenia, 219, 220, 232 Schizotypal Personality Disorder, 220, 232 Sclerosis, 146, 169, 170, 220 Screening, 4, 16, 68, 86, 110, 113, 124, 132, 177, 188, 220 Scrotum, 100, 112, 125, 180, 220, 230 Secondary tumor, 202, 220 Secretion, 6, 32, 40, 43, 108, 109, 190, 193, 195, 196, 198, 203, 204, 220, 228 Secretory, 41, 113, 204, 220 Sedimentation, 220, 229 Segmental, 26, 27, 220 Segmentation, 116, 220
244
Male Infertility
Segregation, 25, 28, 217, 220 Seizures, 209, 220 Sella, 210, 220 Semicircular canal, 195, 220 Seminal fluid, 55, 118, 220 Seminal vesicles, 125, 220, 230 Seminiferous tubule, 10, 13, 33, 41, 46, 47, 74, 109, 167, 195, 220 Senescence, 13, 105, 220 Septicaemia, 220, 221 Sequencing, 42, 212, 221 Serine, 114, 197, 221, 229 Serotonin, 57, 205, 217, 221, 229 Serotypes, 55, 221 Serum, 4, 21, 34, 48, 66, 113, 167, 178, 180, 190, 194, 217, 221, 229 Serum Albumin, 21, 221 Sex Characteristics, 167, 206, 216, 221, 226 Sex Determination, 10, 46, 105, 147, 221 Sexually Transmitted Diseases, 124, 125, 221 Shock, 60, 125, 199, 221, 228 Sialyltransferases, 190, 221 Side effect, 42, 135, 166, 172, 221, 227 Signal Transduction, 8, 21, 25, 31, 44, 195, 221 Signs and Symptoms, 124, 222, 229 Sinusitis, 52, 72, 108, 222 Skeletal, 9, 115, 167, 180, 204, 222 Skeleton, 214, 222 Skull, 222, 225 Small intestine, 192, 196, 222, 229 Smooth muscle, 33, 111, 129, 167, 198, 214, 222, 224 Social Environment, 216, 222 Sodium, 25, 222 Solid tumor, 168, 222 Solitary Nucleus, 170, 222 Solvent, 189, 207, 222 Soma, 46, 222 Somatic, 13, 18, 23, 24, 27, 28, 33, 34, 39, 44, 45, 46, 177, 184, 201, 203, 207, 209, 222 Somatic cells, 18, 23, 33, 44, 45, 46, 201, 203, 222 Somites, 116, 222 Specialist, 124, 154, 182, 222 Specificity, 50, 51, 55, 122, 166, 223 Spectrum, 16, 27, 223 Sperm Capacitation, 21, 223 Sperm Count, 20, 34, 40, 110, 116, 120, 223 Sperm Head, 42, 165, 223
Sperm Maturation, 12, 50, 117, 223 Sperm Motility, 12, 24, 37, 52, 75, 110, 120, 223 Sperm Tail, 7, 24, 40, 223 Spermatic, 3, 77, 112, 125, 223 Spermatids, 8, 30, 35, 39, 45, 51, 119, 223 Spermatocyte, 45, 46, 223 Spermatogonia, 33, 44, 223 Spermatozoon, 165, 223 Spinal cord, 4, 55, 87, 115, 129, 176, 201, 205, 209, 218, 223, 225 Spontaneous Abortion, 213, 223 Sporadic, 219, 223 Sprue, 151, 223 Squamous, 50, 223 Staging, 219, 223 Stasis, 125, 223 Stem Cell Factor, 21, 177, 223 Stem Cells, 45, 48, 113, 114, 115, 224 Stenosis, 224 Sterile, 4, 7, 12, 26, 170, 224 Sterility, 25, 44, 48, 51, 56, 60, 61, 66, 67, 68, 71, 72, 76, 81, 84, 85, 86, 87, 89, 91, 113, 195, 224 Steroid, 6, 18, 34, 133, 169, 180, 206, 219, 224 Stillbirth, 213, 224 Stimulant, 197, 224 Stimulus, 179, 182, 185, 197, 218, 224, 226 Stomach, 165, 170, 174, 182, 185, 188, 192, 196, 210, 218, 222, 224 Stool, 178, 195, 198, 224 Strand, 212, 224 Stress, 3, 18, 25, 82, 83, 87, 113, 114, 170, 180, 208, 224 Stricture, 125, 224 Stroke, 11, 37, 101, 142, 224 Stromal, 184, 224 Struvite, 224, 230 Subacute, 195, 222, 224 Subclinical, 195, 220, 224 Subcutaneous, 188, 209, 224 Subspecies, 223, 224 Substance P, 202, 217, 220, 224 Substrate, 24, 106, 224 Sulfur, 186, 207, 225 Superovulation, 15, 225 Suppository, 108, 212, 225 Suppression, 24, 225 Survival Rate, 105, 225 Sympathetic Nervous System, 170, 225 Symphysis, 176, 214, 225
Index 245
Symptomatic, 208, 225 Synaptic, 205, 221, 225 Synaptonemal Complex, 65, 225 Syphilis, 207, 225 Systemic, 109, 136, 172, 185, 195, 197, 216, 225, 228, 232 Systolic, 193, 225 T Telangiectasia, 147, 225 Telecommunications, 179, 225 Telomere, 29, 225 Temporal, 6, 13, 27, 28, 37, 42, 225 Testicle, 3, 190, 225, 230 Testosterone, 6, 12, 13, 18, 21, 33, 34, 36, 48, 73, 78, 109, 112, 113, 217, 226 Thalamic, 170, 226 Thalamic Diseases, 170, 226 Therapeutics, 137, 226 Thermal, 182, 205, 212, 226 Thermography, 84, 226 Thigh, 191, 226 Thorax, 165, 200, 226 Threonine, 221, 226 Threshold, 193, 226 Thrombin, 186, 211, 215, 226 Thrombocytopenia, 113, 226 Thrombomodulin, 215, 226 Thrombosis, 215, 224, 226 Thromboxanes, 169, 214, 226 Thrombus, 180, 195, 204, 211, 226 Thymus, 194, 200, 226 Thyroid, 23, 152, 193, 226, 227, 229 Thyroid Gland, 23, 193, 226, 227 Thyroid Hormones, 227, 229 Thyrotropin, 193, 227 Tinnitus, 207, 227 Tissue, 6, 9, 33, 109, 112, 121, 129, 168, 169, 170, 171, 172, 173, 174, 176, 177, 179, 180, 183, 184, 185, 186, 187, 188, 190, 191, 192, 193, 194, 196, 197, 198, 199, 200, 201, 202, 204, 205, 207, 208, 209, 210, 211, 212, 217, 218, 219, 221, 222, 224, 227, 228, 229, 232 Tomography, 179, 200, 219, 227 Tonal, 111, 227 Tone, 170, 227 Tonicity, 25, 227 Topical, 89, 108, 129, 193, 227 Torsion, 4, 195, 227 Toxic, iv, 6, 33, 99, 100, 105, 120, 184, 212, 227 Toxicity, 182, 202, 227
Toxicology, 19, 70, 144, 227 Toxins, 169, 195, 216, 227 Trachea, 108, 173, 198, 210, 226, 227 Transcriptase, 219, 227 Transcription Factors, 25, 31, 36, 39, 44, 50, 218, 227 Transduction, 21, 221, 227 Transfection, 172, 188, 228 Transfer Factor, 194, 228 Transforming Growth Factor alpha, 228 Transforming Growth Factor beta, 228 Transforming Growth Factors, 10, 228 Transgenes, 23, 44, 228 Transitional cell carcinoma, 4, 89, 228 Translation, 31, 35, 50, 51, 121, 167, 228 Translational, 16, 31, 35, 36, 51, 228 Transmitter, 165, 182, 197, 201, 206, 228 Transplantation, 4, 48, 125, 126, 177, 183, 194, 200, 228 Transurethral, 4, 228 Trauma, 43, 124, 125, 171, 208, 226, 227, 228 Triad, 109, 228 Triage, 123, 228 Trinucleotide Repeat Expansion, 78, 228 Trinucleotide Repeats, 55, 66, 228 Trisomy, 168, 229 Trypsin, 165, 229, 232 Tryptophan, 96, 178, 221, 229 Tuberous Sclerosis, 147, 229 Tubulin, 11, 229 Tumor marker, 172, 229 Tumor Necrosis Factor, 44, 229 Tumor-derived, 228, 229 Tumour, 77, 229 Tyrosine, 21, 31, 49, 182, 229 U Ubiquitin, 120, 229 Unconscious, 193, 229 Uracil, 216, 229, 230 Uraemia, 208, 229 Uremia, 198, 218, 229 Ureter, 115, 125, 193, 198, 199, 218, 228, 229 Urethra, 125, 128, 171, 209, 214, 228, 230 Urethritis, 124, 151, 190, 230 Uridine Triphosphate, 108, 230 Urinary, 4, 49, 89, 108, 124, 125, 126, 129, 174, 180, 184, 189, 195, 206, 230 Urinary Calculi, 124, 230 Urinary tract, 4, 108, 124, 125, 126, 129, 230
246
Male Infertility
Urinary tract infection, 4, 124, 125, 126, 129, 230 Urodynamic, 125, 230 Urogenital, 19, 90, 189, 202, 230 Urogenital Diseases, 230 Urolithiasis, 125, 230 Urologic Diseases, 49, 123, 125, 230 Urologist, 123, 230 Uterine Contraction, 165, 230 Uterus, 165, 176, 180, 183, 184, 201, 207, 213, 218, 230 V Vaccine, 215, 229, 230 Vacuole, 8, 230 Vagina, 176, 181, 201, 218, 230 Vaginal, 121, 225, 230 Valves, 171, 230 Varices, 171, 230 Varicocele, 3, 64, 67, 75, 78, 83, 90, 99, 100, 128, 132, 153, 230 Vas Deferens, 43, 50, 89, 223, 230 Vascular, 46, 91, 125, 195, 198, 199, 202, 207, 210, 214, 226, 231 Vasculitis, 208, 231 Vasectomy, 34, 43, 124, 132, 231 Vasodilatation, 197, 231 Vasodilator, 167, 173, 182, 205, 231 Vector, 9, 196, 227, 231 Vein, 77, 197, 206, 231 Venous, 3, 129, 215, 231 Venter, 86, 231 Ventral, 115, 193, 231 Ventricle, 193, 216, 225, 231 Vertebrae, 223, 231 Vertebral, 222, 231 Vertigo, 207, 231 Vesicoureteral, 125, 231
Vesicular, 67, 191, 231 Vestibule, 178, 195, 220, 231 Veterinary Medicine, 143, 231 Vinblastine, 229, 231 Vincristine, 229, 231 Viral, 61, 105, 219, 227, 231, 232 Virus, 61, 132, 171, 184, 188, 192, 196, 211, 219, 227, 231 Visceral, 170, 231 Visceral Afferents, 170, 231 Viscosity, 120, 231 Vitamin A, 50, 195, 231 Vitro, 4, 20, 21, 33, 35, 36, 39, 47, 48, 50, 55, 64, 73, 94, 104, 105, 106, 110, 113, 119, 120, 175, 183, 188, 195, 212, 232 Vivo, 24, 39, 43, 50, 108, 115, 232 Volition, 197, 232 W Warts, 192, 232 White blood cell, 168, 199, 200, 204, 211, 232 Windpipe, 210, 226, 232 Withdrawal, 29, 232 Womb, 218, 230, 232 Wound Healing, 201, 232 X Xenograft, 168, 232 X-ray, 47, 179, 187, 188, 197, 206, 216, 217, 219, 232 X-ray therapy, 197, 232 Y Yeasts, 187, 210, 232 Z Zona Pellucida, 104, 106, 118, 232 Zygote, 11, 111, 179, 232 Zymogen, 215, 232
Index 247
248
Male Infertility
