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

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

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BIRTH DEFECTS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Birth Defects: 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: 0-597-83788-0 1. Birth Defects-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on birth defects. 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 BIRTH DEFECTS ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Birth Defects ................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 61 CHAPTER 2. NUTRITION AND BIRTH DEFECTS ............................................................................. 105 Overview.................................................................................................................................... 105 Finding Nutrition Studies on Birth Defects .............................................................................. 105 Federal Resources on Nutrition ................................................................................................. 108 Additional Web Resources ......................................................................................................... 108 CHAPTER 3. ALTERNATIVE MEDICINE AND BIRTH DEFECTS ....................................................... 111 Overview.................................................................................................................................... 111 National Center for Complementary and Alternative Medicine................................................ 111 Additional Web Resources ......................................................................................................... 113 General References ..................................................................................................................... 117 CHAPTER 4. DISSERTATIONS ON BIRTH DEFECTS ......................................................................... 119 Overview.................................................................................................................................... 119 Dissertations on Birth Defects ................................................................................................... 119 Keeping Current ........................................................................................................................ 120 CHAPTER 5. CLINICAL TRIALS AND BIRTH DEFECTS ................................................................... 121 Overview.................................................................................................................................... 121 Recent Trials on Birth Defects ................................................................................................... 121 Keeping Current on Clinical Trials ........................................................................................... 121 CHAPTER 6. BOOKS ON BIRTH DEFECTS ....................................................................................... 123 Overview.................................................................................................................................... 123 Book Summaries: Federal Agencies............................................................................................ 123 Book Summaries: Online Booksellers......................................................................................... 125 The National Library of Medicine Book Index ........................................................................... 134 Chapters on Birth Defects .......................................................................................................... 136 Directories.................................................................................................................................. 139 CHAPTER 7. MULTIMEDIA ON BIRTH DEFECTS ............................................................................ 141 Overview.................................................................................................................................... 141 Video Recordings ....................................................................................................................... 141 Bibliography: Multimedia on Birth Defects............................................................................... 142 CHAPTER 8. PERIODICALS AND NEWS ON BIRTH DEFECTS ......................................................... 143 Overview.................................................................................................................................... 143 News Services and Press Releases.............................................................................................. 143 Newsletter Articles .................................................................................................................... 146 Academic Periodicals covering Birth Defects............................................................................. 148 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 149 Overview.................................................................................................................................... 149 U.S. Pharmacopeia..................................................................................................................... 149 Commercial Databases ............................................................................................................... 150 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 155 Overview.................................................................................................................................... 155 NIH Guidelines.......................................................................................................................... 155 NIH Databases........................................................................................................................... 157 Other Commercial Databases..................................................................................................... 160 The Genome Project and Birth Defects ...................................................................................... 160

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APPENDIX B. PATIENT RESOURCES ............................................................................................... 167 Overview.................................................................................................................................... 167 Patient Guideline Sources.......................................................................................................... 167 Associations and Birth Defects .................................................................................................. 177 Finding Associations.................................................................................................................. 179 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 181 Overview.................................................................................................................................... 181 Preparation................................................................................................................................. 181 Finding a Local Medical Library................................................................................................ 181 Medical Libraries in the U.S. and Canada ................................................................................. 181 ONLINE GLOSSARIES................................................................................................................ 187 Online Dictionary Directories ................................................................................................... 187 BIRTH DEFECTS DICTIONARY ............................................................................................... 189 INDEX .............................................................................................................................................. 247

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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 birth defects 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 birth defects, 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 birth defects, 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 birth defects. 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 birth defects, 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 birth defects. The Editors

1

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

3

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and birth defects, 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 “birth defects” (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: •

Dentist's Role: The Unnecessary Epidemic of Folic Acid-Preventable Birth Defects, Spina Bifida and Anencephaly Source: Virginia Dental Journal. 79(3): 24-25. July-September 2002. Contact: Available from Virginia Dental Association. 7525 Staples Mill Road, Richmond, VA 23228. (804) 261-1610 or, in Virginia, (800) 552-3886. Summary: This article familiarizes dentists and dental care professionals with folic acidpreventable birth defects, notably the neural tube defects (NTDs), spina bifida and anencephaly. Prevention of most NTDs is possible if all women in the perioconceptional period have high enough body content of folic acid (a B vitamin). The author reviews neural tube formation and prevention of NTDs, and the role of health care providers in reducing the risk of NTDs. The author notes that many women of childbearing age, who

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may not yet be pregnant, visit dentists on a regular basis for preventive dental exams. Thus, dentists are in a unique position to provide information about folic acid and the prevention of NTDs, as it is most effective if taken before and during early pregnancy. 7 references. •

Meeting the Challenges of Craniofacial-Oral-Dental Birth Defects Source: JADA. Journal of American Dental Association. 127(5): 681-682. May 1996. Summary: This article reminds readers of the relatively common occurrence of infants born with some type of craniofacial birth defect, including cleft lip. The author stresses that over the child's first 10 to 15 years of life, he or she may require the care from a wide spectrum of health care providers, including pediatrics, genetics, anesthesiology, oralmaxillofacial surgery, plastic surgery, otolaryngology, pedodontics, orthodontics, prosthodontics, nursing, and social and psychological service providers. The author also discusses the risk factors associated with craniofacial birth defects; preventing these birth defects; the impact of some prescription drugs, alcohol, and smoking on birth defects; and prenatal development of the craniofacial structures. The author stresses the potential role that dentists can play as advocates for health promotion and birth defect prevention. A list of resource organizations is provided for readers wishing to obtain additional information.

Federally Funded Research on Birth Defects The U.S. Government supports a variety of research studies relating to birth defects. 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 birth defects. 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 birth defects. The following is typical of the type of information found when searching the CRISP database for birth defects: •

Project Title: A GENETIC PATHWAY REQUIRED FOR PHARYNGEAL ARCH DEVELOPMENT Principal Investigator & Institution: Baldini, Antonio; Associate Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Functional analysis of the murine chromosomal segment, homologous to the human region deleted in DiGeorge syndrome, identified a

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

5

putative transcription factor, Tbx1, required for the development of the pharyngeal apparatus. Homozygous mutation of Tbx1 leads to severe disruption of pharyngeal arches 1-2, and absence of pharyngeal arches 3-6. The pharynx lacks the characteristic segmented pattern to assume a tube-like morphology. On the basis of the mutant phenotype, we hypothesize that Tbx1 has multiple roles in the development of the pharyngeal apparatus. This hypothesis cannot be addressed with the current germ-line mutation model because the early requirement of Thx 1 prevents us from testing gene function later in development. To address our hypothesis we propose to develop and test an in vivo conditional system for positive and negative regulation of Tbx1 expression. First we will construct and test the system, and subsequently, we will establish the temporal requirement of Tbx1 expression, and the role of Thx 1 after the initial pharyngeal endoderm patterning. Tbx1 mutants present one of the most dramatic and yet specific pharyngeal phenotypes so far reported. The strategy proposed here is intended to address a broad range of questions concerning the development of the pharyngeal apparatus. This is because the tools generated will allow us to modulate the development of this complex structure. Developmental problems of the pharyngeal apparatus underlie many birth defects, including relatively common craniofacial and cardiovascular abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A PROGRAM OF RESEARCH IN POPULATION CYTOGENETICS Principal Investigator & Institution: Hassold, Terry J.; Professor of Genetics; Genetics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-JAN-1988; Project End 31-MAR-2005 Summary: Trisomy is a most common genetic abnormality in our species, occurring in at least 3-4 percent of all clinically recognized pregnancies. Despite this high incidence and obvious clinical importance, the causes of human nondisjunction remain unclear. In this proposal, we outline a series of cytogenetic and molecular experiments to study the genesis of trisomy in humans. In one set of studies, we will analyze exchange patterns in trisomy-generating meioses; this will allow us to examine the effects of altered recombination on nondisjunction of different chromosomes and nondisjunction involving women of different ages, and to determine whether genome-wide alterations in recombination are a feature of nondisjunctional meioses. Secondly, we propose to investigate the effect of putative environmental agents on trisomic spontaneous abortions; in particular, we will focus on factors recently suggested to play a role in the genesis of trisomy 21. Finally, we intend to develop mouse models of human nondisjunction, utilizing situations in which pairing and recombination is disturbed (inversion heterozygotes) or abolished (minichromosome-carrying homozygotes); if successful, this approach would yield the first useful animal models of human meiotic nondisjunction. These studies parallel those proposed by Dr. Stephanie Sherman in the companion IRPG application. Indeed, with the exception of the murine studies of the present application and the analysis of birth defects in Dr. Sherman's application, the questions and methodological approaches are nearly identical. By combining a large, population-based analysis of trisomy 21 with analyses of other autosomal and sex chromosome trisomies, we intend to characterize the genesis of the most common and clinically important human chromosome abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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•

Project Title: ACTIVIN GASTRULATION

RECEPTORS

AND

SMAD2

IN

MAMMALIAN

Principal Investigator & Institution: Brissette, Janice L.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The transforming growth factor-beta (TGF-beta) superfamily molecules play critical roles in a diverse range of developmental processes. Our long term goal is to understand the signaling mechanism by which TGF-beta family factors regulate morphogenesis. Mesoderm induction and gastrulation are key events that lead to the establishment of body axes. Members of the TGF-beta family such as activins, Vg-1, nodal, and BMPs are potent mesoderm inducing factors and function during early development in vertebrate animals. The signaling cascade and the developmental program activated by activin or BMP has been extensively studied in Xenopus and chick early embryos. However, it remains unclear whether these signaling pathways are conserved in mammals. Genetic studies have demonstrated that nodal and BMP4, but not zygotic activins, are essential for early mouse development. To investigate the function of activin type I and type II receptors and a downstream signal mediator Smad2 in mammalian development, mutant mice have been generated by targeted disruption of the corresponding genes in mice. Genetic and embryological studies of the mutant mice have provided direct evidence that activin receptors and Smad2 are essential for mesoderm formation and gastrulation. To further analyze the function of activin receptor- and Smad2- mediated signaling pathways in the regulation of cell growth and differentiation, primitive streak formation and gastrulation, the following specific aims are proposed: (1) To understand how activin receptors and Smad2 regulate embryo growth, germ layer organization, and cell fate determination during egg cylinder formation and gastrulation. (2) To investigate how activin receptors and Smad2 regulate primitive streak formation and mesoderm patterning. 3) To investigate the function of nodal, BMP4, and chordin and their signaling pathways in primitive streak formation. Methods such as chimera (or mosaic) analysis through microinjection of blastocysts or aggregation of tetraploid embryos with ES cells, in situ hybridization, lineage analysis with lacZ-marked mutant ES cells, and ES cell-mediated gene delivery will be applied in this project. These aims, once accomplished, will lead to a better understanding of the signaling mechanism that controls early mammalian development. The knowledge acquired regarding early embryonic development will be useful for understanding later developmental processes such as organogenesis and will have important implications towards understanding the genetic basis of various forms of birth defects in human. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALCOHOL AND CELL ADHESION Principal Investigator & Institution: Charness, Michael E.; Professor; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's Abstract) Ethanol inhibits cell adhesion mediated by the L1 cell adhesion molecule in neural cells and fibroblasts transfected with human L1. Because the brains of children with L1 mutations resemble those of children with fetal alcohol syndrome, it is possible that inhibition of L1-mediated cell adhesion contributes to the teratogenic effects of ETOH. Structure activity analysis of a series of straight and branch-chain alcohols demonstrates remarkable structural

Studies

7

specificity for alcohol inhibition of cell-cell adhesion. Moreover, we have identified a series of compounds that antagonize the effects of ethanol on L1-mediated cell-cell adhesion, on BMP morphogenesis in cultured neural cells, and on the development of mouse whole embryo cultures. The underlying hypothesis of this proposal is that compounds that antagonize ethanol inhibition of L1-mediated cell-cell adhesion will also antagonize ethanol teratogenesis. The proposed research has three specific aims: 1. To identify the structural determinants of alcohols and related compounds that are required for inhibition of cell-cell adhesion in L1-expressing cells and for antagonism of this inhibition; 2. To characterize regions of L1 that are necessary for alcohol inhibition and for antagonism of ethanol inhibition; 3. To evaluate selective ethanol antagonists for their ability to prevent the teratogenic effects of ethanol in mouse whole embryo culture and during early embryogenesis in C57BL/6J mice. Techniques employed in these studies will include mammalian cell transfection, cell-aggregation assays, mutagenesis of the L1 molecule, mouse whole embryo culture, and macroscopic and microscopic analysis of mice exposed to ethanol in utero. These experiments may lead to a better understanding of how ethanol interacts with neural proteins and may reveal mechanisms whereby ethanol causes birth defects. A major goal of the proposed research is to identify compounds that reduce the teratogenic effects of ethanol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DROSPHILIA

ANALYSIS

OF

EARLY

WING

VEIN

DEVELOPMENT

IN

Principal Investigator & Institution: Bier, Ethan; Biology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: (adapted from investigator's abstract): The long term goal of this proposal is to understand how wing vein development is initiated in Drosophila wing imaginal discs. Five major veins run the length of the Drosophila wing. We have proposed that wing vein development is initiated at boundaries between distinct domains of cells situated along the anterior-posterior (A/P) axis of the wing imaginal disc in third instar larvae. In our convincing case for this hypothesis, we have provided a variety of evidence indicating that development of the second longitudinal vein (L2) is induced just anterior to a broad central domain of cells expressing a zinc finger transcription factor known as spalt- major (salm). We have proposed that salm expressing cells send a signal to adjacent anterior cells to activate expression of hormonereceptor family transcription factors encoded by genes at the knirpslknirps-related (kni/knrl) locus. The kni and knrl genes then function to organize gene expression in and around the L2 vein primordium. In this proposal we seek to understand the mechanism by which salm expressing cells activate kni and knrl expression in neighboring anterior cells by analyzing an enhancer element of the knilknrl locus which drives expression in the L2 primordium. We also propose to investigate the regulation of a second gene, abrupt (ab), which functions to organize formation of the L5 vein. In a key experiment, we propose to determine whether the kni~nrl and ab genes define specific vein types (i.e. L2 versus L5) or whether they function more generally in promoting vein versus intervein fates. These studies are of broad medical relevance to understanding the basis of birth defects. As defects in cell-cell signaling are involved in disease states such as cancer, the proposed studies also are relevant to such diseases since development of the L2 vein depends critically on cell-cell communication. In addition, the TGF-8 related signaling and EGF-R signaling pathways play prominent roles in maintaining and refining the vein pattern. Because mis-regulation of these known pathways causes

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aggressive forms of cancer, understanding the regulation of these pathways also is of significant relevance to cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS DROSOPHILA

OF

RHOA

MEDIATED

MORPHOGENESIS

IN

Principal Investigator & Institution: Halsell, Susan R.; Biology; James Madison University Harrisonburg, Va 22801 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant) Morphogenesis remodels the shape of the embryo, generating the myriad of complex forms and structures that characterize the mature organism. Defects in morphogenesis give rise to birth defects such as spina bifida and anencephaly. While the outcome of such morphogenetic defects is very apparent, the underlying cellular and molecular mechanisms of normal morphogenesis remain unclear. Investigating and characterizing morphogenesis is an important step understanding how to overcome birth defects. The studies proposed here focus on key a cellular aspect of morphogenesis, the generation of cell shape changes; signal transduction via the small GTPase molecular switch, RhoA, is critical for these cell shape changes. This proposal will extend previous studies, directly investigating the role of RhoA signal transduction during morphogenesis of Drosophila melanogaster. This allows exploitation of the powerful molecular and classical genetic techniques afforded by the model organism. This research will examine the precise nature of the defects in RhoA and RhoGEF2 mutant animals. This will be accomplished by utilizing fixed preparations of mutant embryos that have been stained with antibodies directed against the cytoskeleton. New mutant alleles of RhoA and its positive regulator, Rho Guanine Exchange Factor 2, will be generated in order to further define the morphogenetic processes that require Rho signal transduction. This will include standard chemical mutagenesis techniques and the generation of a conditional RhoA mutation. The relationship between Rho signal transduction and Myosin activation will be explored. This will be accomplished by molecularly engineering a myosin transgene and then expressing it in RhoA mutant embryos. Finally, powerful genetic strategies will be used to identify molecules that function upstream and downstream of Rho signal transduction. Tissue culture and biochemical studies have suggested a number of players in this process, but their biological relevance in the intact organism remains unclear. We will test these candidate loci directly in genetic interaction tests with RhoA mutations. Further, we will perform mutagenesis screens to identify novel gene products that collaborate in the Rho signal transduction pathway. Together, these studies will extend understanding of the fundamental role and pathways Rho signal transduction plays in morphogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANEUGEN SCREENING IN OPTIMIZED YEAST STRAINS Principal Investigator & Institution: Hughes, Owen L.; Eon Corporation 635 Anderson Rd, Ste 11 Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: (provided by applicant): Although aneuploidy is responsible for significant adverse human health conditions such as birth defects, mental retardation, spontaneous abortions, and cancer, little is known about the possible aneugenicity of the chemicals and drugs we are exposed to. In Phase I work, a novel Saccharomyces cerevisiae-based

Studies

9

chomosome nondisjunction assay was developed for eventual use in high throughput screening. This nondisjunction assay has a simple fluorometric readout and responds to known aneugens. Here, the assay will be adapted to an economical high throughput format. In addition, methods for increasing the predictive value of yeast-based tests will be explored in two ways. First, methods for decreasing the pharmacokinetic differences between yeast and mammalian cells including 1) increasing drug uptake, 2) decreasing drug excretion, and 3) mimicking mammalian metabolism of test compounds will be explored. Second, two different types of "first hit" sensitizing mutations--centromere mutations and mitotic checkpoint mutations-- will be examined. Finally, the nondisjunction assay will be combined with a DEL-like assay to allow simultaneous assessment of both aneugenicity and carcinogenicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AXONAL AND DENDRITIC DIFFERENTIATION IN GRANULE NEURONS Principal Investigator & Institution: Carr, Catherine E.; Professor; Zoology; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-MAY-2003 Summary: The objective of this proposal is to understand the mechanisms that control axonal and dendritic differentiation and morphology in granule neurons. To determine how cues intrinsic to the cell, or present in the extracellular environment, direct the differentiation and maturation of granule cell axons and dendrites, the following hypotheses will be tested: 1) The initial site of unipolar process extension is determined by the cytoplasmic location of the Golgi apparatus; after unipolar extension, the GA reorients within the cytoplasm to support the growth of the second axonal process. To test this hypothesis, time-lapse confocal microscopy will be used to determine the dynamic behavior of the GA during the initial stages of granule clel axon outgrowth in. 2) After initial bipolar parallel fiber (PF) axon outgrowth is completed, diffusible or contactmediated signals from developing Purkinje cells (PC) and/or granule cells within the molecular layer (ML) cause a down-regulation in expression of the axonal cell adhesion molecule, TAG-1, on granule cells located at the deep external granule layer (EGL)/ML border. To test this hypothesis, it will determined whether granule cell/PC contact in , or conditions that mimic the onset of synaptic activity between granule cells and Pcs, provide an "off-signal" for TAG-1 expression on initial granule cell axons. 3) Exposure of immature granule cells to depolarizing conditions inhibits axonogenesis and promotes dendritic differentiation. To test this hypothesis, immature granule cells will be exposed to depolarizing condition from the time of plating in. 4) Complete granule cell dendritic differentiation, which is characterized by the formation of characteristic claw-like dendrites, proceeds only after direct cell-cell contact with mossy fiber afferents. To test this hypothesis, granule cells will be co-cultured with pontine explants to provide a source of mossy fiber afferent input, to determine whether direct cell-cell contact with mossy fibers 'drives' further dendritic differentiation. Understanding the mechanisms that control the normal differentiation of granule neurons is critical in understanding the etiology of the various cerebellar ataxias and birth defects such as fetal alcohol syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: 'CANCER EDUCATION GRANT PROGRAM' Principal Investigator & Institution: Burzynski, Norbert J.; Professor and Chairman; Diagnostic Radiology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The objective of the present application is to continue the long-standing, highly successful, short-term research program in Cancer Biology at the University of Louisville. The current program has been the recipient of over twenty years of near-continuous NIH support. Throughout the tenure of this program, the highest priority has been given to disseminating, to health professional students, an appreciation for issues in cancer biology as they relate to diagnosis, prevention and treatment of the disease, from a clinical and research perspective. The current program provides a unique venue for student - faculty interaction, and provides highly motivated and qualified students with the opportunity to gain exposure to cancer biology and enhance their knowledge in this area through weekly Tumor Board conferences, Program Workconferences, special programmatic seminars, a "Cancer Careers Minisymposium," laboratory research, and presentations at local/national meetings. The present application has been revised substantially with regard to training faculty, outcomes assessment procedures, and special initiatives to increase student awareness of career opportunities in cancer health care and research. A new Health Science Center-wide training venture has been initiated, which benefits from the participation of eighteen core faculty, all of whom are funded extensively through federal/foundation sources and have a demonstrated commitment to biomedical research and education. This multidisciplinary group represents a forging of research and training partnerships spanning seven University departments and incorporating the University of Louisville Schools of Dentistry and Medicine, J. Graham Brown Cancer Center, Birth Defects Center, Center for Genetics and Molecular Medicine, and Kosair Children's Hospital Research Institute. Seventeen of the program Core Faculty are participating members of the J. Graham Brown Cancer Center. All have committed to provide trainees with exposure to, and involvement in, contemporary research programs in varied aspects of cancer biology and molecular mechanisms of cellular growth control. A noted cancer epidemiologist from the MD Anderson Cancer Center has been enlisted as a consultant to develop and execute a systematic strategy for program evaluation and trainee tracking, and to function as an educational advisor for the program. In summary, it is the objective of our program to provide a unique and contemporary educational venue in cancer biology, designed to train the next generation of academic clinical scientists. These individuals will be poised to enter the fields of cancer health care and research, and have a long-term impact on reducing cancer incidence, mortality and morbidity.the foremost theme of cancer prevention through cancer biology! Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER IN THE JERUSALEM PERINATAL STUDY COHORT Principal Investigator & Institution: Harlap, Susan; Research Professor; Obstetrics and Gynecology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-MAR-2003 Summary: The Jerusalem Perinatal Study is a population-based research data bank based on mothers, fathers and offspring. In 1964-76 all Jewish births were surveyed, as were all births to Arab residents of West Jerusalem. Demographic data were recorded

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on the parents, infant deaths and congenital malformations, admissions to hospitals and obstetric complications. Approximately two thirds of the Jews were refugees, or their offspring, from Morocco, Algeria, Tunisia, Egypt, Iraq, Iran, Turkey, Yemen, Syria or Lebanon. Specific subsets of the mothers were interviewed in 1966-68 and 1975-76, adding information on consanguinity, antenatal health, body size, smoking, fertility, gynecologic variables and contraceptive use. After an average of 27 years (range 21-33) most offspring have completed their compulsory military service. This cohort may be one of the largest to include ethnic ancestry with obstetric and social data, which can link siblings and parents. We propose to link this database with Israel's Cancer Registry for follow-up studies of malignancies, as the parents and offspring age, and to prepare for the potential use of this cohort for cancer prevention trials. In this initial 4-year project we will undertake the checking and corrections needed for record linkage, describe losses to follow up, identify deaths and update the record linkage annually. Linkage in 1999 will identify malignancies diagnosed to the end of 1996, including an estimated 1846 cases in the 34,900 mothers and 485 in the 92,500 male and female offspring. We estimate there will be 440 cancers of breast and 122 of ovary, half of them to women of non-European origin. Focussing on breast cancer in mothers we will test for effects of gender of first offspring and explore ethnic differences in the effects of these and conventional risk factors. We will question whether changes in incidence of breast cancer and or other cancers can be predicted by births of offspring with major or minor birth defects, including neural tube defects and Down's syndrome, or by certain obstetric outcomes, including pre-eclampsia. The results may identify women who would benefit from intensive screening or provide new clues to the etiology of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL NEURULATION

MOTILITY

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CELL

INTERACTIONS

DURING

Principal Investigator & Institution: Keller, Raymond E.; Professor; Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-MAR-2007 Summary: (provided by applicant): The broad aim is to determine the tissue interactions and signaling pathways that control a specific type of polarized cell motility that occurs during "convergence and extension" (narrowing and elongation) movements of the embryonic nervous system of the frog, Xenopus laevis, and to test the role of this motility in forming the neural tube. Past work identified a monopolar, medially-directed cell motility that causes neural cells to intercalate between one another, thus narrowing and elongating the neural plate. Previously unknown signals from the midline tissues of notochord/notoplate were discovered to control this polarized motility, and a model of how this motility is regulated by the midline was developed. The proposed research uses state of the art fluorescent cell labeling, fluorescence microscopy, and digital imaging methods to describe cell movements in cultured explants, and in recombinations of embryonic tissues, designed to test the specific tissue interactions hypothesized to control the polarized cell motility. Molecular perturbations of molecules thought to control this motility will be targeted to specific cells at specific times, using transgenic lines of X. laevis and the Ga14/UAS system from Drosophila. The specific aims are to: 1. further characterize the polarized and oriented motility of deep neural plate cells and the signals from the midline tissues that induce this motility, using our model as a guide for experiments; 2) determine the role of the planar cell polarity pathway in regulating this polarized and oriented cell behavior; 3) determine the role of

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small GTPases in controlling cell motility in neural plate morphogenesis. This work will provide a deeper understanding of the cell motility that forms the neural tube in vertebrates, and how this motility is controlled by specific tissue interactions and signaling pathways. These findings will contribute to understanding the failure of human birth defects, such as spina bifida, in which the neural does not form and close properly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR MORPHOGENESIS

AND

MOLECULAR

BASIS

OF

MELANOCYTE

Principal Investigator & Institution: Erickson, Carol A.; Professor of Molecular and Cellular Biol; Molecular and Cellular Biology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-JUL-2003 Summary: The long term goal of this research is to define in molecular detail the factors that control embryonic morphogenetic movements. Cells of the neural crest will be used to address fundamental questions concerning cell migration in the embryo. Neural crest cells give rise to a myriad of derivatives, each of which migrates and localizes to specific sites during embryogenesis. The previously accepted model for patterning neural crest derivatives proposed that neural crest cells are a pluripotent population of cells that migrate haphazardly into the various pathways and differentiate according to cues encountered in these paths. New evidence shows that an alternative mechanism guides melanoblasts (pigment cell precursors). Specifically: 1) melanoblasts are fate-specified prior to their migration from the neural tube, 2) only neural crest cells that are fatespecified as melanoblasts enter the dorsolateral path (i.e the path to the skin) and 3) under experimental conditions, melanoblasts are the only neural crest subpopulation that can exploit the dorsolateral path. This means that some neural crest subpopulations are specified prior to or shortly after they separate from the neural tube, and owing to molecular changes accompanying specification they are able to migrate in the appropriate path. In the next funding period we propose to extend this work by addressing the following Specific Aims: 1. To determine what molecular changes allow melanoblast migration into the dorsolateral path. 2. To determine what molecular changes control the specification of the melanoblast lineage. 3. To use a differential display strategy to determine what genes are expressed preferentially in the dorsal neural tube at the time that melanoblasts are being specified. 4. To determine whether prior specification of some neural crest subpopulations at the vagal level control pathway choice. Defects in neural crest morphogenesis are some of the most common birth defects and these studies may reveal their underlying basis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF THE MOUSE CPO1 MUTATION Principal Investigator & Institution: Bjork, Bryan C.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Non-syndromic cleft secondary palate (CP) is one of the most common human birth defects. It has a very complete etiology that includes strong genetic, likely polygenic, and environmental contributions. Although many embryological studies in model organisms and linkage and association studies in humans have provided insight into this complexity the developmental and genetic basis

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for normal palate development remains incompletely understood. The study of palatal development in isogenic mouse strains carrying Mendelian mutations in a controlled environment avoids confounding influences as allelic heterogeneity and environmental insults. Specifically, I propose to initiate studies of mouse mutation with an isolated cleft secondary palate phenotype, cleft palate only 1 (cpo1), as an entry point into the understanding of a specific gene whose function and interactions in a genetic pathway(s) is essential to norm; palatogenesis. I have used a positional cloning strategy to rapidly clone the causative gene for cpo1, the Prdm16 (alias, Mel1) Zn-finger transcription factor. I will use the cpo1 mutant to elucidate the specific developmental defect in palatogenesis caused by the Prdm16 gene mutation and analyze the pattern of Prdm16 gene and protein expression during embryogenesis and palatogenesis in wildtype mouse embryos. Using in situ hybridization and immunohistochemistry, I will assay the expression of genes and proteins that mark specific stages and structures during palatogenesis to identify putative members of a common genetic pathway affecting normal palate development. Finally, downstream targets and DNA-binding sites of the Prdm16 protein will be identified through hybridization to DNA binding arrays and co-immunoprecipitation experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC POSTNATAL ALCOHOL AND ATTENTION IN THE RAT Principal Investigator & Institution: Hunt, Pamela S.; Psychology; College of William and Mary Williamsburg, Va 23187 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: Absent from animal research on alcohol-related birth defects (ARBD) is a systematic analysis of ethanol-induced alterations in basic attentional mechanisms. The proposed research will employ measures of the orienting response, a collection of central, autonomic, and behavioral responses elicited by novel stimuli and believed to index the central process of attention in both animals and humans. The long-term objective of the proposed research is to rigorously investigate basic measures of attention, and to determine how they relate to attentional deficits in an animal model of ARBD. ARBD human infants are known to be impaired in the expression of some of these responses, and further knowledge about these measures may ultimately prove useful as part of a neonatal diagnostic for later attentional dysfunction. These experiments will utilize a postnatal alcohol administration procedure that has been effectively used for studying neuroanatomical changes associated with ARBD. Animals will be intragastrically administered alcohol from postnatal days 4 through 9. In all these experiments ethanol-exposed rats will be compared with controls that will either be sham intubated or handled only. The first experiment will involve measuring bloodand brain-alcohol levels on day 9, both in a chronic ethanol group and in a group of acutely-exposed subjects. The design allows for the assessment of metabolic tolerance to ethanol, and will also provide information about alcohol levels achieved - an important determinant of alcohol's teratogenic effects. The second experiment will examine the effects of postnatal alcohol exposure on the functional development of the autonomic nervous system (ANS) at 12 and 16 days of age. A major component of the orienting response consists of a change in the activity of the parasympathetic division. This experiment will examine possible ethanol-induced alterations in baseline autonomic regulation as well as that of the cardiac response to a novel olfactory stimulus. The third and final experiment will assess ethanol- induced deficits in response habituation and short-term retention for both olfactory and auditory stimuli in preweanling animals. Deficits in response habituation and short-term recognition memory have been reported

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in FAS/ARBD infants. By systematically evaluating orienting responses, habituation and retention a fuller understanding of these responses and how they are affected by FAS/ARBD will be gained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLABORATIVE GENETICS RESEARCH TRAINING PROGRAM Principal Investigator & Institution: Jabs, Ethylin W.; Professor and Director; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 22-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This grant application proposes to create a new research-training program in genetics for students, researchers, and professionals from the developing country, People's Republic of China. This collaborative program will be developed between The Johns Hopkins University and two major institutions in Beijing, Peking Union Medical College and Peking University. This program will train researchers in the principles of genetic research on complex disorders such as birth defects and chronic diseases. The Training Advisory Committee and faculty from Hopkins have expertise in clinical genetics, molecular genetics, statistical genetics, population genetics, bioinformatics, and epidemiology. Expertise on the ethical, social, and legal implications of human genetics research will also be an integral part of our curriculum. Short term trainees from China will enroll in established courses such as the Graduate Summer Institute of Epidemiology and Biostatistics at The Johns Hopkins Bloomberg School of Public Health and the Short Course in Medical and Experimental Mammalian Genetics co-sponsored by The Johns Hopkins Institute of Genetic Medicine and The Jackson Laboratory at Bar Harbor. Long-term trainees will enroll in a Master of Public Health, Master of Science in Genetic Counseling, or research laboratory training, some of whom may obtain certification in Clinical Molecular Biology, Biochemical Genetics, or Cytogenetics. Predoctoral students will enroll in degree programs for a Ph.D. in Human Genetics and Molecular Biology, Epidemiology, or Biostatistics. After the training, fellows and students will return to China to develop their own research and strengthen the "genetics research culture" in Beijing and beyond. The Johns Hopkins University School of Public Health conducts more international health research than any other school in the country. Johns Hopkins offers strong training programs in epidemiology, biostatistics, and bioethics appropriate for scientists from developing countries. We have confidence in our ability to provide relevant, practical, and flexible training to these visiting professionals, as well as to ensure smooth and successful transition in bringing genetic research to China. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTROL OF NEUROBLAST PROLIFERATION IN DROSOPHILA Principal Investigator & Institution: Datta, Sumana; Associate Professor; Biochemistry and Biophysics; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 15-DEC-1998; Project End 31-MAY-2003 Summary: The long-term goal of this project is to elucidate the molecular mechanism(s) controlling stem cell proliferation and differentiation in response to developmental and physiological cues. Stem cells are a unique subset of precursor cells which are selfrenewing and capable of giving rise to a wide variety of differentiated progeny. Furthermore, insufficient stem cell division can lead to birth defects, while uncontrolled division can lead to many types of cancer. Thus, stem cells have an enormous impact on the health, viability and the maintenance of all organisms. In Drosophila, subsets of

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neuronal stem cells, or neuroblasts, are quiescent upon larval hatching and resume cell division at specific developmental stages during larval growth; the timing of neuroblast proliferation is affected by mutations in two genes: trol and ana. ANA is required to repress premature neuroblast division and TROL is required to initiate neuroblast division inhibited by ANA. Indirect evidence suggests that ANA must be secreted by the glial cells in order to function. This hypothesis will be tested by constructing a gene for a secretion-defective ANA protein and determining if this gene can provide normal ana function. We will also examine ANA localization by immunoelectron microscopy, and bypass the specific cell cycle steps blocked by ANA by induced expression of various cell cycle genes. To understand how trol stimulates neuroblast activation, the trol gene will be isolated and the sequence of the TROL protein analyzed for similarities with known proteins in the database. These results will be supplemented with analysis of the spatial and temporal patterns of distribution of trol transcripts and TROL protein. Both trol and ana must eventually transmit their signals to the cell cycle machinery to control neuroblast proliferation. We will use biochemical and molecular approaches to identify proteins in the signaling pathways and genetic and molecular analysis to examine the role of the transcription regulator evenskipped in the trol pathway. Finally, potential coordinate control of neuroblast proliferation by ana and trol will be addressed by examining trol transcription and TROL localization in an ana mutant background. These studies will provide important insights into the mechanism by which proliferation of stem cells is controlled by developmental cues, and will generate new tools and reagents to probe further into these mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--HEALTH REGISTRY Principal Investigator & Institution: Lynch, Charles F.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 29-SEP-1990; Project End 31-MAR-2006 Summary: The aims of the Health Registry Facility (HRF) are to provide data and services to investigators wishing to use any of its five participating units: the Iowa Cancer Registry, the Iowa Birth Defects Registry, the Center for Health Effects of Environmental Contamination (CHEEC), the Rural Injury Surveillance System (RISS), and an asthma database still under development. The HRF also provides access to the Agricultural Health Study Registry. In addition to access to these registries, the HRF personnel offer a variety of services related to the use of these databases, including survey design, sampling, programming, and database linkage. The Registry has been used in Iowa?s studies of residential radon and its participation in the Agricultural Health Study, and has facilitated other research projects such as the Iowa Women?s Health Studies. Future directions involve integration of the Birth Defects Registry and asthma database into the core facility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CSPG2 GENE AND CARDIAC OUTLET MORPHOGENESIS Principal Investigator & Institution: Mjaatvedt, Corey H.; Cell Biology and Anatomy; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Our observations of the heart defect (hdf) null embryo has provided remarkable evidence that the Cspg2 gene (versican) has an unexpectedly important role in the growth and differentiation of the outlet segment

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Birth Defects

(conotruncus) of the heart. We propose to determine the critical role of versican in a region that is a "hot spot" for clinically important birth defects affecting over one-half of all human live birth heart defects. The conotruncus of the developing outlet forms from a previously unrecognized mesodermal heart field located anteriorly to the primitive ventricle. We propose the Cspg2 gene promotes differentiation and stabilization of the myocardial phenotype as a contractile and inductive signaling tissue in the growing conotruncus. Our hypothesis is that 1) specific functional domains of Cspg2 are required for normal myocardial recruitment in the growing outlet and 2) the programmed loss of the truncus myocardium during the late remodeling stages results from the absence of specific functional domains of Cspg2. An abnormal loss or other variation of versican expression at the early recruitment or later remodeling stages, affects the normal patterns of phenotypic stabilization in the truncus myocardium and results in conotruncal heart defects. We propose the following Specific Aims: 1) To determine the expression patterns of Cspg2 functional domains in the developing conotruncus during (a) early recruitment of the myocardium from the anterior heart field mesoderm (AHF) and during (b) later stages when the truncal myocardium is known to regress; 2) To test the hypothesis that Cspg2 functions to stabilize the conotruncus phenotype by overexpressing Cspg2 in a whole animal transgenic mouse model.; 3) To determine if specific Cspg2 functional domains are required for recruitment and/or stabilization of the conotruncus myocardium's contractile and inductive signalling phenotypes; 4) To determine if specific domains of the Cspg2 protein have a functional role later in contruncal development to remodel the truncus by destabilizing the myocardium for transdifferentiation into a fibrous connective tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYCLIC NUCLEOTIDES AND THE RESPONSE TO SONIC HEDGEHOG Principal Investigator & Institution: Roelink, Henk; Assistant Professor; Biological Structure; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-JAN-2004 Summary: The Sonic Hedgehog is a signaling molecule that is required for normal development of the central nervous system. The response to Shh is complex, and can be changed by environmental compounds like cyclopamine. Changes in the Shh response result in a specific type of embryo malformations characterized by defects of the neural midline, like holoprosencephaly, which can be reflected in the face as cyclopia or hypotelorism. All cell types in the ventral neural tube develop as a consequence of Shh signaling, and it is likely that small changes in the Shh response has subtle effects on the formation of ventral cell types. This in turn might result in congenital neurological defects. It has been determined that the Shh response is influenced by the cyclic nucleotide concentration within the responding cells. Increasing the camp concentration attenuates the Shh response, while loss of the camp dependent kinase (PKA) activates the Shh response. These authors showed that increasing the cGMP concentration also enhances the response to Shh, suggesting a model in which the Shh response is dependent on the cyclic nucleotide concentration within the responsive cells, and that camp and cGMP have opposite effects on the Shh response. Several compounds present in the environment can alter the intracellular cyclic nucleotide concentration, either by activating GTP/ATP cyclases, enzymes that generate cyclic nucleotides, or by blocking phosphodiesterases, enzymes that degrade cyclic nucleotides. It is hypothesized that environmental compounds that change the cyclic nucleotide complement of a cell, alter Shh response in such cells, resulting in embryo malformations and thus birth defects.

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The hypothesis will be tested using sensitive assays of the Shh response in the chick embryo. It will be determined if environmental compounds that change the cyclic nucleotide complement of a cell interfere with normal Shh signaling in the developing neural tube in vivo, or in neural explants in vitro. In humans, exposure to the compounds that will be tested is either voluntary, like forskolin, or involuntary, like bacterial enterotoxins, but in either case little is known about their possible adverse effects on early embryos and thus as a cause of birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOSKELETAL EFFECTORS OF ANASTOMOSIS Principal Investigator & Institution: Kolodziej, Peter A.; Assistant Professor; Cell and Developmental Biology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: The development of the respiratory, lymphatic, excretory, and circulatory systems requires the assembly of cells into networks of highly branched tubes. How portions of a tubular network join into a continuous whole (anastomosis) is a poorly understood step in tubular morphogenesis. The proposed study of the structure and function of Drosophila Short Stop (Shot) provides a unique entry into the mechanism of anastomosis, initiates a genetic approach to dissecting this process, and addresses how actin and microtubules are coordinated during morphogenesis, a key issue in cell biology. In shot embryos, tracheal cells undergo normal branching morphogenesis, form a lumen within the segment, but fall to form a lumenal connection spanning the segment boundary. In wild-type embryos, tracheal cells accumulate actin on the side destined to form a lumen. In shot embryos, this polarization occurs in the center of the tracheal network, but not in cells that participate in anastomosis. The expression of a Shot A-GFP fusion in tracheal cells rescues these defects. Shot A contains an N-terminal actin binding domain whose activity may be regulated by the PIP2 phospholipid second messenger, a central rod domain predicted to be 200 nm long, and a C-terminal microtubule binding domain whose activity may be modified by Ca++. Thus, Shot's actin and microtubule binding domains are likely regulated by second messengers and spatially well-separated by a rod domain capable of spanning approximately 10% of the tracheal cell. shot's structure and morphogenetic phenotypes together suggest that the interactions between Shot and the cytoskeleton are dynamically controlled to effect morphogenesis on a 200 nm scale. shot is allelic to kakapo, a gene implicated in integrinmediated cell adhesion, and has human homologs whose functions in development and disease are unknown. To understand the cell biology and biochemical mechanism of anastomosis, we will: l) Define the cytoskeletal changes and cells relevant to anastomosis. 2) Identify key domains in Shot A that are required for anastomosis. 3) Define the role of integrins in anastomosis. These studies will define how Shot effects morphogenesis, define the role of integrin signaling with respect to Shot activity, and will have broad relevance to understanding cell motility and morphogenesis. They will therefore enhance the treatment of abnormalities in angiogenesis and vascular development that occur in cancer and heart disease, and common birth defects such as inappropriate anastomosis of the trachea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEVELOPMENT OF MUSCLE FIBER TYPE IDENTITY Principal Investigator & Institution: Devoto, Stephen H.; Assistant Professor; Biology; Wesleyan University Middletown, Ct 06459

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Birth Defects

Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Our long-term goal is to understand how cell-cell interactions regulate the relative positions and proliferation of distinct muscle cell types during development, an issue of fundamental importance to the understanding of human birth defects, and diseases of muscle including muscular dystrophies and heart disease. We are using zebrafish to study the mechanisms controlling myogenic cell division and differentiation. A large number of zebrafish mutants with abnormal muscle patterning, or with muscle degeneration have recently been identified. These mutants, as well as the established methods for cell transplantations and molecular misexpression, provide powerful tools for understanding the mechanisms of myogenesis. We will test whether the proliferation of muscle precursors and their differentiation into specific fiber types is regulated by a series of inductive interactions from surrounding tissues. 1. We will characterize the role of notochord signaling in regulating the development of fiber type identity. We will define a genetic pathway for slow muscle development. 2. We will test the hypothesis that myogenic precursor cell division is regulated by signals from the notochord, including sonic hedgehog. We will examine the time course of myogenic precursor cell division and test whether myogenic precursor cell division is altered in mutants with impaired midline signaling. We will examine whether specific molecules in the Hh signaling pathway regulate cell proliferation. We will test whether cell proliferation and cell differentiation are linked by examining the effect of disrupting cell division on cell differentiation. 3. We will test the hypothesis that the timing of MRF expression regulates fiber type identity. We will test whether there is a strict correlation between the time of MRF expression and fiber type formed. We will use tissue specific, as well as inducible, promoters to express MRFs in paraxial cells that would normally generate fast muscle fibers, either before or after somite formation, and determine the fiber type these cells develop into. We will test whether forcing MRF expression in segmental plate cells is sufficient to rescue slow muscle development in mutants that are missing slow muscle fibers. 4. We will test the hypothesis that negative BMP4-like signals inhibit the development of specific fiber types. We will block cells from responding to BMP4-type proteins by expressing a dominant negative BMP4 receptor. We will ectopically activate BMP4 signaling by expressing an activated BMP4 receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF OLFACTORY CONNECTIONS Principal Investigator & Institution: Gong, Qizhi; Cell Biology & Human Anatomy; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The main objective of the project is to determine the underlying mechanisms that pattern the mitral cell dendrites in the olfactory system. Formation of precise axonal and dendritic pattern is crucial for establishing functional neural circuitry in the brain. In the olfactory system, the guidance mechanisms of the olfactory sensory neuron axons toward their target have been investigated recently. However, studies are still lacking for the molecular mechanisms of the differentiation and the targeting of the mitral cell dendrites, the postsynaptic partner of the olfactory nerve. We propose to investigate the following hypotheses concerning the control of mitral/tufted cell dendritogenesis: 1) Interaction with olfactory nerve is required for the morphogenesis of mitral/tufted cell dendrites. The influence of the olfactory nerve on mitral cell neurite extension will be tested using in vivo and in vitro approaches. The developmental changes of mitral cell dendrites will be characterized. The orientation of the mitral/tufted cell dendrites will be investigated using 3D collagen matrix. The role

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of the] mature olfactory axons in mitral cell dendritic development will be examined using genetic conditional ablation. 2) Olfactory nerve provides diffusible molecular cues to promote dendritic extension and branching of the mitral/tufted neurons. This hypothesis will be directly tested using dissociated olfactory bulb culture. The presence of the diffusible factors for promoting mitral cell dendritic growth will be examined using olfactory epithelium conditioned medium. Candidate molecules, Semaphorins, neurotrophins and BMPs will be examined for their dendrite growth promoting activity in the dissociated olfactory bulb neuron cultures. Olfactory epithelium derived activity will be characterized by gel filtration and ion exchange chromatography using FPLC. Molecular identity of the OE derived activity will be obtained by peptide sequencing. The long-term goal of our study is to understand the precise cellular and molecular interactions that are critical for the development of the nervous system and to gain insight into the causes of developmental neurological disorder and birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL ANALYSIS OF GENES IN MODEL ORGANISMS Principal Investigator & Institution: Maas, Richard L.; Associate Professor and Chief; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract): Projects 1 and 2 will identify cDNAs encoding transcripts that are disrupted by chromosomal rearrangements associated with specific human birth defects. These experiments will result in the discovery of novel genes and provide circumstantial evidence for the involvement of these genes in the associated birth defects. However, because rearrangements may affect other nearby genes, these experiments will not prove causation. In addition the developmental analysis of human genes is difficult, and the lack of experimentally accessible mutants precludes ordering genes into developmental pathways. Therefore, the strategy that informs Project 3 is to use two model organisms, mouse and Drosophila, to determine whether the genes identified are likely to cause the associated birth defects and to provide insight into their developmental functions. Three specific aims are proposed: (1) to clone and analyze the developmental expression of mouse and fly orthologs of human candidate genes in both wild type and appropriate mutant backgrounds, (2) to determine the map locations of the mouse and fly orthologs and to evaluate whether candidate mutants already exist, and (3) in highly selected cases, when there is not a pre-existing mutation and when the same human developmental phenotype is generated by more than one independent breakpoint, to prepare appropriate mouse and fly models by gene inactivation. Special consideration will be placed on the generation of mutant models for human disorders that affect the development of organs or tissues which are of special interest or for which there is pre-existing expertise in the laboratories of DGAP investigators. To obtain appropriate mouse cDNAs, we will screen embryonic libraries with human cDNAs and search existing EST databases. Both ESTs and the newly available genomic sequence will be used to obtain Drosphila orthologs as either cDNA clones or PCR products of conserved exons, as appropriate. Next, we will perform in situ hybridizations in mouse and fly to determine the developmental expression of the isolated genes. Mouse radiation hybrid panels and the complete Drosphila genomic sequence will be used to map these homologs and to evaluate whether there are existing mutants at the identified loci. Lastly, as appropriate, we will prepare loss-of-function mutations in mouse and fly and analyze the mutant phenotypes. Collectively, these studies have the capacity to delineate the developmental functions of new genes and to provide definitive proof that mutations in specific human genes produce associated

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birth defects. As such, they represent the functional endpoint to a well integrated, functional genomics program project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTHELIN A SIGNALING IN CRANIOFACIAL DEVELOPMENT Principal Investigator & Institution: Clouthier, David E.; Assistant Professor; Anesthesiology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Most bone and cartilage structures of the jaw and throat are derived from cephalic neural crest cells. These cells, arising from the hindbrain, migrate to the pharyngeal arches, where they undergo a proliferation and differentiation program culminating in the formation of craniofacial structures. While numerous signaling cascades regulate this developmental program, the effectors of these cascades are poorly defined. This Independent Scientist Award application requests salary support for the candidate to elucidate the downstream effectors of endothelin-A receptor signaling that control development of cephalic neural crest cells and their derivatives. The candidate will use a variety of techniques to accomplish this aim, including analysis of genomic changes using custom cDNA microarrays and analysis of proteomic changes using 2D-gel electrophoresis and mass spectroscopy. Career goals of the candidate are centered on developing an active research laboratory dedicated to understanding the molecular and cellular basis of normal and abnormal craniofacial development. This lab will serve the additional goal of training pre- and post-doctoral students in craniofacial research. An ISA will enhance the candidate's development as an independent investigator by enabling specific expansion of expertise and research activities. Immediate plans include traveling to an external laboratory to develop expertise in the production and analysis of large-scale custom cDNA microarrays, as well as learning modern techniques in protein profiling and identification at the Core Proteomics Laboratory and the Biomolecular Mass Spectroscopy Core Laboratory, both at the University of Louisville. To take full advantage of the array and proteomic data, the candidate will also attend a bioinformatics course designed to enable researchers to write programs to manage genomic and proteomic research data. The Institution's development plans include: provision of significant start-up funds; guaranteed salary support beyond the period of time requested for K02 support; permission for the candidate to spend essentially fulltime conducting research: minimal departmental duties; funds to travel to laboratories as outlined in the candidate's plans; provision of funds to hire a post-doctoral fellow to contribute to the growing research program in the candidate's laboratory: participation in monthly inter- and intra-departmental discussion groups designed to facilitate the development of the candidate's research program. The research environment offers excellent opportunities for scientific interactions that foster scientific growth and development. Many senior investigators direct active research programs at the University of Louisville, offering many potential interactions. Importantly, the candidate's chairman is a well-established investigator studying the molecular and cellular basis of facial birth defects. Both his personal interaction as well as his continuing efforts to recruit individuals with active research programs in the areas of craniofacial development and genetics underscores the commitment to build a strong research group, further helping the candidate build his own research program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENVIRONMENT & GLI GENES IN NORMAL DEVELOPMENT & DISEASE Principal Investigator & Institution: Iannaccone, Philip M.; Professor; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Developmental pathways are networks of genes which act coordinately to establish the body plan. Disruptions of these genes, which can be associated with environmental exposures, can result in serious dysmorphogenesis or cancer in both children and adults. An important goal of environmental science ought to be reduction of these poor outcomes. This will require an understanding of the genes affected by specific exposures and the consequence of alterations in these genes or their products which in turn will require a complete biochemical understanding of the pathways critical in development. The ligand Sonic hedgehog, the receptors Patched and Smoothened, and the GLI family of transcription factors represent one such pathway critical to the normal development of many organs due to their regulation functions at the nexus of mesenchymal differentiation. Environmental exposure to jervine or UVA and UCB disrupts the pathway. Although some gene targets of the pathway are not known from work in Drosophila key downstream targets and upstream regulators remain to be elucidated in mammals and the roles of these molecules established in normal development in order to better understand their role in dysmorphogenesis and neoplasia. For example, basal cell carcinoma (BCC) is the most common cancer in man and mutations in Patched or over-expression of GLI are both strongly associated with BCC. Prostatic cancer is a serious problem in the US and our preliminary evidence suggests an association of GLI expression with prostatic cancer in humans. We have established a unique team of co- investigators of GLI expression with pro-static cancer in humans. We have established a unique team of co-investigators at Northwestern University who study the regulation and function of the homologues of the GLI genes in C. elegans, Drosophila, mouse, and human. We have previously worked together to collaborate on studies of these genes and these efforts will be greatly enhanced by the current program project allowing use of data from Drosophila and C. elegans in the design of experiments in mouse, or with human material. We are uniquely suited to establish the regulation of the GLI genes at a transcriptional, post- transcriptional, and functional (protein-protein interactions) level. The long term goals of our work will be to determine pathways of development involving GLI genes and their interactions with environmental exposure, in order to establish mechanisms of interact with downstream targets. These experiments will provide data of great significance to both normal development, birth defects, and cancer. The work will very likely provide important general models of transcription factor activity whose utility will extend to a wide variety of developmental, birth defects, and cancer. The work will very likely provide important general models of transcription factor activity whose utility will extend to a wide variety of developmental and cancer problems. Clearly understanding the pathways and the biochemical mechanism of action of developmental genes will be necessary in order to determine the role of environmental exposures on human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITHELIAL/MESENCHYMAL PALATOGENESIS

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Principal Investigator & Institution: Shuler, Charles F.; Professor and Director; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004

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Summary: A critical event in the fusion of the secondary palate is the disappearance of the medial edge epithelium from the midline. Studies in our laboratory have used cell lineage analysis to trace the fate of the medial edge epithelial cells and document that these cells undergo a phenotypic transitions and remain viable as mesenchymal cells. Investigations of the molecular control of the phenotypic transformation have identified TF-beta3 as an important regulating molecule. Homozygous TGF-beta3 knock-out mice do not fuse in organ culture without supplementation of exogenouse TGF-beta3. These findings have led to the hypothesis, TGF-beta3 is a primary effectors molecule responsible for initiating the program of epithelial-mesenchymal transformation in the palatal shelf medial edge epithelial cells during palatal fusion. This hypothesis will be tested by four Specific Aims; 1. To determine the role of TGF-beta3 in the pattern of expression of cell-type specific phenotypic markers in the MEE during palatogenesis; 2. To characterize the mechanism of TGF-beta3 regulation of the cell cycle and MEE cell proliferation prior to palatal shelf contact and the onset of epithelial-mesenchymal transformations; 3. To examine the intracellular signalling pathway in the MEE following binding of the growth factor to its cell surface receptor; 4. To evaluate TGFbeta3 regulation of matrix metalloproteinases in the mesenchyme underlying the MEE responsible for degradation of the basement membrane. Identification of molecular mechanisms essential to the process of palatal fusion will result in future possible applications to determining the mechanisms underlying human craniofacial birth defects, developing prenatal diagnosis strategies, establishing familial risk of craniofacial birth defects, determining the mechanism of action of craniofacial teratogens and reducing the incidence of human craniofacial birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FERTILITY OF DOMINANT NEGATIVE INHIBITION OF FGF IN UTERUS AND OVARIES Principal Investigator & Institution: Koos, Robert D.; Professor; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Successful reproduction requires the cyclical growth differentiation, and death of cells in the ovary and uterus. These complex developmental processes are initiated by gonadotropic hormones from the pituitary and steroids from the ovary, but they are ultimately carried out by locally- produced growth factors. Many of the latter, including the fibroblast growth factors (FGFs), show distinct temporal and spatial patterns of expression in the ovary and uterus during the reproductive cycle or in response to hormonal stimulation. Physical and pharmacological ablation have defined many of the roles of the endocrine hormones in these processes, but those of the growth factors are less amenable to this approach: their roles can only be speculated at based on correlative expression studies. However, new transgenic techniques make it possible to precisely define the functions of FGFs during developmental processes. Studies in this laboratory show that cell-specific targeting of dominant- negative (dom-neg) FGF receptors (FGFRs) in reproductive tissues of transgenic mice is feasible. The goal of this study is to use dom-neg FGFRs, their expression targeted and controlled by cell-specific promoters, to inhibit the actions of FGFs at specific sites and times in the ovary and uterus. The study has four Specific Aims: Aim 1: To identify and localize FGFR subtypes in the mouse ovary and uterus. Aim 2:a) To produce mice that express dom-neg receptors for keratinocyte growth factor (KGF), an epithelial cell-specific FGF, and basic FGF (bFGF) in the epithelial cells of the endometrium using a 404 bp fragment of the uteroglobin promoter; and b) to evaluate uterine function in these mice. Aim 3:a) To

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produce mice that express dom-neg receptors for KGF and bFGF in the granulosa cells of the growing ovarian follicle using the -180 bp fragment of the Muellerian inhibiting substance promoter; and b) to evaluate ovarian function in these mice. Aim 4:a) To produce mice in which the expression of dom-neg FGFRs in the ovary and uterus can be temporarily controlled through tetracycline-responsive regulatory elements; and b) to evaluate the impact on fertility of switching on expression of dom-neg FGFRs in either the ovary or uterus at critical periods in the reproductive process (e.g., during follicular maturation or at the time of implantation). These studies will enhance our understanding of normal reproductive physiology as well as shed light on malfunctions in cell growth and differentiation in the ovary and uterus that lead to infertility, birth defects, and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FETAL ALCOHOL EFFECTS AND IMMUNE DEVELOPMENT Principal Investigator & Institution: Wolcott, Robert M.; Microbiology and Immunology; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-DEC-2002 Summary: (Adapted from the Investigator's Abstract) The teratogenic potential of alcohol is well known and the offspring of mothers who abuse alcohol have been shown to have a broad spectrum of anomalies that have been termed alcohol related birth defects (ARBD). The manifestation of ARB span from reduced birth weight to the unique constellation of features termed fetal alcohol syndrome (FAS). FAS children are the offspring of chronic alcoholic women. However, clinical studies have shown that even moderate drinking during pregnancy can affect fetal development suggesting that alcohol abuse may be one of the leading causes of birth defects. Most studies of the teratogenic effects of alcohol have focused on the morphological and neurological features of the affected infants. However, recent studies have shown ARBD children to be at high risk of having some degree of immune deficiency and consequent increased incidence and severity of infection. Since the immune system is not fully developed at birth the infant's ability to cope with infection is fragile. Therefore, it is important to identify environmental factors that might delay normal immune development and put infants at risk. Recent studies from this laboratory using a murine model of ARBD have shown that in utero exposure to alcohol caused a retarded development of B lymphocytes in fetal liver and neonatal bone marrow and spleen. Phenotypic analysis of developmental intermediates in the B lineage showed several to be affected by in utero alcohol exposure. In particular, the investigator's observed that a previously unreported B cell precursor was decreased in neonatal marrow and spleens of animals exposed in utero to alcohol. In this proposal the applicants will use a model consisting of fetal alcohol exposed and pair-fed and chow-fed control animals to assess the effects of alcohol on B lymphopoiesis during fetal and neonatal life. They will use multiparameter flow cytometry to ascertain the absolute number of B cell intermediates and the phenotype of these cells within the fetal liver and neonatal bone marrow and spleen. The developmental potential of the B cell intermediates will be determined by sorting Blineage cells and other hematopoietic precursors and stem cells and using clonal analysis to determine if alcohol exposure alters the frequency of cells that are capable of differentiation. They will also follow fetal alcohol exposed animals in to adulthood to determine if the exposure affected the function of the humoral immune system and the longevity of the effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FETAL ALCOHOL SYNDROME: GENETIC STUDIES IN ZEBRAFISH Principal Investigator & Institution: Carvan, Michael J.; Assistant Professor; None; University of Wisconsin Milwaukee Box 413, 2200 Kenwood Blvd Milwaukee, Wi 53201 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2003 Summary: This application is being submitted for consideration as a small grant (R03). I am a new investigator planning to expand my research focus to include the area of ethanol-induced birth defects. The long-range goal of this project is to elucidate the molecular mechanisms by which ethanol perturbs embryonic and fetal development and to identify genes that play a role in the sensitivity to ethanol-induced teratogenesis. Fetal Alcohol Syndrome (FAS) is a constellation of congenital anomalies seen in some newborns exposed to alcohol through maternal consumption and is characterized by prenatal and postnatal failure to thrive, central nervous system disorders, and a distinctive set of patterning defects that affect the cardiovascular system, facial structures and limbs. Data from twin studies and animal models argue strongly for a robust genetic component to FAS. Our hypothesis is that mutations in single genes influence one's resistance to ethanol-induced teratogenesis. The zebrafish vertebrate model system has proven to be very powerful for the purpose of identifying genes that play a role in specific physiological events. The specific aims of this proposal are to: [1] Analyze the non-lethal teratogenic effects of ethanol in selected zebrafish strains, and [2] Map and isolate the genomic region(s) containing the gene(s) responsible for the differential sensitivity of zebrafish strains to the embryolethal effects of ethanol exposure. Comparing sensitive and resistant zebrafish strains will elucidate the genetic and molecular mechanisms behind the sensitivity of vertebrate embryos to alcohol toxicity, and may apply directly to alcohol sensitivity in humans. The final products of the project described herein will be a thorough characterization of the nonlethal teratogenic effects of ethanol exposure in zebrafish that are characteristic of FAS, and the identification of several large genomic clones containing candidate genes that influence the sensitivity of zebrafish to the effects of ethanol exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FIDELITY STUDIES OF RB69 DNA POLYMERASE MUTANTS. Principal Investigator & Institution: Bebenek, Anna; Polish Academy of Sciences Warsaw, Poland Warsaw, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Replicative DNA polymerases are the main determinants of the accuracy of DNA replication and thus of the incidence of heritable birth defects and mutation-primed diseases such as cancer. It is therefore of particular interest to us to understand the mechanism by which the main eukaryotic replicative polymerases achieve high fidelity. Bacteriophage RB69 encodes a replicative DNA polymerase with associated 3"-5" proofreading activity. Like T4 DNA polymerase and many polymerases from archaeons, the RB69 DNA polymerase is a member of the B family which includes the eukaryotic DNA polymerases alpha, delta, and epsilon. The availability of crystallographic structures for this polymerase in both the apo for and the replicating complex makes it an excellent model for structure-function studies. Efficient mutation reporter systems are available both in vivo and in vitro to assess the impact on polymerase accuracy of changes in polymerase residues. To conduct fidelity analyses in vivo, we will use a hybrid system in which T4 DNA replication is driven by a RB69 DNA polymerase. T4 whose DNA polymerase has been mutationally inactivated can be replicated by a cognate RB69 DNA polymerase encoded by a recombinant plasmid in

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T4-infected Escherichia coil Mutation frequencies are measured using two T4 reporter systems, reversion at the r/I locus, and forward mutation at the rl locus followed by sequencing. These assays provide rapid and sensitive measurements of the mutational specificities of derivatives of RB69 enzyme. To measure fidelity in vitro, we will use the M13mp2 lacZalpha system. This is a gap-filling assay that measures the accuracy of DNA synthesis across a single stranded gap in bacteriophage M13mp2 RF DNA. The gap contains the mutation-reporter lacZalpha as a template. This system detects specific mispairs, and can support measurements of polymerase processivity the role of accessory proteins. In our fidelity studies we will focus first on the highly conserved thumb-domain motif KKRY which contacts primer-template DNA along the minorgroove and is likely to play an essential role in DNA binding and in accurate, processive DNA replication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF FOREGUT ENDODERM IN CARDIOGENSIS Principal Investigator & Institution: Evans, Todd R.; Professor; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: Cardiovascular malformations are estimated to cause in the US birth defects in 1 percent of children and 10 times as many stillbirths. The primary genetic defects leading to congenital cardiomyopathies are mostly not understood. However, because heart development involves a series of complex tissue movements, fusions, and remodelings, in many cases congenital cardiac abnormalities are thought to arise from defects in morphogenesis during embryonic development. Our long-term goal is to understand the transcriptional regulation of embryonic heart tube morphogenesis. An important but poorly understood process is the formation of the primitive heart tube, that is patterned, along the anterior/posterior axis, leading to programs of chamberspecific gene expression. The myocardium is derived from mesoderm, and recent molecular genetic analyses have therefore focused on the regulation and development of cardiogenic mesoderm. However, embryological and recent genetic experiments indicate that endoderm also plays an important function in regulating cardiogenesis, although the molecular and physiological basis is not known. Current data is consistent with a hypothesis that presumptive and developing foregut endoderm, regulated by GATA transcription factors downstream of retinoid signaling, is critical for proper heart tube patterning and morphogenesis. We propose to use a novel vitamin-A deficient quail model to test this hypothesis, using transplantation experiments and retroviral expression techniques. We will test the function of candidate known and novel endoderm-expressed genes, including those identified in micro-array expression experiments using differentiating GATA-4 deficient murine ES cells. It is anticipated that conserved genetic components of endoderm development will be identified with relevance to heart tube morphogenesis. The specific aims are to: 1. Determine if retinoid signaling is required in foregut for early heart tube morphogenesis. 2. Determine if GATA factor expression is sufficient to rescue foregut development and early heart tube morphogenesis in the absence of retinoid signaling. 3. Identify GATA factor targets expressed in foregut endoderm relevant to heart tube morphogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTION OF NEURAL ACTIVITY IN DEVELOPING RETINA Principal Investigator & Institution: Feller, Marla B.; Biology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Provided by applicant): The mechanisms and function of spontaneous neural activity in the developing mammalian retina will be studied. Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. These "retinal waves" occur during the developmental period when retinal ganglion cell axons are segregating into eye-specific layers in the lateral geniculate nucleus. Experiments using a combination optical imaging, electrophysiology and modeling are proposed to investigate the mechanisms of intercellular coupling that underlie the propagation of retinal waves. In addition, pharmacological manipulations that significantly alter the correlated firing patterns induced by retinal waves and transgenic mice lacking retinal waves will be used to investigate their role in the development of retinal projections to the lateral geniculate nucleus. One result of this work will be to determine the critical parameters of the activity patterns generated by retinal waves for driving activity dependent developmental processes. This work will test the hypothesis that spontaneous, correlated activity is responsible for proper organization of synapses in the developing nervous system and will lead to a further understanding of the cellular and molecular basis for activity-dependent processes in the developing visual system. This work should further our understanding of the organizing principles that govern the normal development of the human nervous system, making it possible to understand the origin of neurological birth defects and to devise strategies that allow the nervous system to regenerate functioning neural circuits after injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF ACTIVINS DURING DEVELOPMENT Principal Investigator & Institution: Matzuk, Martin; Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 17-AUG-1994; Project End 31-MAY-2004 Summary: In mammals, there are approximately 100,000 genes which govern the development of an organism. For development to proceed normally, there must be coordinate interaction of tens of thousands of these gene products in any given cell of the being. Beginning with fertilization, precise expression of these gene products is required during embryonic, fetal, postnatal, and adult development. Aberrant synthesis of even one of these gene products can be disastrous - birth defects, cancer, infertility, and even death are all possible when this developmental program is altered. To fully understand these processes in humans, it is necessary to have physiological models that closely mimic developmental events which occur during the creation of a human being. Toward this end, we have chosen the mouse as the mammalian model for our studies. It is now possible to modify the mouse genome to generate strains of mice with precise genetic mutations. Using this technology, our laboratory has created several models which have birth defects. For example, mice with mutations in the activin betaA and follistatin genes die at birth and have cleft palate, a common birth defect in humans of unknown etiology. In addition, mice a mutations in the activin receptor type II gene have skeletal and facial abnormalities which mimic the human Pierre-Robin syndrome; human newborns with this syndrome have defects in the mandible, leading to respiratory distress which must be surgically corrected immediately. In this grant proposal, we will utilize these previously created mouse models as well as additional models (i.e., mice lacking activins betaC an betaE) to study this complex signal transduction system. The Specific Aims are: 1) Define the functions of the liver-specific TGF-beta-superfamily members, activins betaC and betaE; 2) Perform an activin betaB

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"knockin" to attempt a rescue of activin betaA knockout mice; and 3) Study the postnatal functions of follistatin and activin betaA using inducible knockout systems. Future studies using these mice as in vivo mammalian model systems will enable us to more fully understand the interrelated roles of these proteins in mammalian development and physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER IDENTITY--SEX REASSIGNMENT DUE TO GENITAL DEFECTS Principal Investigator & Institution: Reiner, William G.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from candidate's abstract): This application describes an integrated 5-year training program of didactic study, research mentoring, and research studies focusing on gender identity and psychosexual development in children with major genital birth defects. The long-term objectives include the design of a comprehensive, data-driven, surgical/psychiatric approach to these children's psychosexual development, beginning at birth. Genital malformations are the most common human birth defects, especially those involving the phallic structure. The focus of this project will be children born with such major malformations of the penis that it cannot be reconstructed into a functional penis. The seriousness of these genital defects, thus, traditionally has led to a medical-surgical decision to reassign the sex-of-rearing of these children at birth; that is, 46 XY boys are castrated at birth and surgically reconstructed from male to female and reared as girls. The candidate's extensive experience as a pediatric urologist and now as a child and adolescent psychiatrist working with these children spurred his awareness of the paucity of data on the long-term effects of such sex-reassignment. The specific aims of the research plan are to determine if gender identity formation and psychosexual development are normal in children with genital anomalies severe enough to lead to sex-reassignment male to-female--at birth from the genetic 46 XY sex. The candidate will use validated instruments for gender identity and psychosexual development as well as more general psychiatric interviews. Matched female and male surgical control patients who are not sex-reassigned and matched female and male peer controls will be assessed. In addition, the study will identify the psychosexual developmental obstacles and hurdles the sex- reassigned children and the surgical control children endure. The results of these studies should lead to more rational, research-informed, surgical and psychiatric approaches to these children and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE DISCOVERY FOR CRANIOFACIAL DISORDERS Principal Investigator & Institution: Spritz, Richard A.; Professor and Director; Human Medical Genetics Program; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 18-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Birth defects affect approximately 5% of all infants in the USA, three-fourths involving the head, face, and oral tissues. The most frequent craniofacial birth defects are orofacial clefts: cleft lip +/- cleft palate (CL/P) affects ~1 per 1100 births in the USA, and cleft palate ~1 per 1600 births. Orofacial clefts thus represent a considerable public health problem and expense, and most cases cannot now

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be predicted or prevented. Isolated, "non-syndromic" CL/P (nsCL/P) is the most common craniofacial birth defect, accounting for approximately 70% of all cases of CL/P. nsCL/P is a non-Mendelian, multifactorial disorder, due to multiple genes, each exerting a relatively small effect, interacting with each other and with environmental factors to ultimately result in defective action of specific pathways and genetic networks during fetal craniofacial development. However, few of the genes, and none of the environmental influences, that contribute to nsCL/P are currently known with certainty. The goal of this proposal is to identify the genes, pathways, and genetic networks that are involved in craniofacial development and that thus represent potential targets for genetic and non-genetic determinants of nsCL/P. Identification of these targets will be necessary to devise therapeutic strategies ultimately aimed at preventing this debilitating and disfiguring birth defect. It is currently very difficult to accurately study gene action during craniofacial development in the human. Accordingly, we plan a careful microarray study of gene expression profiles in the developing face of the mouse, in which genetic background (C57BL/6J), careful timing of fetal age, sampling at numerous timepoints, and analyses of many replicate samples can all be readily achieved. In addition, we plan an analogous study of facial development in mice homozygous for a null knockout allele of the Ski locus, carried on the C57BL/6J background. These Ski -/- mice have an exceedingly high rate of midline facial clefts, providing an invaluable comparison of gene expression during aberrant craniofacial development that, in particular, should identify genetic pathways and networks of the developing facies that are responsive to Ski. For genes that appear of particular importance during facial development, we will identify and validate human SNPs for use in future linkage and association studies of nsCL/P. We will apply state-of-art bioinformatics tools to analyze and interpret the data, all of which we will deposit in appropriate public data repositories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE-ENVIORNMENT INTERACTIONS IN FACIAL CLEFTS Principal Investigator & Institution: Christensen, Kaare; Research Professor; University of Southern Denmark Campusvej 55 Odense, Timing: Fiscal Year 2003; Project Start 01-MAR-1998; Project End 31-MAY-2007 Summary: (provided by applicant): Clefts of the lip and/or palate are among the most common and easily diagnosed birth defects, and can provide a model for complex trait analysis. Family and twin studies have clearly indicated a genetic role in the etiology of cleft lip and palate, but environmental components play a major role, as well. The environmental risk factors identified (e.g., medications, alcohol, smoking, nutritional deficiencies) are weak (O.R. < 1.5). Similarly, genetic analysis has not as yet identified any strong single gene as playing a major role in clefting. In the previous funding cycle of this proposal, we were able to analyze a large sample for both case parent triads and case controls for environmental data and molecular analysis. The initial submission took advantage of the cleft population that has been studied in Denmark since the 1930s and which provided an ethnically homogenous population, as well as an extensive historic database to carry out the studies. In this resubmission, we will now partner with parallel efforts underway in Norway, and take advantage of a well-established collaboration between Norway, Denmark and the United States. In addition, we have added a stateof-the-art epidemiologic analytic team based at the National Institutes of Environmental and Health Sciences who are developing new analytic tools to take advantage of the sample sizes available. Finally, advances in molecular technologies--particularly the identification of single nucleotide polymorphisms (SNPs)--have afforded the

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opportunity to carry out genotyping at an unprecedented level for a group of genes which have a high prior probability of being directly involved in clefting. The combination of these unique resources affords the opportunity to study cleft lip and palate in detail. In this project, we will characterize 50 candidate genes and 150 SNP markers within those genes in a total of 600 case parent triads for both isolated cleft palate and cleft lip with or without cleft palate. Positive findings from this initial analysis will then be confirmed in a case control analysis using over 800 cases and 2800 controls. Confirmed findings at this stage will then undergo statistical analysis with an emphasis on gene-gene interaction and, eventually, studies of gene-environment interaction. This project will also set the stage for our use of two large cohort studies taking place in Denmark and Norway in which 200,000 consecutive pregnancies will be ascertained, and detailed epidemiologic, environmental, and biological data made available for studies of clefting. This study will provide a new level of understanding for a complex birth defect trait. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC CRANIOFACIAL DIS

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Principal Investigator & Institution: Lee, Brendan; Associate Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 31-MAY-2006 Summary: Cranial, facial, and limb malformations constitute a significant proportion of the general incidence of birth defects. They may arise from monogenic, polygenic, and/or multi-factorial processes that result from both cell autonomous and cell nonautonomous mechanisms. The frequent co- existence of craniofacial and limb defects in many inherited malformations likely reflects the shared signaling pathways governing their development. The diagnosis, prevention, and treatment of these processes will first require isolation of a cohort of genes which specify the patterning and cell differentiation of these tissues and then correlation of their altered function with phenotypic consequences. Subsequently, the mechanistic bases of their function must be elucidated with respect to each proteins' structure, interaction with other proteins, and interaction with environmental factors. Ultimately, translating the consequences of mutation to phenotype will lead to new diagnostic paradigms. A central cell autonomous process common to many such malformations is transcriptional regulation of osteoblast differentiation and skeletogenesis. Understanding how the master transcription factor, core binding factor alpha (CBFA1), regulates this process and the biochemical and clinical consequences of mutation in this pathway will lead to a framework for understanding the pathogenesis of other malformations affecting skeletal development as well as for diagnosis subtle defects of the cranium and facies. At the same time, cell non-autonomous processes such as vascular hypoperfusion contribute to the genesis of birth defects including 1imb reduction. One of multiple genetic determinants which contribute to the phenotype is loss of function of endothelial nitric oxide synthase (eNOS). Understanding the gene-gene and gene-environmental interactions which impact this phenotype will lead to a better understanding of how we can prevent the consequences of vascular insufficiency on soft and hard tissue development in utero. These mechanistic studies provide platforms for studying the function of genes which cause other malformation syndromes. One approach to rapidly identify gene genes is to generate a large series of dominant mouse phenotypes by both chromosome-specific and genome-wide ENU mutagenesis followed by comparative genomic and phenotypic analysis with well characterized birth defects registries such

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as in the Finnish population. The converse strategy is similarly powerful in rapidly identifying the genes defects registries such as in the Finnish population. The converse strategy is similarly powerful in rapidly identifying the gene defects in phenotypically similar malformation syndromes which suggest alteration of similar or identical developmental pathways. This is the case for hydrolethalus and Meckel syndrome, which are characterized by CNS, craniofacial abnormalities, and polydactyly. They have been mapped to human chromosomes 11 and 17, respectively. Comparative genomic and mouse mutagenesis studies in the syntenic regions will expedite the identification of these genes. Together, these studies will identify genes important in pathogenesis of human malformation and elucidate their modes of action in both cell autonomous and cell non-autonomous models mechanisms of development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS OF MORPHOGENESIS IN A NEMATODE Principal Investigator & Institution: Emmons, Scott W.; Professor; Molecular Genetics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-FEB-1988; Project End 31-JUL-2002 Summary: The aim of this research is to understand how genes determine the morphology of animals. A genetic and molecular approach to this problem is taken using the nematode Caenorhabditis elegans. C elegans is a model organism amenable to genetic analysis that is also useful for developmental biological research because of its fixed cellular anatomy and cell lineages, and because the sequence of its genome is being determined. Many genes identified in model organisms such as C elegans are known to play roles in human disorders such as cancer and birth defects. Study of morphological mutants of C elegans has shown that HOX genes determine the morphology of a set of serially-repeated neuronal structures known as rays. HOX genes, present in all animals, encode conserved homeodomain trascription factors that pattern the anteroposterior body axis as well as other structures such as limbs. How HOX genes help to determine the morphology of rays will be determined by studying the expression of one HOX gene, egl-5, in wild type and in mutants. Regulated expression of egl-5 is necessary for specification of the morphological identities of the rays. Expression of egl-5 will be assayed by means of reporter genes, antibody staining, and in situ RNA hybridization. New mutant screens will be carried out to identify additional genes that regulate the expression of egl-5. The aim is to understand how egl-5 expression is confined to only certain branches of a cell lineage by identifying the factors that regulate its expression. The molecular properties of two additional genes that act along with egl-5 to specify ray identities will be determined by cloning and sequencing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC BASIS OF CLEFT LIP AND PALATE Principal Investigator & Institution: Jiang, Rulang; Assistant Professor; Biology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of the proposed research is to understand the molecular pathogenic mechanisms underlying facial cleft formation. Facial clefts, including cleft lip and cleft palate, are common birth defects that affect approximately 1 in 700 live births worldwide. Individuals with facial clefts undergo extensive surgical, dental, speech and psychological therapies that usually last for many years from infancy through the teenage years. Despite the frequent occurrence and

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extensive medical treatment associated with such birth defects, the causes and the pathogenic processes that lead to cleft lip and/or cleft palate are not well understood. Whereas there is strong evidence for genetic predisposition to facial clefting, attempts at identifying susceptibility loci via family and case control studies have proved inconsistent. This research program has identified a unique animal model for studying the etiology and pathogenic mechanisms of orofacial clefting. Mice homozygous for a spontaneous mutation, Dancer, exhibit cleft lip and cleft palate. Dancer heterozygous mice show predisposition to clefting: these mutant mice show cleft lip after outcrossing to a different genetic background and they also exhibit significantly increase susceptibility to teratogen-induced clefting. Preliminary studies have mapped the Dancer mutation to a 2.2 Mb genomic region, which is syntenic to a human chromosomal region with strong linkage to cleft susceptibility. Thus, the Dancer mutant mice provide a unique opportunity to identify a cleft predisposing gene and to characterize the molecular pathogenic processes, including gene-gene and geneenvironment interactions that lead to orofacial clefting. Two specific aims are proposed for this application: (1) to characterize the molecular basis of the Dancer mutation through a combination of candidate gene analysis and positional cloning; and (2) to characterize the gene expression profiles contributing to cleft pathogenesis in the Dancer mutants using a combination of microarray, real-time quantitative PCR, in situ hybridization and bioinformatic analyses. These studies will greatly increase our understanding of the pathogenic mechanisms underlying orofacial cleft formation and will lead to development of methods for better diagnosis, treatment and/or prevention of orofacial clefting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATTERNING

GENETIC

BASIS

OF

MESENCEPHALIC/METENCEPHALIC

Principal Investigator & Institution: Kessler, Daniel S.; Associate Professor; Anatomy; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 18-JAN-2001; Project End 31-DEC-2004 Summary: (From the Applicant's Abstract): The long-term goal of this research is to understand the genetic basis of development in the mesencephalon (midbrain) and metencephalon (anterior hindbrain) region (MMR) of the brain. Pattern formation throughout the MMR is directed by the coordinated activity of the glycoproteins Wntl and Fgf8, which are secreted by cells within the isthmic organizer (IsO). The IsO is the key signaling center in MMR development yet the molecular mechanism of its action is poorly understood. Two of the most important questions are i) "how are the genes encoding Wntl and FGF8 regulated?" and ii) "what are their distinct roles in IsO patterning?" Fgf8 signaling in known to rely on the transcription factors Enl, En2, Pax2 and Pax5 and at least part of their function is to participate in an autoregulatory loop. Understanding whether they govern Wntl expression independent of Fgf8 is crucial but unknown. In contrast, our research identified a unique transcription factor, Lmxlb, as being a key regulator of Wntl, and suggested that neither Wntl nor Lmxlb are part of the proposed Fgf8/Pax/En autoregulatory pathway. Nevertheless, some form of interplay exists between these signaling pathways because Wntl and Fgf8 expression are codependent. We propose to perform genetic experiments using both chick and zebrafish model systems to dissect the mechanisms that govern Wntl and Fgf8 expression. Our specific aims are: 1. To determine whether Lmxlb/Wntl activity ever impinges on En/Pax/Fgf8 expression. 2. To determine whether Pax2 or Pax5 ever i) directly maintain the Lmxlb/Wntl pathway or ii) act as cofactors for Lmxlb maintenance

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Birth Defects

of Wntl. 3. To determine whether Enl or En2 directly maintain the Lmxlb/Wntl pathway. These studies should allow us to construct a model describing the coordinate regulation of Wntl and Fgf8. This should give insight into how early mammalian development occurs and eventually suggest means of preventing or treating human birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC CONTROL OF THE YEAST SPORULATION PROGRAM Principal Investigator & Institution: Herskowitz, Ira; Professor; Biochemistry and Biophysics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The long-term goal of this project is to understand the molecular mechanisms that program the events of yeast sporulation -- the process by which yeast forms gametes. This process begins with a diploid vegetative cell and yields an ascus containing four haploid meiotic products derived from that cell. Because the steps of yeast meiosis are like those of higher eukaryotes, it is expected that the mechanisms and machinery used in yeast may shed light on meiosis in higher organisms and thus provide insights into the molecular basis of infertility and birth defects in humans. Prior studies by others led to the hypothesis that the events of sporulation are determined by a transcriptional cascade involving sequential transcription of early, middle, and late genes. Prior studies by others also identified what appears to be a key decision-making point at pachytene, after replication and recombination but before the first meiotic division, which monitors completion of recombination. We have recently identified the regulatory protein, Ndt80p, that governs transcription of many of the middle sporulation genes and proposed that it may play a central role in the decision of cells to initiate meiotic divisions after completion of replication and recombination. In addition, we have carried out whole-genome expression studies using DNA microarrays which reveal that Ndt80p controls transcription of more than 150 genes during sporulation. The goal of this proposal is to determine how the program of sporulation is controlled using Ndt80p as a jumping off point. In particular, these studies seek to understand how Ndt80p synthesis and activity are regulated and how it functions to activate transcription of a large group of genes involved in chromosome segregation and spore morphogenesis. Learning about Ndt80 protein is likely to yield enormous insight on the decision to exit meiotic prophase and on the overall program of sporulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS GASTRULATION

OF

MORPHOGENESIS

OF

VERTEBRATE

Principal Investigator & Institution: Kane, Donald A.; Assistant Professor; Biology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: How do the cells of the gastrula move to form an embryo? The long term objective of the proposed work is to understand the genetic and biomechanical basis for gastrulation in a model vertebrate, the zebrafish. The zebrafish processes unique optical and genetic properties that make it ideal for these studies. Moreover, the recent isolation of zebrafish mutants that are deficient in cell motility have identified many of the genes necessary for cell motility. The gene half baked (hab) is essential for the process of epiboly, the vegetalwards spreading of the blastoderm to cover the large yolk cell. This

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process is the first morphogenetic movement of the zebrafish gastrula and is similar in principle to the pregastrulation spreading movements in Xenopus and mouse. Mutations in hab arrest epiboly. Furthermore, hab possesses a maternal- zygotic dominant effect phenotype, an unique genetic interaction, indicating that hab is necessary both maternally and zygotically. Understanding the early role of hab will be crucial for our understanding of cell motility in the early embryo and the zygotic and maternal controls on this motility. The specific objectives of this proposal are aimed at understanding the zygotic and maternal roles of hab in the zebrafish gastrula, and at establishing the molecular nature of hab. The gene hab is necessary for the blastoderm to participate in epiboly. The generally accepted hypothesis for teleost epiboly is that the yolk cell tows the blastoderm toward the vegetal pole. Several lines of evidence argue that hab may acting in the blastoderm, challenging this simple towing hypothesis. The specific aims of this proposal are: l) to identify the molecular nature of hab, 2) to delineate the maternal affect phenotype of hab by creating germline chimerae, 3) to complete the cellular characterization of hab, testing the towing hypothesis of epiboly by locating the site of action of hab using cell transplantation, 4) to assay the interactions between hab and the gene spadetail, a gene that also necessary for cell motility of the deep cells of the blastoderm. Achieving these objectives will lead to an understanding of hab gene function as well as a detailed understanding of the morphogenetic movement of epiboly. Such an understanding will have broad application, not only to the study of teleost embryology but to birth defects in humans and the spreading of cells in metastasizing cancers. Furthermore, this work will lead to a fresh new view of cell motility in vertebrate embryology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTOR SIGNALING IN MOUSE PALATOGENESIS Principal Investigator & Institution: Chen, Yiping; Associate Professor; Cellular and Molecular Biology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Cleft palate is one of the most common birth defects in human. Mammalian palatogenesis is a complex and multiple step process, largely depending on the sequential and reciprocal interactions between apposed epithelial and mesenchymal tissues involving diffusible growth factors and homeobox genes. Genetic or environmental interruption at any step of this complex process can result in cleft palate. Bone Morphogenetic proteins (BMPs), Sonic hedgehog (Shh), and Fibroblast Growth Factors (FGFs) have been implicated in the formation of many vertebrate organs. However, their potential role in mammalian palatogenesis remains unknown. Our previous studies demonstrated that Msx1 homeobox gene, mutations, which are associated with non-syndromic cleft palate and tooth agenesis in human, control a genetic hierarchy involving BMPs and Shh in the regulation of outgrowth of the anterior portion of the secondary palatal shelves. In the anterior portion of developing palatal shelves, the expression of Bmp4, which is regulated by Msx1 in the mesenchyme, maintains Shh expression in the medial edge epithelium (MEE). Expression of Shh in the MEE is required for the growth of palatal shelves via activation of Bmp2 in palatal mesenchyme. Our preliminary studies also demonstrated a restricted expression of FGFR2 in the posterior palatal mesenchyme, which can respond to FGF signal in terms of gene expression, suggesting that FGF signaling may regulate the development of the posterior portion of the palate. In this application, three specific aims are proposed to further test the regulation and function of the BMP-Shh pathway in anterior palatal development, and to establish a role for FGF signaling in the regulation of posterior

34

Birth Defects

palate development. Aim 1 is designed to examine the regulatory mechanism of Shh expression in the MEE by mesenchymal BMP4. The specific type I BMP receptor that is involved in this regulation will also be determined. Transgenic mice will be generated that carry either a dominant-negative BMP receptor-IA transgene driven by the K14 promoter or a constitutively active BMP receptor-IA transgene driven by the Msx1 promoter. In Aim 2, the role of Shh in palate formation will be defined by analyzing Shh conditional knockout mice and transgenic mice overexpressing Shh in the palatal epithelium. It will also test whether ectopic Shh expression in the palatal epithelium of the Msx1 mutants can bypass the requirement for both Msx1 and BMP4 in palatal mesenchyme to restore cell proliferation and rescue cleft palate. Lastly, in Aim 3, the role for FGF signaling in palatogenesis will be established by testing FGF's function in the regulation of cell proliferation and survival in vitro by organ culture, and in vivo by analyzing Fgf10 knockout mice that exhibit a cleft palate. Our long-term goal is to unveil the molecular mechanisms of mammalian palatogenesis and cleft palate formation, which would provide insight for genetic prevention and therapy for human cleft palate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEALTH IMPACT OF CONGENITAL CYTOMEGALOVIRUS INFECTION Principal Investigator & Institution: Dekker, Cornelia L.; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant) Human HCMV infection is the leading infectious cause of congenital birth defects and causes important morbidity and mortality in immunocompromised patients of all ages. Humans are the only reservoir for this infection and many unique strains circulate in the general population throughout the world. Rates of congenital HCMV infection in the U.S. range from 0.2 percent to 2.2 percent of all live births, affecting approximately 10,000 to 80,000 infants born each year. The Institute of Medicine study of vaccine objectives has therefore identified congenital HCMV prevention by vaccines as a Level I priority. The overall objective of this application is to define the epidemiology and disease burden of congenital infection caused by HCMV in a diverse, Northern California population by virologically screening 20,000 newborns from three area hospitals over a two-year period. In Specific Aim 1, screening will be done using a direct early antigen detection of fluorescent foci (DEAFF) method to identify HCMV in saliva samples of newborns. We hypothesize that incidence in white infants will be different than that for Hispanic and Asian/Pacific Islander infants born in this area. Virus isolates obtained from infected infants will be tested to determine genetic relatedness and whether specific subtypes are associated with the occurrence of symptomatic vs. asymptomatic infection of the infant. To assess disease burden, we will describe clinical features in infected infants and determine the distribution of symptomatic vs. asymptomatic presentation among demographic groups. In Specific Aim 2, we will describe the incidence, severity and timing of sensorineurat hearing loss (SNHL) over three years in infected infants, and determine whether universal newborn hearing screening identifies SNHL caused by congenital HCMV. The pattern of hearing loss will be described for the cohort, and affected infants will be offered remedial treatment. In Specific Aim 3, we will describe the HCMVspecific CD4 and CD8 T cell responses of the infected cohort over three years and determine whether there are differences in immune response pattern between symptomatically and asymptomatically infected infants, and between infants and

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adults. Data from this study will help to define target populations for immunization and clinically relevant immune responses for vaccine researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HERPESVIRUS PROTEIN SYNTHESIS AND VIRION ASSEMBLY Principal Investigator & Institution: Gibson, Wade; Professor; Pharmacol & Molecular Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-SEP-1977; Project End 31-MAY-2006 Summary: (provided by applicant): The long-term goal of this research is to learn more about the structure and function of herpesvirus proteins, and translate that information to new diagnostic, preventive, and therapeutic strategies for dealing with CMV-related diseases of man. We use cytomegalovirus (CMV) as our model system because of its medical relevance to immunosuppresion resulting from AIDS, organ transplantation, and cancer chemotherapy, and to sexually transmitted diseases and birth defects. Additionally, there is a need to determine the molecular similarities and differences between herpes group viruses in order to understand their biological differences. Our more immediate objectives are to study the synthesis, structure, and function of specific viral proteins that are essential for virus replication, with a concentration on those involved in virus assembly. Our rationale for studying virus structure and assembly is that most aspects of virus replication are directly or indirectly coupled to the assembly process; therefore, it ultimately represents a major and largely untapped source of new targets for antivirals. The specific aims of the work proposed here are to uncover processes that modulate the very early and intermediate stages of CMV assembly. We will continue our studies of how the proteins of the capsid interact and why, and what modifications they undergo and how these govern the process of capsid formation and maturation. Our plans also include studying three of the tegument proteins that appear to be most closely associated with the capsid and which may anker other tegument or envelope proteins to the capsid, or perhaps help the capsid negotiate the nuclear membrane as it exits or target it after entry. We will apply a combination of biochemical, cryo-EM/imaging, and genetic experiments to bear on these questions, including (i) use of a recently developed in vitro binding system to study capsid/tegument interactions, and (ii) use of the HCMV-bacterial artificial chromosome system to produce mutant viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE PROTECTION AGAINST MNU-INDUCTED DIGITAL DEFECTS Principal Investigator & Institution: Prater, M R.; Biomedical Scis/Pathobiology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Provided by applicant): Dr. Renee Prater has completed her D.V.M., M.S. in physiology, residency in clinical pathology, and is a Ph.D. candidate in toxicology with an expected completion date of 12/2001. She is a highly motivated scientist who sees this award as an opportunity to advance her research career as an independent primary investigator in developmental immunotoxicology. The proposed research will investigate mechanisms by which maternal immune stimulation prevents methylnitrosourea (MNU)-induced birth defects. MNU's teratogenic effects are dosespecific and dependent upon the time of exposure in relation to gestational age. Organ systems affected by MNU include the central nervous, lymphoid, digestive,

36

Birth Defects

genitourinary, and limbs. Data from the laboratory have demonstrated that nonspecific activation of the murine maternal immune system can dramatically reduce several chemical-induced birth defects, including MNU-induced digital defects (DDs), and that maternal immune stimulation normalizes teratogen-altered expression of fetal regulatory genes in palatal development. Other investigators have reported that altered gene expression in MNU-induced teratogenesis can be normalized with dietary antioxidant supplementation (Hulten et al. 1998). A focused examination of altered gene expression and protection from MNU-induced DD is now logical. Specifically, the following hypotheses will be tested: 1) MNU affects gene expression regulating digital development; 2) maternal immune stimulation normalizes gene expression through regulatory proteins secreted by activated immune cells, and 3) protection from MNUinduced digital defects can also result from dietary supplementation with the antioxidant butylated hydroxytoluene (BHT) in a process involving similar effects on regulatory genes. These studies are expected to significantly increase our understanding of genetic mechanisms by which maternal immune modulation reduces this specific birth defect. Clearly, this research is of importance to human health, as determining the mechanisms will improve the understanding of this disorder and contribute to means for prevention or cure. This research under the guidance of Drs. Steven Holladay and Eric Wong at Virginia Tech. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISTIC ANALYSIS OF MICROTUBULE-BASED MOTORS Principal Investigator & Institution: Gilbert, Susan P.; Associate Professor; Biological Sciences; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The long term goal is to establish the structural and mechanistic basis for force production by kinesin superfamily members. The proposed studies reflect a longstanding interest in intracellular transport and a commitment to biomedical research. The specific aims of this research proposal are to establish the kinetic and thermodynamic basis of force generation of the EgS and Kar3 ATPases in direct comparison to Ncd and conventional kinesin. All use ATP to drive unidirectional microtubule based movements. Ncd, Eg5, and Kar3 are involved in spindle dynamics during meiosis and/or mitosis and therefore are required for proper chromosome segregation. In contrast, kinesin is a neuronal motor that promotes movement of membranous organelles. Kinesins motility is distinctive because of its processivity. Ncd, Kar3 and Eg5 are believed not to be processive. Both Ncd and Kar3 promote minus end directed microtubule movements, yet kinesin and Eg5 promote plus end directed movements. Furthermore, Kar3 as a monomer exhibits unidirectional movement; therefore, Kar3 is an interesting motor to study in direct comparison to the climeric kinesins kinesin, Eg5, Ncd. The results with Ncd and kinesin indicate that both motor domains of the dimer are required for movement. Eg5 is also dimeric, yet evidence to date indicates it is not processive. The studies with EgS, in direct comparison to Ncd and kinesin, are intended to define the mechanistic features required specifically for processivity that may be distinct from those features that drive plus end directed movements. In addition, the experiments with mutant kinesin motors will explore aspects of the ATPase crossbridge cycle that are not accessible by studying the wildtype motor. The proposed experiments will evaluate the mechanistic features that spindle motors have in common, and at the same time address specific questions about energy transduction for dimeric motors in comparison to monomeric motors. A comprehensive analysis of these 4 molecular motors will provide information to begin to understand

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the structural and mechanistic requirements for the diverse movements occurring during the cell cycle and during neuromuscular development and function where genetic alteration can result in birth defects, degenerative diseases, and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEIOTIC INTERACTIONS OF THE RECA HOMOLOGUE DMC1 Principal Investigator & Institution: Bishop, Douglas K.; Assistant Professor; Radiation & Cellular Oncology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-MAR-2007 Summary: (provided by applicant): Homologous recombination occurs at high frequency during meiosis and plays a critical role in promoting reductional segregation of chromosomes. Meiotic recombination is initiated by the programmed induction of DNA double strand breaks (DSBs) and involves a mechanism related to recombinational repair of DNA damage in mitotic cells. Defects in meiotic recombination cause chromosome non-disjunction and loss, both of which lead to birth defects and spontaneous abortion. Failure of recombinational repair in mitosis is implicated in the etiology of breast cancer and other malignancies. The central step of recombination is homologous strand invasion, a process promoted by proteins called recombinases. In order to promote strand invasion, recombinases must first form filaments on regions of single stranded DNA. This assembly process is regulated by recombinase accessory factors. During meiosis in the budding yeast S. cerevisiae, strand invasion is promoted by two structural and functional homologs of the E. coli recombinase RecA. These two are Rad51, which also promotes recombinational repair in mitosis, and Dmc1, which is meiosis-specific. The two recombinases, while capable of acting alone, often cooperate at sites of recombination. The proposed experiments seek to elucidate the mechanisms underlying recombinase cooperation before and during the strand invasion stage and to determine how those mechanisms regulate the outcome of recombination. The specific aims of the proposal include: 1. Biochemical characterization of interactions between Dmc1, the single strand DNA binding protein RPA, and several proteins known to be accessory factors for Rad51-mediated strand invasion. This aim will test the hypothesis that assembly of Dmc1 is regulated by a manner distinct from that regulating assembly of Rad51. 2. To examine the genetic requirements for specific association of Rad51 and Dmc1 at sites of recombination in living cells. 3. To test the hypothesis that Rad51 and Dmc1 assemble on opposite DNA ends created by a DSB and do so via a concerted mechanism. 4. To determine if meiotic functions constrain the strand invasion activity of a DNA end created by a DNA double strand break relative to its partner end. 5. To use a novel genomics approach to identify proteins that interact with Dmc1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEIOTIC TELEMERE CLUSTERING IN FISSION YEAST Principal Investigator & Institution: Cande, W Z.; Molecular and Cell Biology; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The close relationship between the timing of telomere clustering and initiation of chromosome pairing during meiotic prophase has led to the suggestion that the bouquet like arrangement of telomeres on the Nuclear Envelope (NE) is a key step in the homology search. It is our goal to describe the mechanism of bouquet formation and the molecules needed to bring it about. Fission yeast has a prominent bouquet that persists throughout meiotic prophase, a limited

38

Birth Defects

number of chromosomes (1n=3), and the telomeres cluster on the NE in association with the Spindle Pole Body (SPB). These characteristics make Schizosaccharomyces pombe an ideal organism to investigate the mechanism of bouquet formation by molecular, genetic and cytological approaches. In a pilot genetic screen, we have isolated meiotic mutants that have defective organization of telomeres (dot). We may have mutants in two potential members of the telomere attachment complex, Spo3, a transmembrane protein, and dot5, a gene required for heterochromatin association with the NE. To test this idea, we will clone dot5, use cytological approaches to localize Spo3 and Dot5 proteins in the nucleus during the bouquet stage, and study their behavior in living cells as telomeres cluster and in fixed cells at an ultrastructural level, and use biochemical and molecular approaches to identify interacting proteins. Finally, we will initiate a new genetics screen based on the cytology of dot phenotypes and insertional mutagenesis, to identify other components of the complex. We will use dot mutants such as dot5 and dot 4-550 that are defective in karyogamy to determine whether SPBs fuse together at karyogamy and whether karyogamy is required to maintain the bouquet. Dot2 is deficient in karyogamy and bouquet maintenance because it has multiple miniSPBs. We will determine whether the dot2 phenotype is due to overexpression of SPB proteins. Finally, we will investigate telomere clustering in living cells using deconvolution light microscopy and mutants to dissect function. This kinetic analysis will allow us to distinguish between various models of telomere clustering. Since meiosis is an evolutionarily conserved process, what we learn about the bouquet stage in fission yeast should be applicable to other eukaryotes, such as human, where problems in meiotic prophase lead to chromosome missegregation, aneuploidy, birth defects or aborted fetuses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METOTIC SPINDLE ASSEMBLY AND ANEUPLOIDY IN MAMMALS Principal Investigator & Institution: Compton, Duane A.; Associate Professor; Biochemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): It has been estimated that 15-20 percent of all human conceptions are chromosomally abnormal (aneuploid), and that many of these abnormalities occur because of errors in chromosome segregation during female meiosis. One of the strongest predictors of aneuploidy is maternal age with nearly half of all oocytes ovulated in women over age 40 containing errors in chromosome number. Most aneuploid conceptions die before birth, but several specific aneuploid states (e.g. trisomy 21) are viable and, as a class, represent the most common cause of mental retardation in man. Despite this clinical importance, very little is known about the cause of chromosome nondisjunction during female meiosis or why the rate of non-disjunction increases with maternal age. One model proposed to explain the correlation between maternal age and frequency of chromosome nondisjunction suggests that the efficiency of folliculogenesis (the development of the oocyte within the follicle in the ovary) is reduced in older women. We hypothesize that reduced or impaired folliculogenesis could contribute to chromosome non-disjunction by reducing the quantities of specific microtubule motor proteins necessary for alignment and/or segregation of chromosomes on the meiotic spindle. To test this hypothesis, we propose to use transgenic mouse technology to specifically perturb the function of the kinesin-related proteins Kid and MCAK during female meiosis. We are targeting Kid and MCAK because they are not necessary for overall spindle assembly, but are required for efficient chromosome alignment and/or segregation during mitosis and, in some non-

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mammalian systems, meiosis. We will specifically perturb the function of Kid or MCAK during female meiosis by transgenic expression of anti-sense or dominant negative constructs using a mouse oocyte-speciflc promoter. We will evaluate the consequences of disrupted motor function during female meiosis by examining the fertility of transgenic females, the frequency and type of birth defects in pups born from transgenic females, and the alignment of chromosomes on meiotic spindles in oocytes from transgenic females. Successful completion of these experiments will validate the application of transgenic mouse technology to study the mechanisms of spindle assembly during female meiosis in mammals and could increase our understanding of the etiology of disorders such as Down?s Syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ANALYSIS OF BRAIN DEVELOPMENT Principal Investigator & Institution: Callaerts, Patrick F.; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-MAR-2005 Summary: (provided by applicant): A fundamental problem in neurobiology concerns the generation and maintenance of neuronal identity as determined by morphology, connectivity, adhesive properties, neurotransmitter phenotype, and membrane excitability. These properties are established and maintained through the action of transcription factors. Despite significant advances in the characterization of transcription factors and of genes encoding effector molecules, the relationship between transcription factors and the expression of effector molecules that direct neuronal morphogenesis or later aspects of the neuronal phenotype such as specialized synaptic signaling properties and neurotransmitter phenotype, remains largely undefined. Here, we propose to study the role of the Drosophila Pax-6 homolog eyeless in postmitotic mushroom body neuron differentiation to provide better insights into the mechanisms by which transcription factors drive expression of neuronal traits and determine neuronal specificity. To this end, we will detail the phenotypes of postmitotic mushroom body neurons, and study the gene regulatory network controlled by eyeless. Specifically we will pursue the following specific aims. (1) Determine when eyeless is required during mushroom body development, and analyze the mushroom body defects observed in eyeless mutants. (2) Identify cis-regulatory elements required for mushroom body-specific gene expression. (3) Initiate the characterization of a putative target gene. The proposed research is essential for understanding how the cellular properties of mushroom body neurons are established by the gene regulatory network controlled by eyeless, as a prerequisite to understanding mushroom body-mediated behavior namely learning and memory and locomotion control. Furthermore, the remarkable conservation of the Pax-6 genes implies that analyzing Pax-6/eyeless function in the Drosophila brain will help explain the congenital brain defects observed in human PAX6 mutants. In addition, fundamental insights into neuronal gene regulatory networks will be important to understanding the many brain-related birth defects in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR DETERMINANTS OF DEVELOPMENTAL DEFECTS Principal Investigator & Institution: Greene, Robert M.; Professor; Mol/Cell/Craniofacial Biology; University of Louisville University of Louisville Louisville, Ky 40292

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Birth Defects

Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The purpose of this application for a Center of Biomedical Research Excellence (COBRE) is to foster health-related research and increase the competitiveness of junior, unfunded investigators at the Birth Defects Center at the UL School of Dentistry for independent funding. If funded, this COBRE will augment and strengthen the biomedical research capacity at the Birth Defects Center through provision of flexible support to expand and develop biomedical faculty research capability. The program is led by an established biomedical research scientist, well recognized for his extensive expertise central to the research theme of the proposal. The application seeks support for junior investigators from several complementary disciplines, each of whom will be mentored by an established, well-funded senior biomedical research faculty member, recognized for his/her scientific expertise in the area of the junior investigator's research proposal. This approach is a critical assurance of success of this initiative. This application represents an integrated series of studies focusing on two common themes - molecular mechanisms of birth defects and cellular signal transduction - that encompass a number of diverse scientific disciplines. Faculty from three different departments in the Schools of Dentistry and Medicine, representing a multiplicity of scientific disciplines, present a multifunctional approach to questions of the molecular basis of developmental anomalies. This application, if funded, will substantially enhance the development of five young investigators with outstanding potential to develop into competitive, independent and collaborative investigators. A detailed plan for their research career development has been formulated, expectations and goals for achieving extramural support is outlined, the extent of departmental and university support provided to these junior faculty is substantial, clear and tangible evidence of institutional commitment has been documented, and sufficient and adequate space and equipment resources for the conduct of the proposed studies exists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FORMATION

MOLECULAR

MECHANISM

OF

PARAXIAL

MESODERM

Principal Investigator & Institution: Chapman, Deborah L.; Biological Sciences; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The developing mesoderm of the vertebrate embryo is subdivided into four populations each giving rise to different tissues and organs; the paraxial mesoderm gives rise to the somites. The transcription factor, Tbx6, is absolutely required for the development of the posterior paraxial mesoderm: in Tbx6 mutants the posterior somites are replaced by ectopic neural tubes. The primary aim of this project is to provide a more detailed picture of the molecular mechanisms operating in the formation of paraxial mesoderm and will use the Tbx6 gene as the primary tool to uncover the factors directing paraxial mesoderm formation and specification. The specific aims are: (I) To use transgenics and comparative genomics to identify and characterize the cis-regulatory regions directing Tbx6 expression during embryogenesis. (II) To test the ability of candidate transcription factors to bind to the regulatory regions of Tbx6. The prime candidates are LEF-1/TCF1, which function through the secreted signaling molecule Wnt-3a, and RBP-JK, which functions in the Notch signaling pathway. (Ill) To identify the DNA binding site of Thx6 and to test the ability of Tbx6 to bind to the regulatory regions of candidate downstream targets. (IV) To develop a fate map of Tbx6 expressing cells in both normal and mutant backgrounds. These studies will not only help us to understand the function of Thx6 in anterior somite formation

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41

but also the fate of Tbx6 expressing cells in various mutant backgrounds, including T. The somites are crucial components of the vertebrate body plan but a fuller understanding of the molecular events required for their development will be of more than mere academic interest. Such knowledge may provide insight into the cause of different types of birth defects and in the future may greatly assist attempts to direct the development of stem cells to produce specific types of tissues for transplants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATTERNING

MOLECULAR

MECHANISMS

OF

CEREBRAL

CORTICAL

Principal Investigator & Institution: Grove, Elizabeth A.; Associate Professor; Pharmacological & Physiol Scis; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 25-FEB-2002; Project End 31-JAN-2006 Summary: (provided by applicant): The broad goal of this research is to identify the mechanisms that generate the area map of the mammalian cerebral cortex. Using the innovative method of in utero electroporation in living mouse embryos we have found evidence that the signaling molecule FGF8 specifies positional identity in the neocortex from a source in the anterior telencephalon. Modifying the endogenous anterior FGF8 signal shifts areas along the anterior/posterior (A/P) axis of the neocortex, and introducing a new posterior source of FGF8 elicits a partial area duplication with the formation of ectopic somatosensory barrel fields. The first aim of these studies is to determine if FGF8 can act as a master signal that regulates the patterning and differentiation of the cortical area map along the A/P axis. Experiments will utilize in utero electroporation to manipulate FGF8 signaling, and the area map will be analyzed postnatally when neocortical areas are identifiable by classic connectional and cytoarchitectonic criteria. The second aim is to test the hypothesis that the anterior FGF8 source interacts with a second source of signaling proteins, the cortical hem, proposed to regulate cortical patterning along the medial/lateral axis. Such an interaction would promote coordination of patterning along the two major axes of the cerebral cortex. The third aim is to clarify the FGF signaling mechanism that patterns the cortical primordium. Using electroporation of FOF and FGF receptor constructs, we will determine which FGF family members, in addition to FGF8, may constitute the endogenous patterning signal, which receptors mediate the signal, and whether the FGF signal acts to pattern the cortical primordium directly or via a relay mechanism. Finally, we will attempt to identify molecular mechanisms that lie downstream of FGF signaling in area patterning. In particular, to analyze the relation between FGF8 and the transcription factor Emx2, also implicated in A/P cortical patterning, we will employ electroporation-mediated gene transfer into a mouse line lacking Emx2 function. Several human birth defects that involve skeletal and CNS abnormalities have been traced to mutations in the FGF receptor FGFR3, which encodes a high-affinity FGF8 receptor. In particular, these mutations lead to hitherto unexplained defects of cerebral cortical development. The focus of the proposed studies on FGF8 and FGFR3 signaling in early cortical patterning should clarify how these defects are generated. More generally, an understanding of the molecular mechanisms that pattern the cerebral cortex should shed light on genetic disorders that lead to malformation and mispatterning of this part of the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Birth Defects

•

Project Title: MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT Principal Investigator & Institution: Kimelman, David; Biochemistry; University of Washington Seattle, Wa 98195

Associate

Professor;

Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-JUL-2004 Summary: The Wnt pathway has emerged as a critical regulator of early axis specification in vertebrates. This proposal aims to determine how the Wnt pathway becomes activated in the early embryo, and how this leads to the induction of the Spemann organizer. In Xenopus, the Wnt pathway is activated by a sperm-induced rotation of the embryonic cortex. This activation does not require Wnt ligands, and may therefore be regulated intracellularly. Following the earlier discovery that a key event in Wnt- signalling is inhibition of the kinase GSK-3, this laboratory has recently identified a novel, inhibitory GSK-3 binding protein, GBP, and demonstrated that it is required for dorsal axis induction. A major aim of this proposal is to determine precisely how GBP inhibits the activity of GSK-3, which functions as part of a multi-protein complex. Since GBP may be localized or activated locally in response to cortical rotation, investigations will determine where GBP is found in the embryo, whether it is regionally modified, and whether it binds other proteins in the early Xenopus embryo. Additional studies will ask whether the regulation of Wnt signalling by GBP is used throughout development, or whether GBP is solely a specialized maternal regulator of the Wnt pathway used only for dorsal axis specification. A second major area will investigate specifically how the activation of the Spemann organizer is regulated. Since the organizer forms in response to a Wnt pathway-mediated transcriptional depression, the molecular basis of this depression will be investigated. Furthermore, the factors that restrict the formation of the organizer to the equator of the embryo will be investigated since the principle role of the cortical rotation is to ensure that the Wnt pathway is activated at the equator. Since the Wnt pathway is implicated in normal vertebrate development and oncogenesis, these studies will be important in understanding the molecular basis of birth defects and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR STUDIES IN NONSYNDROMIC CLEFT LIP AND PALATE Principal Investigator & Institution: Hecht, Jacqueline T.; Professor; Pediatrics; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: (Adapted from investigator's Abstract): The specific aim of the investigations described in this proposal is to define molecular mechanisms that cause, or predispose, to non-syndromic cleft lip with/without cleft palate (NSCLP). NSCLP is one of the most common birth defects with a prevalence of approximately 1 in 1000 live births. The etiology of this disorder has been unclear although recently there is evidence of genetic etiology. The applicant has reported evidence of linkage between familial NSCLP and BCL3 gene on chromosome 19 in 17 of 39 families, and states that she is in a unique position to accomplish the goals because her lab has characterized 60 families with NSCLP, the technology for genomic mapping is now mature, and that a number of biologically relevant candidate genes have been identified. The current application describes experiments aimed at identification of new multiplex and simples families with NSCLP, and to map genetic loci causing NSCLP using both candidate gene approaches and a genome wide approach with the Weber-CHLC screening set of PCR based markers (version 8). The plan is to study at least 42 candidate genes that may

Studies

43

possibly have a role in craniofacial embryogenesis as well as random gnomic markers. Both non-perimetria and perimetria statistical methods will be used to optimize linkage detection and markers of candidate genes are to be identified. Family studies will be tested to confirm or exclude linkage in two ethnically diverse populations. One of the aims is to follow up on prior data in which 17 families were linked to the BCL locus by performing mutation analysis at BCL3 in the subset of families with evidence of linkage with cleft lip and palate to BCL3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER PROSTHETICS

TRIAL

OF

CPE

FOR

MAXILLOFACIAL

Principal Investigator & Institution: Gettleman, Lawrence M.; Professor; Diag Sci,Prosthodon, Gen Dent; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2003; Project Start 21-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Maxillofacial prosthetics is a subspecialty of prosthodontics, providing the clinical rehabilitation treatment of patients who have lost parts of the face due to cancer, trauma, or birth defects. It is an orphan field, a) offering fundamental rehabilitation and improvement in the quality of life to patients who may have exhausted personal or third party funding, b) treating so few patients that it makes the field unprofitable for manufacturers, and c) provides a dental solution to an essentially medical problem. Silicone rubber materials have been used for facial rehabilitation for more than 4 decades with few improvements. There is a clear need for new, alternative, and more economic materials for extraoral maxillofacial prostheses. Research at Gulf South Research Institute in New Orleans by the Principal Investigator and others in the 1970s and 1980s developed an alternative low-cost thermoplastic material (chlorinated polyethylene, CPE) that met all toxicological (safety) and physical (effectiveness) requirements. A limited clinical trial at the time yielded equivocal results when compared to conventional but costly silicone rubber products. This research will conduct a randomized, single-crossover, double-blinded Phase III clinical trial to evaluate a) experimental thermoplastic CPE, and b) control silicone (Silastic Adhesive A/MDX4-4210) materials for non-inferiority of CPE based on functional & subjective characteristics, and on the quality of life. Both prostheses will be attached with a skin adhesive. In the clinical trial, the patient's missing anatomy will be sculpted and a gypsum mold made. The silicone and the CPE prosthesis will be fabricated and delivered in random order to 50 patients at M.D. Anderson Cancer Center, University of Texas, Houston, 30 patients at Toronto Sunnybrook Regional Cancer Centre, and 20 patients at J.G, Brown Cancer Center, University of Louisville (100 total) to be worn for 4 months each. Detailed questionnaires will be filled out by the anaplastologist/laboratory technician, clinicians, before and after the prostheses are worn, and the patient. Quality-of-life before and after wearing each prosthesis will be tested with the Toronto Outcomes Measure for Craniofacial Prosthetics. These methods were designed to test future materials and techniques. The power analysis that determined that 100 patients would be needed used a non-inferiority approach from data in the previous study. The final analysis of the proposed clinical trial will also test for non-inferiority of CPE (experimental) compared to silicone rubber (control). The outcome will determine if the new material is at least equivalent to conventional silicone in important features. Longevity will be estimated by following patients. Material properties, their cost, and processing characteristics will affect use in underserved areas or developing countries.

44

Birth Defects

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

Project Title: NICOTINIC DEVELOPMENT

ACETYLCHOLINE RECEPTORS

&

NEURONAL

Principal Investigator & Institution: Pugh, Phyllis C.; Anatomy and Neurobiology; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Nicotine, as consumed through tobacco use, is a drug abused by nearly 47 million Americans. Understanding the consequences of nicotine exposure is therefore a major health issue in the United States and of interest at epidemiological, clinical and basic science levels. Of particular concern are the approximately 20% of women who smoke, two-thirds of whom continue to do so during pregnancy. Epidemiological studies link maternal smoking to low infant birthweight, reduced head size, congenital heart defects, isolated craniosynostosis, craniofacial anomalies, and limb malformations. As nicotine is a major toxic component of tobacco smoke and is present at equivalent levels in fetal and maternal tissues, it is strongly implicated as a causative agent of such defects. The physiological effects of nicotine are exerted by activation of nicotinic acetylcholine receptors (AChRs). AChRs are pentameric, ligand-gated ion channels, ubiquitously expressed in both the central and peripheral nervous systems, as well as in skeletal muscle. Thus, in addition to the established functions of AChRs in signaling, addiction, task attention, and neurological disease, AChRs are also likely to participate in smoking-related birth defects. The ability of nicotine to cause such defects is consistent with the appearance of AChRs in neuronal precursors and in the human CNS prior to cortical development. The early appearance of AChRs and their known ability to influence neuronal survival and process outgrowth directly implicate them in normal neuronal development in vivo. At present, however, developmental roles for AChRs are novel and remain poorly understood. This proposal will analyze the developmental significance of neuronal AChRs using the embryonic chick ciliary ganglion (CG) as a model system. CG neurons are ideally suited for such studies because they express well-defined AChR types having distinct properties and unique functions. Moreover, the CG is accessible to manipulation throughout development, both in vivo and in cell culture. A major AChR type is sensitive to blockade by (-bungarotoxin ((Bgt). The investigator has previously shown that these (Bgt-AChRs influence process outgrowth and promote neuronal survival in culture. Further, preliminary studies suggest that (Bgt-AChRs can influence synapse formation on CG neurons in culture. The experiments described here will extend these findings to the in vivo setting using retroviral delivery of mutated AChR genes into embryos during neuronal development. These alterations will be assessed for their impact on neuronal survival (Aim 1), synapse formation (Aim 2), and AChR distribution (Aim 3). The proposed studies are expected to provide new information concerning the developmental significance of AChRs in vivo. Fulfilling the goals of this project will aid in developing the investigator's scientific independence and is expected to reveal additional clues for understanding how nicotine abuse contributes to birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUTRIENT BIOMARKERS, GENES AND OROFACIAL CLEFTS Principal Investigator & Institution: Munger, Ronald G.; Associate Professor; Nutrition and Food Sciences; Utah State University Logan, Ut 84322 Timing: Fiscal Year 2001; Project Start 23-JUN-2000; Project End 31-MAY-2005

Studies

45

Summary: (Adapted from the Applicant's Description) Orofacial clefts are among the most common birth defects in the world yet little is known about their major causes and regional differences in occurrence. In our previous studies in the Philippines we recently found biochemical evidence that poor vitamin B-6 and folic acid levels of mothers are independently associated with increased risks of clefting and that the MTHFR C677T mutation is associated with a reduced risk of clefting. We propose to elaborate these methods for studying nutrient-gene interactions and apply them in a population-based case- control study of orofacial clefts in Utah with the following specific aims: (1) Children with orofacial clefts (n = 686) will be ascertained by the state- wide Utah birth defects registry and their mothers will be recruited as case participants; (2) Children without clefts (n= 686) will be randomly selected from Utah birth certificates and their mothers wIll be recruited as control participants; (3) Data will be collected on dietary patterns, smoking, alcohol use and other exposures using telephone-based interviews and mailed questionnaires; (4) Venous blood samples will be drawn from mothers, rapidly processed, and assayed for biochemical indicators of vitamin B-6 and folate status; (5) DNA from mothers, children, and fathers will be prepared and genotyped for polymorphic genetic markers related to vitamin B-6 and folate metabolism. The following hypotheses will be addressed: (1) Poor maternal vitamin B-6 status is independently associated with increased risk of orofacial clefts; (2) Poor maternal folate status is independently associated with increased risk of orofacial clefts; (3) The MTHFR C677T allele is associated with a reduced risk of clefting. In addition the association between allelic variants of other folate- and vitamin B-6-related genetic markers and the risk of orofacial clefts will be examined; (4) The nutrients and candidate genes mentioned above interact, additively or multiplicatively, to increase the risk of orofacial clefting. Our multidisciplinary study of maternal nutrition and risk of clefting in the context of genes related to metabolic pathways may lead to a better understanding of the causes and prevention of orofacial clefts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVINE MODEL SYSTEM FOR ALCOHOL RELATED BIRTH DEFECTS Principal Investigator & Institution: Cudd, Timothy A.; Veterinary Physiology & Pharmacology; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAR-2007 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PATTERNING OF THE OPTIC VESICLE BY EXTRINSIC FACTORS Principal Investigator & Institution: Fuhrmann, Sabine; Ophthalmology and Visual Scis; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term goal of this project is to understand how cellular and tissue-tissue interactions regulate development of the central nervous system. Disruption of tissue-tissue interactions can lead to a wide range of serious birth defects affecting the brain and eye, such as holoprosencephaly, congenital anophthalmia, microphthalmia, and anencephaly. Understanding the normal process of development will allow for better prevention and treatment of such defects. It is proposed to study the role of signaling molecules involved in these interactions using the embryonic eye as a model system for forebrain development, where the same

46

Birth Defects

mechanisms most likely regulate regional specification. Classical embryological studies have shown that the extraocular tissues are required for normal eye growth and differentiation. At present there is little information about the signals involved in these interactions. In explant cultures of optic vesicles from chick embryos, removal of the extraocular mesenchyme severely interferes with the formation of the retinal pigmented epithelium (RPE). The TGFbeta family member activin has been shown to be a candidate signal that exactly mimics the effects of the extraocular mesenchyme on RPE development in vitro. It is proposed to test the hypothesis whether the activin signaling pathway is required for RPE formation in the chick embryonic eye (Aim 1). To interfere with the activin signaling pathway in the developing RPE, soluble activin type II receptors will be applied as well as ectopic expression of antagonistic Smads (Smad6, 7) and truncated activin type II receptors using electroporation. It will be determined whether activin or a related signal is produced by the extraocular mesenchyme (Aim 2). Since cranial mesenchyme contains the inducer of RPE development, sufficient amounts of this tissue can be isolated for a degenerate PCR strategy. Subsequently, the identified molecule will be cloned and tested for the RPE-promoting activity in explant cultures and by transfection of chick embryos. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOGENETIC DETERMINANTS OF HUMAN BIRTH DEFECTS Principal Investigator & Institution: Mitchell, Allen A.; Professor/Director; Slone Epidemiology Unit; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the Applicant's description) The investigators propose to apply state-of-the-art pharmacogenetic and pharmacoepidemiologic research methods and two large pharmacoepidemiologic databases to assess the genetically-mediated role of prescription and OTC medications in the etiology of human birth defects. A particular focus relates to the increased risk of a common birth defect, persistent pulmonary hypertension (PPHN) of the newborn, following exposure late in pregnancy to nonsteroidal anti-inflammatory drugs (NSAIDs), and particularly ibuprofen, a drug that is among the most commonly used agents in pregnancy. In aim 1, the investigators will apply data from an ongoing epidemiologic study of PPHN to test the hypothesis that this increased risk is related to genetically mediated factors involved in the metabolism of NSATDs. In aim 2, they propose to use sophisticated technologic approaches to identify mutations in the CYP2D6, CYP3A4, and CYP3A7 and other gene promoters that modify developmental and tissue-specific expression of those genes in the fetus and newborn. Once polymorphisms are identified, the investigators will systematically evaluate their possible etiologic roles in humans by applying these new tools to current and future data collected by the SEU-BDS and the CDC-NBDPS, two large and unique epidemiologic birth defect studies that collect both genetic material and detailed information on antenatal drug exposures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PREVENTION OF NEURAL TUBE DEFECTS BY IMMUNE STIMULATION Principal Investigator & Institution: Hrubec, Theresa C.; Biomedical Scis/Pathobiology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060

Studies

47

Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Dr. Terry Hrubec received the D.V.M. and Ph.D. degrees and is embarking on a research career. She is a highly motivated scientist who wishes to make a career shift from clinical pathology and immunology of aquatic species to research in mammalian cellular and molecular immunology. This award would offer Dr. Hrubec an opportunity to strengthen and expand research skills by affording training in molecular mechanisms of developmental abnormalities and using animal models of human disease. The proposed research investigates the mechanism by which maternal immune stimulation prevents valproic acid (VA) induced birth defects. VA, a drug commonly used to treat epilepsy, is teratogenic and induces neural tube defects (NTDs) in one to two percent of exposed fetuses at a rate 20 times higher than in the general population. In what the investigators feel is paradigm-changing work, data from the investigators' laboratory have conclusively demonstrated that non-specific activation of the maternal immune system in rodents can dramatically reduce a variety of chemical-induced birth defects, including VA induced NTDs. Additionally, the investigators have shown that such maternal immune stimulation normalizes teratogenaltered expression of a few selected fetal cell-cycle/apoptotic regulatory genes in urethane-induced cleft palate. A more focused examination of altered gene expression in VA induced NTDs is now logical. Specifically, the investigators will test the hypotheses that: 1) VA affects the expression of genes regulating neural tube development, and that maternal immune stimulation normalizes gene expression through regulatory proteins (cytokines) secreted by activated immune cells; and 2) folic acid supplementation protects against NTDs by cytokine-related mechanisms which may in part be similar to that resulting after maternal immune stimulation. These studies are expected to significantly increase the investigators' understanding of genetic mechanisms by which maternal immune modulation reduces this specific birth defect. Clearly, this research is of importance to human health, as determining the mechanisms involved will improve the understanding of this disorder leading to a prevention or cure. This research will be conducted under the guidance of Drs. Steven Holladay and Ansar Ahmed of the Virginia-Maryland Regional College of Veterinary Medicine at the VPISU, and will offer excellent training and career development for Dr. Hrubec. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CHROMOSOME SEGREGATION Principal Investigator & Institution: Biggins, Susan; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: Accurate cell division depends upon proper chromosome segregation into daughter cells. Defects in chromosome segregation lead to genetic instability and aneuploidy, hallmarkers of cancer and birth defects. Chromosomes segregate using their kinetochores, the specialized protein structures that are assembled on centromeric DNA sequences and mediate attachment to the mitotic spindle. Although many kinetochore components have been identified, it is unknown how kinetochores are regulated to mediate chromosome segregation. The long-term goal of this project is to elucidate the regulation and mechanisms of kinetochore function and chromosome segregation using the budding yeast Saccharomyces cerevisiae is a model system. A key regulator of kinetochore function is the conserved Ip11/aurora2 protein kinase. Since defects on the yeast Ip11p kinase lead to aneuploidy and the human aurora2 kinase is an oncogene, studies on the kinase are important to understanding both chromosome segregation and cellular transformation. This proposal This proposal focuses on the

48

Birth Defects

Ip11/aurora2 kinase and another conserved kinetochore component, the histone H3 variant Cse4p, as a means toward elucidating the mechanisms of chromosome segregation. The specific aims include: 1) analyzing Ip11p and Cse4p assembly into kinetochores to gain insight into mechanisms of kinetochore assembly, 2) investigating the regulation and substrates of the Ip11p kinase to understand how it regulates chromosome segregation, 3) examining the role of Ip11p in the spindle checkpoint, and 4) investigating the kinetochore functions of the Ip11p and Cse4p proteins to understand how kinetochores are regulated. These studies will lead to a better understanding of the mechanisms of chromosome segregation and the role of the Ip11/aurora2 kinase in genomic stability, studies may elucidate details about the generation of cancer and provide new avenues for therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GEMININ EXPRESSION IN EMBRYONIC ECTODERM Principal Investigator & Institution: Kroll, Kristen L.; Molecular Biol & Pharmacology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Our long-term objective is to dissect the molecular circuitry that underlies cell fate determination in the neurectoderm during early vertebrate embryogenesis. Information obtained in these studies may ultimately impact multiple human health issues, including our ability to manipulate embryonic stem cells for human therapies in the nervous system, and our understanding of the molecular basis of birth defects, including holoprosencephaly and spina bifida. These birth defects are among the most common congenital malformations in humans. Our general strategy is to focus upon a group of genes that act as primary effectors of neural fate during early embryogenesis. Expression of these genes in the future neural plate represents the earliest transcriptional response of ectoderm to neural-inducing signals from adjacent cells. This expression demarcates the embryonic ectoderm into neural versus non-neural territories. It is not known how this transcription arises or which molecular determinants and signaling pathways are direct regulators. Here, we have used a manipulatable transgenic Xenopus embryo system to reconstitute cis-regulatory controls underlying the early neural expression of one such gene, geminin. We show that 5' regulatory sequences from geminin recapitulate its expression and respond to inductive signals in the same manner as the endogenous gene. We propose use of several approaches to identify discrete cis-elements and protein complexes that directly control the onset of geminin's initial neural-specific transcriptional program, including injection and transgenic methodologies in vivo and various molecular methodologies in vitro. These studies should fill a critical gap in our understanding of the molecular basis of neural cell fate determination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REGULATION FRAMESHIFTING

OF

GENE

EXPRESSION

BY

RIBOSOMAL

Principal Investigator & Institution: Dinman, Jonathan D.; Associate Professor; Cell Biology & Molecular Gen; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005

Studies

49

Summary: (provided by applicant): Faithful maintenance of translational reading frame is a basic requirement for translation of genetic information from genes into proteins. Exceptions to this rule have been characterized mostly in RNA viruses, where specific cis-acting mRNA signals induce elongating ribosomes to shift reading frame. Given that many basic biological regulatory mechanisms have been first in viral systems, we hypothesize that programmed ribosomal frameshifting is utilized to regulate the expression of a significant subset of cellular genes as well. If so, this would represent a significant shift in our view of protein translation, and may have significant impact on our understanding of many of the underlying causes of birth defects, cancer and aging. Preliminary studies are presented supporting this hypothesis. These include bioinformatic, RNA-blot, and a preliminary set of DNA microarray analyses. The proposed studies will expand upon a DNA microarray approach to identify cellular mRNAs that are regulated by programmed -1 ribosomal frameshifting (-1 PRF). The overall strategy will be to identify cellular mRNAs that are specifically stabilized under conditions where -1 PRF is inhibited, and conversely, those that are destabilized when -1 PRF is stimulated. The data generated from these experiments will be compared with one another and with our database of consensus -1 PRF signal containing genes in order to identify the best candidates for further characterization with regard to the role that -1 PRF may play in theregulation of their expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF UTERINE SMOOTH MUSCLE EXCITABILITY Principal Investigator & Institution: Davy, Kevin P.; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: Preterm births account for only 10 percent of all deliveries, but are associated with over 80 percent of newborn deaths and more than 95 percent of major newborn morbidity. The lack of understanding of the mechansims regulating uterine contraction has hampered progress towards an effective treatment for this reproductive health problem. Currently used tocolytics have little effect in prolonging gestation, necessitating the investigation of other mechansims of prevention. One potential class of therapeutic targets is potassium channels, due to their ability to potently buffer cell excitation. Electrophysiological reports have shown that myometrial cells contain a variety of K+ channel types that may be potential therapeuric targets, including the large-conductance calcium-activated K+ channel (BKCa channel). Blockage of BKCa channels depolarizes myometrial cells and increases contractile activity while activation of these channels by agonists and beta-adrenergic agents induces potent uterine relaxation. Interestingly, the activation of the BKCa channel by phosphorylating agents, Ca2+, or voltage is dependent on whether it is isolated from non-pregnant or pregnant tissue. Recent evidence illustrates the ability of this channel to undergo alternative splicing in the presence of stress hormones, yielding variants that differ in their sensitivity to intracellular Ca2+ and voltage. Sensitivity to these agents is also dependent on the association of the BKCa channel with its ancillary beta subunit. This suggests that alternative splicing or modulation of beta subunit association may be mechanisms regulating BKCa channel diversity in uterine smooth muscle during gestation. While this channel appears to be an important regulatory component of uterine excitability, its role in modulating myometrial contraction during gestation remains unknown. The specific objective of this proposal is to detemine whether modulation of BKCa channel splice variant expression or beta subunit association correlates to a functional difference in uterine excitability during gestation. Alterations

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Birth Defects

in BKCa channel splice variant expression and function during gestation will be investigated by molecular charactization in combination with electrophysiological and contraction measurements in mice. The specific aims of this proposal are to: 1) compare transcript and protein expression patterns of BKCa channel isoforms in mouse uterine smooth muscle during gestaiton, 2) elucidate BKCa channel beta subunit transcript and protein expression during gestation and detemine whether its assembly with the alpha subunit is modulated during pregnancy, 3) determine the contribution of BKCa channel splice variants to the regulation of uterine smooth muscle contraction during gestation, and 4) characterize the expression of the splice variants of the BKCa channel alpha subunit following stimulation with estrogen and progesterone. Preterm labor is a major health problem, especially given the risks it carries with respect to birth defects and the costs associated with premature delivery. Whether the BKCa channel could be a future target for tocolytic drug therapy is thus a significant question to examine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH ON THE SCOPE AND CAUSES OF STILLBIRTH IN THE US Principal Investigator & Institution: Stoll, Barbara J.; Pediatrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This proposal demonstrates the ability and commitment of the Emory University Schools of Medicine and Public Health and The Metropolitan Atlanta Stillbirth Study Coalition (MASSC), a consortium of 6 hospitals, to participate in the NICHD initiative to study the scope and causes of stillbirth in the United States. The MASSC represents the academic, private and public sectors, with almost 40,000 deliveries/year at these hospitals. Over 90% of women who live in a Catchment Area of 100 Census Tracts in DeKalb, Fulton and Gwinnett Counties deliver in one of these hospitals (over 9000 deliveries/year). Population in the Catchment Area is racially, ethnically, and economically diverse. From 1995-99, 280 women in the Catchment Area delivered a stillbirth of > 20 weeks' gestation in MASSC hospitals (7.7 stillbirths per 1,000 deliveries > 20 wks). Data on prenatal care, maternal race, gestational age, cause of death are presented and compared to the entire 3-County area, the 5-County area of the Metropolitan Atlanta Birth Defects Monitoring Program, and the State of Georgia. A plan to enhance the existing perinatal data system is presented. The multidisciplinary team of investigators includes scientists from the Emory Schools of Medicine and Public Health, U.S. Centers for Disease Control and Prevention, and Georgia Department of Human Resources. They bring a breadth of expertise to this study that includes pediatrics/neonatology, obstetrics/perinatology, epidemiology/public health, pediatric/perinatal pathology, placental function, infectious diseases, hematology, genetics, birth defects, and neurology/neuropathology. The group has a long history of successful funded research, publications in relevant areas, and active involvement with other multicenter studies and multicenter Networks. Dr. B. Stoll (PI) is an internationally recognized clinical and epidemiologic investigator. She is the PI at Emory for the NICHD Neonatal Research Network and co-chair of an Institute of Medicine committee, "Improving Birth Outcomes in Developing Countries." Dr Carol Hogue (co-PI) is an internationally recognized reproductive health epidemiologist and PI of multicenter collaborative studies. A concept proposal, "The association of stillbirths with maternal and fetal thrombophilia genotypes," is presented. The investigators are committed to working

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collaboratively with other clinical centers and scientific groups to achieve the goals of the NICHD Stillbirth Network. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF HEPARAN SULFATE IN FGF ACTION Principal Investigator & Institution: Rapraeger, Alan C.; Professor; Pathology and Lab Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-MAR-2006 Summary: The fibroblast growth factors (FGFs) are a family of 22 related polypeptides that regulate the proliferation, differentiation and migration of a wide variety of cell types. FGF1 and FGF2 are the prototypes of the family initially described as promoting neuronal proliferation, neurite extension and survival, and fibroblast growth, respectively. Many of their native roles are in early development, where they control early aspects of embryonic differentiation. Thus, an understanding of how these growth factors signal, and how this signaling may be regulated or controlled, will have direct applicability to the treatment of cancer and birth defects. One of the intricacies of FGF signaling is that two types of receptors collaborate at the cell surface to generate the signal. One of these types is a family of receptor tyrosine kinases The other type if heparan sulfate proteoglycans. The FGFs are united by a common affinity for haparan sulfate, the highly sulfated glycosaminoglycan chain found on heparan sulfate proteogycans of the cell surface and the extracellular matrix. In addition, the receptors have a heparan sulfate- binding domain, and successful docking of the FGF with the receptor relies on both proteins recognizing a common domain in the heparan sulfate chain. An important feature of heparan sulfate is its variable sulfation patterns. Our hypothesis, for which we now have evidence, is that this sulfation pattern may be cellor tissue-type specific. Thus, although it is variable, it is not random. This proposal will use FGF and FGF receptor probes to detect structural differences in heparan sulfate during early mouse development. The probes will be used to isolate the specific heparan sulfate sequences to which they bind, and these sequences will then be identified chemically. The long term outcome of this work will be left the derivation of chemical mimetics that can be used as therapeutics in the treatment of cancer and the prevention of birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEARCHING FOR SUSCEPTIBILITY GENES FOR ORAL CLEFTS Principal Investigator & Institution: Beaty, Terri H.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Oral clefts are complex and heterogenous birth defects, and genetic factors are clearly important in their etiology. It has proven difficult, however, to map susceptibility genes through linkage studies. We have been involved in family studies of oral clefts for some time, and have accumulated a number of multiplex families (i.e., those ascertained through two or more probands with an oral cleft) suitable for linkage analysis. As part of the Comprehensive Center for Oral Health Research, we propose to use multiplex families ascertained from four collaborating centers (Mid-Atlantic region of the U.S., Mexico City, Buenos Aries and Prague) to conduct a genome wide search for susceptibility genes. Recent advances in technical methods now make it possible to genotype large numbers of markers on individuals in multiplex families and recent statistical advances make it easier to test for linkage heterogeneity when mapping a

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complex disorder such as oral clefts. The specific aims of this study are: 1) To conduct a genome wide search for susceptibility loci using multiplex families ascertained from our collaborating centers: Mid-Atlantic, Mexico City, Buenos Aires, and Prague. This mapping effort will focus on efforts to detect linkage and test for linkage heterogeneity, both among families drawn from different populations and within samples of families from a single population. Admixture tests for linkage heterogeneity and conditional approaches for identifying linkage from multiple markers will be employed. 2) To fine map chromosomal region suggesting linkage using these same individuals to identify variant alleles that could be responsible for oral clefting. Results of this study should yield a better understanding of the gene or genes contributing to risk of oral clefts and may suggest strategies for either preventing these birth defects or for identifying individuals at highest risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEGMENTAL ANEUSOMY BETWEEN BLOCKS OF DUPLICATED DNA Principal Investigator & Institution: Eichler, Evan E.; Assistant Professor; Genetics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 03-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): One of the major goals of the field of human genetics is to define the relationship between human genotype and phenotype. Much of our assessment of genotypic variation has been focused on small scale, single nucleotide events. Our understanding of the molecular basis of disease, however, has begun to reveal that large-scale differences including micro duplications and micro deletions contribute significantly to childhood disease, disease susceptibility and normal variation in the population. Despite its importance, there has been no systematic study of this form of genotypic variation. The long-term objective of this proposal is to investigate the pattern and nature of this large-scale variation. Our approach will be directed to regions of the genome that contain highly homologous duplicated sequence and therefore have an increased probability of genomic gain and loss. This proposal is a collaborative effort that brings together expertise in genome structure, array comparative genomic hybridization technology and mental retardation. The specific aims of this proposal are (1) to identify and validate all intrachromosomally duplicated regions within the human genome, (2) to develop a set of large-insert clones bracketed by duplicated sequence to be placed on a CGH microarray platform for genome-wide screening, (3) to assess copy number variation within both normal individuals and children with idiopathic mental retardation and (4) to validate the extent, frequency and inheritance pattern of these large structural "polymorphisms". This project aims to address two fundamental questions; what is the nature and frequency of duplication-mediated structural polymorphisms within the human genome? Are there an excess of de novo events among children with mental retardation and congenital birth defects? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SEMA3D ROLE IN RETINAL AXON GUIDANCE AND CELL MIGRATION Principal Investigator & Institution: Halloran, Mary C.; Zoology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007

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Summary: (provided by applicant): Semaphorins have been implicated in the regulation of axon pathfinding, sometimes acting as inhibitory guidance molecules, and other times attractive. An understanding of the complex processes involved in promoting and inhibiting axon growth will be crucial for understanding both diseases of neural development, and the conditions under which axon regeneration after injury can occur. Semaphorins also are thought to play a role in controlling the related processes of cell migration during development, metastasis and invasive growth. Cranial neural crest cells migrate from the neural tube to form craniofacial structures and peripheral nervous system. Errors in migration of cranial neural crest during development underlies many birth defects in craniofacial structure. An investigation of the mechanisms by which semaphorins control neural crest migration will provide insight into craniofacial development, and perhaps also general mechanisms of invasive growth involved in cancer progression.The aim of this application is to understand the in vivo function of one semaphorin, Sema3D, in guiding retinotectal axon pathfinding and neural crest cell migration in the developing zebrafish. Sema3D's role in guiding retinal axons across the midline and in topographic mapping onto the tectum will be investigated. In addition, Sema3D's role in controlling cell motility will be investigated to test the hypotheses that Sema3D induces the onset of neural crest migration, and/or maintains separation of migrating neural crest streams. Our strategy is to examine effects of both Sema3D ectopic expression and Sema3D loss-of-function on the development of these systems, and on dynamic behaviors of living growth cones and migrating neural crest cells in vivo. The zebrafish embryo is ideally suited to the combination of approaches we have developed. With transgenic zebrafish, Sema3D can be misexpressed in select cells at any desired developmental stage. In addition, Sema3D function can be disrupted with antisense or dominant negative methods. Time-lapse microscopy allows direct visualization of the responses of living growth cones or migrating cells in the embryo. Thus the proposed experiments will likely provide novel insights into how semaphorins regulate retinal axon development and neural crest cell migration within the complex in vivo environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNAL TRANSDUCTION IN VERTEBRATE EMBRYOGENESIS Principal Investigator & Institution: Costantini, Franklin D.; Professor; Genetics and Development; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2007 Summary: (provided by applicant): This proposal concerns the roles of Axin and the related gene Axin2 in regulating the canonical Wnt signal transduction pathway during mammalian embryogenesis. The Wnts are a family of secreted factors that play important roles in cell proliferation, patterning and differentiation during development. Axin is a critical component of a protein complex that controls intracellular signaling downstream of Wnts, by regulating the levels of ?-catenin, a transcriptional co-activator and a key effector in the pathway. Axin2 is believed to have a similar function, although it is not as well characterized. Mutations in both genes in humans have shown that they are tumor suppressors, consistent with their roles in negatively regulating the Wnt pathway. The analysis of mice with mutations in Axin and Axin2 have revealed that these genes are important for early axial patterning, as well as for craniofacial and brain development. Craniofacial development is a complex process that involves interactions between the surface ectoderm, endoderm, mesoderm and the neural crest, and it is highly susceptible to genetic and environmental perturbations, as craniofacial abnormalities are among the most common birth defects in humans. The Wnt signaling

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pathway has been implicated in craniofacial development through several mouse mutations. In this proposal, the hypothesis will be tested that Axin and Axin2 are required to negatively regulate the response to certain Wnts by the cranial neural crest cells that form much of the face, and that mutations in Axin and Axin2 lead to inappropriate activation of the Wnt pathway. This will be addressed by analysis of mutant mice, as well as through the conditional manipulation of the Wnt pathway in the cranial neural crest, using transgenic approaches. To understand how Axin and Axin 2 cooperate during development, it is important to define the extent to which they are functionally redundant, and this issue will be investigated through a gene replacement strategy in mice. Finally, to test in vivo the importance of specific domains of Axin that are believed to mediate its functional interactions with other components of the pathway, several novel mutant alleles of Axin will be generated, and examined for their effects on mouse embryogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF MEGALIN IN CRANIOFACIAL DEVELOPMENT Principal Investigator & Institution: Argraves, W Scott.; Associate Professor; Cell Biology and Anatomy; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Craniofacial malformations, including a range of forebrain defects collectively known as holoprosencephaly (HPE), are the most common birth defects that occur in humans. The variation in the characteristics defining HPE suggests that multiple genes contribute to the syndrome. Mutation of the gene for sonic hedgehog (Shh), a signaling protein known for its crucial role in patterning tissues, including structures of the face, brain, spinal cord and eye has been shown to cause HPE. A HPE phenotype has also been described in mice that are deficient in the expression of megalin, an endocytic receptor related to the LDL receptor. Our studies have revealed previously unknown relationships between megalin, Shh and the Shh receptor, patched-1 (Ptc-1). These include the findings that megalin binds Shh and mediates its endocytosis and that megalin also influences subcellular trafficking and proteolytic processing of Ptc-l. W8 therefore hypothesize that megalin activity is an integral part of the mechanism by which Shh acts to control craniofacial morphogenesis. To test this hypothesis, experimentation is proposed to investigate megalin-mediated intracellular trafficking of Shh. Our results indicate that megalin-internalized Shh bypasses lysosomes. Given the fact that megalin is known to mediate transcytosis of several ligands; a major emphasis is to determine if megalin mediates transepithelial transport (transcytosis) of Shh. Such transcytosis would represent a novel mechanism to explain long range Shh signaling during development. Experimentation will also focus on establishing the relationship between megalin and Ptc-1, including characterization of the role of megalin in regulating targeting of Ptc-1 to lysosomes and proteolytic processing of Ptc-l. Proteolytic processing of Ptc-1 is a new observation that is made more interesting by our finding that a carboxy-terminal fragment of Ptc-1 is translocated to the nucleolus, suggestive of a role in regulation of gene expression. Additional experimentation is directed towards establishing the role of megalin in regulating Shhdependent gene expression important for eye development and neuron specification. The proposed experimentation is expected to lead to new insights into the mechanism by which Shh signaling controls craniofacial development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF NEURAL CREST IN FACIAL PATTERNING Principal Investigator & Institution: Schneider, Richard A.; Assistant Professor; Orthopaedic Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): My long-term career objective is to investigate the cellular and molecular bases for normal and abnormal facial development. My research will provide a foundation for generating biologically based therapies to treat facial malformations in humans. To prepare for my career, I have received multidisciplinary training in embryology, anatomy, developmental molecular biology, and craniofacial anomalies. Through this diverse background I have acquired skills for studying complex cellular and molecular mechanisms that pattern the developing face. Future progress in understanding normal and abnormal facial morphogenesis will come from discovering and experimentally manipulating molecular and cellular signals that pattern the skeletal, muscular, nervous, and vascular systems of the head. Therefore, in order to provide a substantial contribution to this area of research, I am focusing my work on the regulation of cell differentiation, which is an essential component of craniofacial development. Disruptions to this process result in a range of human birth defects. For example, premature cell differentiation within the osteogenic front of cranial sutures causes craniosynostoses. Conversely, a delay in differentiation of median edge epithelium leads to clefting of the secondary palate. Thus, the timing of differentiation among multiple populations of embryonic cells is a prerequisite for normal facial patterning. Cellular and molecular mechanisms through which cranial populations of neural crest, ectoderm, and mesoderm learn when to differentiate into discrete facial structures such as bone, epidermis, and muscle are unknown. I hypothesize that in the developing face, neural crest cells regulate their own temporal differentiation as well as that of ectoderm and mesoderm. To test this hypothesis, I will perform a series of neural crest transplants between two avian species that have significantly different maturation rates, which will alter temporal information being conveyed among populations of donor and host cells. Using a variety of morphological, cellular, and molecular approaches, my analyses will determine whether donor neural crest-derived cartilages and bones, as well as host-derived epidermal and muscular structures develop on a timetable of the donor, host, or a combination of both species. This project is significant in using a novel approach to investigate regulation of facial growth and will provide valuable insights on birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF TGF-BETA3 IN PALATOGENESIS Principal Investigator & Institution: Kaartinen, Vesa M.; Assistant Professor; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-DEC-2004 Summary: The long-term goal of this proposal is to define specific molecular mechanisms of TGF-beta3-induced palatal fusion. During development TGF-beta3 expression is both spatially and temporally restricted. Exceptionally high expression levels have been found specifically in prefusion palatal epithelium. Concordant with this surge of TGF-beta3 expression, homozygous TGF-beta3-deficient mice suffer from bilateral clefting of the secondary palate. It has been suggested that during epithelial fusion, TGF-beta3 triggers epithelio-mesenchymal transdifferentiation and associated degradation of the basement membrane, processes necessary for successful palatal

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fusion. The combined data, including expression pattern and level of TGF-beta3 in prefusion palatal shelves, complete penetrance of cleft palate in TGF- beta3 null mutant mice and failure of TGF-beta3-deficient medial edge epithelial cells to transdifferentiate from epithelial cells to mesenchymal cells lead to the formulation or the following hypotheses: TGF beta3 is a master switch, capable of initiating a cascade of molecular events leading to successful midline epithelial fusion during palatogenesis. To test this hypothesis we will utilize TGF-beta3 null mutant mice to investigate TGF-beta3 signaling and downstream biological responses. The proposed studies have been organized to three different Aims: expression and function of TGF-beta type I receptors and their down- stream signaling molecules, Smads in Aim 1, role of epithelial mastergenes and key molecular switches in epithelio-mesenchymal transdifferentiation during epithelial fusion in Aim2, and function of metalloprotemases and their inhibitors during associated degradation of the basement membrane in Aim 3. These studies will eventually improve our understanding of the pathogenetic mechanisms that lead to formation of cleft palate, one of the most common congenital birth defects in human. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOXOPLASMA DEVELOPMENT AND CELL CYCLE Principal Investigator & Institution: Kim, Kami; Associate Professor; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract): The obligate intracellular parasite Toxoplasma gondii is an important opportunistic pathogen in immunocompromised individuals such as AIDS patients. T. gondii also causes devastating birth defects in neonates. These studies are designed to provide further understanding of the mechanisms by which T. gondii is able to persist and cause disease within its human host. The salary support provided by the K02 award will enable Dr. Kim to have "protected time" to concentrate upon her efforts to adapt technology and expertise from other areas of biological investigation, specifically eukaryotic cell cycle regulation and signal transduction, to the study of cell cycle and Toxoplasma development. Within human hosts, T. gondii exists as tachyzoites, which are responsible for clinically apparent disease, and as bradyzoites, which are latent encysted forms. With waning immune function, slow-growing bradyzoites can reactivate to the rapidly proliferating tachyzoite forms, leading to Toxoplasma encephalitis. Given the marked difference in proliferation of the tachyzoite compared to the bradyzoite and Toxoplasma's inability to replicate outside host cells, cell cycle regulation is undoubtedly critical in Toxoplasma development and pathogenesis of disease. It is clear from studies of other eukaryotes that responses to signals for development or differentiation occur at specific points within the cell cycle and result in a coordinate modulation of stage-specific gene expression and cell cycle progression. The candidate hypothesizes that unique aspects of T. gondii cell cycle regulation coordinate the processes leading to disease pathogenesis and intracellular survival. In Aim 1, regulation of cell cycle gene expression in T. gondii will be analyzed focusing on ribonucleotide reductase (RNR) gene expression. In Aim 2, expression and function of T. gondii cyclin dependent kinases (cdk) will be examined using immunofluorescence, flow cytometry, Northern and Western blotting. Constructs with mutant cdks will be transfected into tachyzoites to determine the role of cdks in cell cycle progression. Finally, in Aim 3, the relationship of cell cycle regulation and T. gondii bradyzoite development will be studied. Cell cycle markers will be used to examine the cell cycle dependence of bradyzoite development. Cell cycle and bradyzoite reporter constructs will be used to test the effects of cell cycle inhibitors and potential

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inducers or inhibitors of differentiation on gene expression. These will be the initial experiments in a long-term effort to define the role of cell cycle regulation in Toxoplasma tachyzoite-bradyzoite differentiation and virulence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSCRIPTIONAL DEVELOPMENT

REGULATION

IN

EARLY

FLOWER

Principal Investigator & Institution: Chory, Joanne; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd San Diego, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's Description): The long-term objective of this proposal is to understand how transcriptional programs underlying organ-specific patterns of development are initiated. The experimental system is floral patterning in the model plant Arabidopsis, which is particularly suited for genetic and molecular studies because of its short generation time, small genome, and facile DNA-mediated transformation. The specific problem to be investigated is how the LEAFY transcription factor interacts with other factors to regulate flower-specific gene expression. By comparing the processes of pattern formation in animals and plants -- which evolved multicellularity independently -- universal principles underlying these processes can be uncovered. The health relevance of such knowledge relates to birth defects resulting from aberrant pattern formation caused by environmental effects, and to genetic disorders disrupting genes encoding developmental regulators. LEAFY, which is the earliest known transcription factor to be specifically activated in floral primordia, is both necessary and sufficient for converting vegetative shoots into flowers. A unique feature of LEAFY compared to animal transcription factors is that it can be exported to adjacent cells, where it can activate direct target genes. One class of direct target s, homeotic genes that control floral organ fate, has been previously identified, and includes the AGAMOUS gene. However, other targets besides homeotic genes must be required for flower formation, since flowers are distinguished from shoots not only by differences in organ identity but also in organ arrangement. Experiments are proposed (1) to study AGAMOUS regulation as a proxy for transcriptional control during plant development; (2) to reveal the global expression program induced by LEAFY with the goal of uncovering new classes of target genes; and (3) to identify the cis- and transrequirements for LEAFY movement with the goal of elucidating this unique mode of cell-cell communication. The proposed experiments will advance our understanding of how widely expressed, early acting genes participate in the regulation of later-acting genes that are expressed only in restricted regions of an emerging organ primordium. The experiments will also reveal how different stem cells communicate to effect coordinated development of the flower. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRISOMY NONDISJUNCTION

21:

RISK

FACTORS

FOR

CHROMOSOME

Principal Investigator & Institution: Sherman, Stephanie L.; Professor of Human Genetics; Genetics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 22-JUN-2000; Project End 31-MAY-2005 Summary: Although the chromosomal basis of Down syndrome (DS) has been known for over 30 years, there is still a surprising lack of knowledge about causes of nondisjunction leading to trisomy 21, or to any other human trisomy. Also, little is

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known about risk factors that predispose DS individuals to specific birth defects. Based on our ongoing studies, we have identified important correlates to nondisjunction. We have found strong evidence that altered recombination along the nondisjoined chromosome 21 is associated with increased risk for all types of meiotic errors. New data suggest that this altered recombination may be a cell- wide phenomenon. Our preliminary analyses of environmental factors suggest that smoking and oral contraceptive use around the time of conception may predispose to one specific type of nondisjunction error, implying that risk factors affect different stages of meiosis. The success of our current studies has resulted from the combined use of cytogenetic, molecular, and epidemiological methods to study DS not as a single entity, but as subgroups defined by the type of error. We propose to extend these studies to investigate: 1) the relationship of altered recombination and maternal age; 2) individual variation in cell- wide recombination as a risk factor for nondisjunction; 3) the role of recombination in paternal nondisjunction; and 4) environmental and maternal risk factors for nondisjunction and for DS-associated birth defects. These specific aims require a substantial increase in the study population. We have a unique opportunity to ascertain over 1350 cases of trisomy 21 from well- established birth defect surveillance systems using the infrastructure established by the National Birth Defects Prevention Study. Six of the study sites (AR, CA, GA, IA, NJ, NY) will contribute a populationbased sample of cases and controls. All sites are experienced in identifying, tracking, interviewing, and collecting biological samples from families with birth defects. The data resulting from this proposal will provide a valuable resource to uncover the etiology and consequences of nondisjunction of chromosome 21. These studies parallel those on other significant trisomies proposed by Dr. Terry Hassold in the companion IRPG application. Indeed, the questions and methodological approaches are nearly identical. By combining a large, population-based analysis of trisomy 21 with analyses of other autosomal and sex chromosome trisomies, we intend to characterize the genesis of the most common and clinically important human chromosome abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TROPHOBLAST MDR EFFLUX SYSTEM AND FETAL PROTECTION Principal Investigator & Institution: Audus, Kenneth L.; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 02-MAY-2002; Project End 31-MAR-2007 Summary: Recent studies in animal models have indicated that the multi-drug resistant (MDR) gene product, P-glycoprotein (Pgp), of the placenta has a significant role in reducing chemical exposure to the fetus and the incidence of birth defects. Pgp is an active, polyspecific membrane- bound transporter expressed in tumor and normal tissues, including the placenta. In humans, Pgp is localized to the syncytio- and cytotrophoblasts and is expressed throughout pregnancy. However, Pgp's role in controlling the disposition of drugs and steroids between the fetal and maternal compartments is unknown. The objective of this proposal is to characterize the Pgp efflux mechanism of the trophoblast with respect to expression and transporting xenobiotics (e.g., anti-cancer agents, phenobarbital, rifampicin) and steroids of pregnancy (e.g., progesterone) and its regulation by these substances. Under Aim 1o of this proposal we will elucidate (a) the mRNA and protein expression, and (b) the localization of MDR1 in the human trophoblast. In Aim 2 we will determine (a) the functional significance and (b) the asymmetry of human trophoblast transport of selected xenobiotics and steroid hormones. Aim 3 studies are directed at characterization of the regulatory mechanism(s) by which certain xenobiotics and steroid hormones control (a) the expression and (b) the

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function of MDR1 of the human trophoblast. We expect that at the conclusion of this proposal we will have established the role of Pgp and related mechanisms (e.g. breast cancer resistance protein) of the trophoblast in transporting substrates that include xenobiotics and the steroid hormones. We also expect to establish a putative role and the biochemical mechanisms by which certain xenobiotics and steroid hormones modulate Pgp expression and/or function. Our long term goal is to develop a detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human detailed understanding of the mechanisms controlling drugs and drugs of abuse distribution across the human trophoblast and to identify appropriate in vitro techniques that can lead the way to the future design and development of drugs for pregnancy that reduce risk to the health of the fetus and the mother. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN A SIGNALING AND CARDIAC MORPHOGENIC DEFECTS Principal Investigator & Institution: Chien, Kenneth R.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-JAN-2004 Summary: Vitamin A and its metabolites (retinoids) play a critical role in cardiac morphogenesis. Retinoids are potent human teratogens linked to several types of birth defects, including cardiovascular anomalies, while vitamin A deficiency can produce ventricular chamber hypoplasia, ventricular septal defects, and aortic abnormalities. A mutation in a single members of the retinoid receptor family (RCRalpha) reproduces many of the cardiovascular defects seen in vitamin A deficient embryos. The specific aims of the present proposal will capitalize on recent advances in CRE- lox technology ti specifically mutate the RXRalpha gene within specific cardiovascular cell type compartments during in vivo cardiac development: 1) to determine the role of RXRalpha pathways within atrial and ventricular muscle cells in control of cardiovascular morphogenesis by creating mice which harbor an early, complete atrial and ventricular muscle cell lineage restricted deficiency in RXRalpha via CRE-lox technology; 2) to determine the role of RXRalpha pathways within cardiac neural crest cell lineages in the control of cardiovascular morphogenesis by creating embryos which harbor a neural crest cell lineage restricted deficiency in RXRalpha; 3) To determine the role of RXRalpha pathways within endothelial/endocardial cushion cell lineages in cardiovascular morphogenesis by creating mice which harbor an endothelial cell lineage restricted deficiency in RXRalpha; 4) To determine the role of all retinoid receptor dependent pathways in specific cardiovascular cell types (atrial muscle, ventricular muscle, endothelial, and neural crest) in cardiovascular morphogenesis by creating mice which conditionally express a dominant negative retinoid receptor in specific cardiovascular cell types via a Cre-lox switch strategy. These studies should lead to the definitive identification of the specific cardiovascular cell types that generate the RXRalpha dependent signals required for specific steps in cardiac morphogenesis. Since mutations in a number of transcription factors have been implicated in human congenital heart defects, these studies of RXRalpha could lead to establishment of a new paradigm by which an individual transcription factor may be required in distinct cardiovascular cell types at precise stages of cardiogenesis to provide the molecular cues that lead to complex steps of cardiac morphogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: WINGED HELIX FACTORS IN EMBRYONIC DEVELOPMENT Principal Investigator & Institution: Hackett, Brian P.; Assistant Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: Congenital birth defects are one of the lading causes of neonatal morbidity and mortality. Human heterotaxy syndromes, such as Kartagener syndrome, often have associated lethal cardiac defects and defects in ciliary structure and function. Understanding the origins of these defects requires an elucidation of the mechanisms underlying the normal development of the embryo. Winged helix transcription factors play important roles during development by regulating cellular differentiation and cell specific gene expression. Hepatocyte nuclear factor/forkhead homologue (HFH) - 4 is a member of the winged helix family expressed during development in a variety of epithelial tissues. Mice homozygous for disruption of the hfh-4 gene have congenital abnormalities of the left-right axis asymmetry and lack cilia. HFH-4 is thus essential for determination of left-right axis asymmetry and ciliated cell differentiation during development. In the proposed studies, we will begin to elucidate the mechanisms of leftright asymmetry determination and ciliated epithelial cell differentiation by HFH-4. To begin to understand the genetic pathways involved in left-right asymmetry the early embryonic pattern of HFH-4 expression will be determined and the expression patterns of other ~left-right~ genes will be studied in hfh-4 mice. The structure of ciliated epithelium in hfh-4 mice will be studied by electron microscopy, as well as determination of the expression of genes associated with ciliated cell differentiation. Differential display will be used to identify potential target genes for HFH-4. The human HFH-4 gene will be isolated and characterized and single chain conformation polymorphism analysis used to identify mutations in the human HFH-4 gene. Elucidating the cellular and molecular mechanisms regulating the determination of leftright asymmetry has great significance for vertebrate development and the pathology of human congenital malformations. Insights into the differentiation of ciliated cells have important implications for understanding the respiratory function and pathology and for reproductive function and infertility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “birth defects” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for birth defects in the PubMed Central database:

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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The New Dysmorphology: Application of Insights from Basic Developmental Biology to the Understanding of Human Birth Defects. by Epstein CJ.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41007

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

A base-line survey on birth defects in Gansu province, West China. Author(s): Cheng N, Bai Y, Hu X, Pei H, Li Y, Zhang W, Fan X, Zhang P, Zhou X, Chen Z, Li C, He P, He H. Source: Annals of Tropical Paediatrics. 2003 March; 23(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648321&dopt=Abstract

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A case-control study of paternal smoking and birth defects. Author(s): Zhang J, Savitz DA, Schwingl PJ, Cai WW. Source: International Journal of Epidemiology. 1992 April; 21(2): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1428480&dopt=Abstract

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A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. Author(s): Brody LC, Conley M, Cox C, Kirke PN, McKeever MP, Mills JL, Molloy AM, O'Leary VB, Parle-McDermott A, Scott JM, Swanson DA. Source: American Journal of Human Genetics. 2002 November; 71(5): 1207-15. Epub 2002 October 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384833&dopt=Abstract

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

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A population-based birth defects surveillance system in the People's Republic of China. Author(s): Li S, Moore CA, Li Z, Berry RJ, Gindler J, Hong SX, Liu Y, Mulinare J, Wong LY, Gu HQ, Erickson JD. Source: Paediatric and Perinatal Epidemiology. 2003 July; 17(3): 287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839541&dopt=Abstract

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A rapid evolution mechanism may contribute to changes in sex ratio, multiple birth incidence, frequency of auto-immune disease and frequency of birth defects in Clomid conceptions. Author(s): Fischer K. Source: Medical Hypotheses. 1990 January; 31(1): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2314324&dopt=Abstract

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A review of studies on maternal occupational exposures and birth defects, and the limitations associated with these studies. Author(s): Shi L, Chia SE. Source: Occupational Medicine (Oxford, England). 2001 June; 51(4): 230-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463868&dopt=Abstract

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Absence of birth defects in offspring of women treated with dactinomycin. Author(s): Byrne J, Nicholson HS, Mulvihill JJ. Source: The New England Journal of Medicine. 1992 January 9; 326(2): 137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1727228&dopt=Abstract

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Active surveillance of birth defects among U.S. Department of Defense beneficiaries: a feasibility study. Author(s): Bush RA, Smith TC, Honner WK, Gray GC. Source: Military Medicine. 2001 February; 166(2): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272718&dopt=Abstract

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Additional information from parental questionnaires and pharmacy records for registration of birth defects. EuroMAP-group. Author(s): Reefhuis J, de Walle HE, de Jong-van den Berg LT, Cornel MC. Source: European Journal of Epidemiology. 2000 April; 16(4): 329-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959940&dopt=Abstract

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Addressing environmentally caused human birth defects. Author(s): Brent RL. Source: Pediatrics in Review / American Academy of Pediatrics. 2001 May; 22(5): 15365. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331737&dopt=Abstract

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ADH2 and CYP2E1 genetic polymorphisms: risk factors for alcohol-related birth defects. Author(s): McCarver DG. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 April; 29(4 Pt 2): 562-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259352&dopt=Abstract

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Alcohol-related birth defects. Minnesota's response to a critical health problem. Author(s): Leonard BJ, Boettcher LM, Brust JD. Source: Minn Med. 1991 December; 74(12): 23-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1791813&dopt=Abstract

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Alcohol-related birth defects--the past, present, and future. Author(s): Warren KR, Foudin LL. Source: Alcohol Research & Health : the Journal of the National Institute on Alcohol Abuse and Alcoholism. 2001; 25(3): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810952&dopt=Abstract

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Ambient air pollution and risk of birth defects in Southern California. Author(s): Ritz B, Yu F, Fruin S, Chapa G, Shaw GM, Harris JA. Source: American Journal of Epidemiology. 2002 January 1; 155(1): 17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772780&dopt=Abstract

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An instructional program for teaching adolescents approaches to the prevention of birth defects. Author(s): Fomby BL, Sterling Y. Source: J Natl Black Nurses Assoc. 1990 Spring-Summer; 4(2): 18-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2134694&dopt=Abstract

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Ancient records of birth defects. Author(s): Philipp EE. Source: Journal of the Royal Society of Medicine. 2000 June; 93(6): 336. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10911842&dopt=Abstract

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Ascertainment of birth defects: the effect on completeness of adding a new source of data. Author(s): Bower C, Silva D, Henderson TR, Ryan A, Rudy E. Source: Journal of Paediatrics and Child Health. 2000 December; 36(6): 574-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115034&dopt=Abstract

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Ascertainment of pregnancies terminated because of birth defects: effect on completeness of adding a new source of data. Author(s): Bower C, Ryan A, Rudy E. Source: Teratology. 2001 January; 63(1): 23-5. Erratum In: Teratology 2001 March; 63(3): 164. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11169551&dopt=Abstract

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Asian-American cultural perspectives on birth defects: focus on cleft palate. Author(s): Cheng LR. Source: Cleft Palate J. 1990 July; 27(3): 294-300. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2197040&dopt=Abstract

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Assessment of student pharmacists' knowledge concerning folic acid and prevention of birth defects demonstrates a need for further education. Author(s): Lynch SM. Source: The Journal of Nutrition. 2002 March; 132(3): 439-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880568&dopt=Abstract

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Bad air and birth defects. Author(s): Renner R. Source: Environmental Health Perspectives. 2002 June; 110(6): A291. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087981&dopt=Abstract

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Bendectin and birth defects. II: Ecological analyses. Author(s): Kutcher JS, Engle A, Firth J, Lamm SH. Source: Birth Defects Research. Part A, Clinical and Molecular Teratology. 2003 February; 67(2): 88-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769504&dopt=Abstract

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Bendectin and birth defects: hopefully, the final chapter. Author(s): Brent R. Source: Birth Defects Research. Part A, Clinical and Molecular Teratology. 2003 February; 67(2): 79-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769503&dopt=Abstract

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Bendectin--birth defects controversy. Author(s): Newman SA. Source: Jama : the Journal of the American Medical Association. 1990 August 1; 264(5): 569-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2366291&dopt=Abstract

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Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Author(s): Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR, Koren G. Source: Teratology. 2000 December; 62(6): 385-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11091360&dopt=Abstract

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Birth defects among children born to a population occupationally exposed to pesticides in Colombia. Author(s): Restrepo M, Munoz N, Day N, Parra JE, Hernandez C, Blettner M, Giraldo A. Source: Scand J Work Environ Health. 1990 August; 16(4): 239-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2389130&dopt=Abstract

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Birth defects among offspring of firemen. Author(s): Olshan AF, Teschke K, Baird PA. Source: American Journal of Epidemiology. 1990 February; 131(2): 312-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2296983&dopt=Abstract

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Birth defects and paternal occupational exposure. Hypotheses tested in a record linkage based dataset. Author(s): Irgens A, Kruger K, Skorve AH, Irgens LM. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2000 June; 79(6): 465-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857870&dopt=Abstract

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Birth defects in aborigines. Author(s): Lancaster PA. Source: The Medical Journal of Australia. 1989 September 4; 151(5): 241-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2770598&dopt=Abstract

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Birth defects in children with newborn encephalopathy. Author(s): Felix JF, Badawi N, Kurinczuk JJ, Bower C, Keogh JM, Pemberton PJ. Source: Developmental Medicine and Child Neurology. 2000 December; 42(12): 803-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11132253&dopt=Abstract

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Birth defects in Norway by levels of external and food-based exposure to radiation from Chernobyl. Author(s): Lie RT, Irgens LM, Skjaerven R, Reitan JB, Strand P, Strand T. Source: American Journal of Epidemiology. 1992 August 15; 136(4): 377-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415157&dopt=Abstract

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Birth defects in the infants of aboriginal and non-aboriginal mothers with diabetes in Western Australia. Author(s): Bower C, Stanley F, Connell AF, Gent CR, Massey MS. Source: The Medical Journal of Australia. 1992 April 20; 156(8): 520-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1565042&dopt=Abstract

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Birth defects in twins: study in a Spanish population. Author(s): Ramos-Arroyo MA. Source: Acta Genet Med Gemellol (Roma). 1991; 40(3-4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1821510&dopt=Abstract

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Birth defects monitoring in California: a resource for epidemiological research. Author(s): Croen LA, Shaw GM, Jensvold NG, Harris JA. Source: Paediatric and Perinatal Epidemiology. 1991 October; 5(4): 423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1754501&dopt=Abstract

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Birth defects prevalence among infants of Persian Gulf War veterans born in Hawaii, 1989-1993. Author(s): Araneta MR, Destiche DA, Schlangen KM, Merz RD, Forrester MB, Gray GC. Source: Teratology. 2000 October; 62(4): 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992261&dopt=Abstract

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Birth defects surveillance data from selected states, 1995-1999. Author(s): National Center on Birth Defects and Developmental Disabilities, CDC. Source: Teratology. 2002; 66 Suppl 1: S129-211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239747&dopt=Abstract

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Birth defects surveillance. Author(s): Smulian JC, Beres-Sochka L, DePrince K, Canterino J, Fischer R, Apuzzio J, Royle M. Source: N J Med. 2002 December; 99(12): 25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510570&dopt=Abstract

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Birth defects surveillance. A pilot system in the Cape Peninsula. Author(s): Sayed AR, Bourne DE, Nixon JM, Klopper JM, Op't Hof J. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1989 July 1; 76(1): 5-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2740960&dopt=Abstract

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Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA. Author(s): Garry VF, Harkins ME, Erickson LL, Long-Simpson LK, Holland SE, Burroughs BL. Source: Environmental Health Perspectives. 2002 June; 110 Suppl 3: 441-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060842&dopt=Abstract

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Birth defects: traditional explanations of causation recalled by medical and dental students in Papua New Guinea at the commencement of their preclinical education. Author(s): Dryden R. Source: P N G Med J. 1990 September; 33(3): 207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2080671&dopt=Abstract

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Can birth defects be prevented? Author(s): Dryden R. Source: P N G Med J. 1997 March; 40(1): 1-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10365564&dopt=Abstract

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Can maternal risk factors influence the presence of major birth defects in infants with Down syndrome? Author(s): Khoury MJ, Erickson JD. Source: American Journal of Medical Genetics. 1992 August 1; 43(6): 1016-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415327&dopt=Abstract

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Cardiovascular birth defects and prenatal exposure to female sex hormones: a reevaluation of data reanalysis from a large prospective study. Author(s): Hook EB. Source: Teratology. 1992 September; 46(3): 261-6. Corrected and Republished In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1523583&dopt=Abstract

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Case-crossover and case-time-control designs in birth defects epidemiology. Author(s): Hernandez-Diaz S, Hernan MA, Meyer K, Werler MM, Mitchell AA. Source: American Journal of Epidemiology. 2003 August 15; 158(4): 385-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915504&dopt=Abstract

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Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Author(s): Hernan MA, Hernandez-Diaz S, Werler MM, Mitchell AA. Source: American Journal of Epidemiology. 2002 January 15; 155(2): 176-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790682&dopt=Abstract

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Central nervous system congenital malformations, especially neural tube defects in 29 provinces, metropolitan cities and autonomous regions of China: Chinese Birth Defects Monitoring Program. Author(s): Xiao KZ, Zhang ZY, Su YM, Liu FQ, Yan ZZ, Jiang ZQ, Zhou SF, He WG, Wang BY, Jiang HP, et al. Source: International Journal of Epidemiology. 1990 December; 19(4): 978-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2084031&dopt=Abstract

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Chorionic Villus Sampling Birth Defects Registry. Author(s): McGuirk C. Source: Plastic and Reconstructive Surgery. 1999 September; 104(4): 1213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10654783&dopt=Abstract

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Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy. Author(s): Khoury MJ, Becerra JE, Cordero JF, Erickson JD. Source: Pediatrics. 1989 October; 84(4): 658-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2674881&dopt=Abstract

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Clusters of birth defects: emergency and management. A review of some publications. Author(s): Goujard J. Source: European Journal of Epidemiology. 1999 October; 15(9): 853-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608366&dopt=Abstract

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Coeliac disease and birth defects in offspring. Author(s): Hozyasz KK. Source: Gut. 2001 November; 49(5): 738. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693118&dopt=Abstract

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Collecting and interpreting birth defects surveillance data by hispanic ethnicity: a comparative study. The Hispanic Ethnicity Birth Defects Workgroup. Author(s): Kirby R, Petrini J, Alter C. Source: Teratology. 2000 January-February; 61(1-2): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603199&dopt=Abstract

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Comments: on “rates” of birth defects. Author(s): Hexter AC. Source: Teratology. 1990 April; 41(4): 473-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2339324&dopt=Abstract

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Completeness of the discharge diagnoses as a measure of birth defects recorded in the hospital birth record. Author(s): Calle EE, Khoury MJ. Source: American Journal of Epidemiology. 1991 July 1; 134(1): 69-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1853862&dopt=Abstract

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Consanguinity and birth defects. Author(s): Connon AF, Haan E. Source: The Medical Journal of Australia. 1989 February 6; 150(3): 168. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2716596&dopt=Abstract

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Consanguinity and recurrence risk of birth defects: a population-based study. Author(s): Stoltenberg C, Magnus P, Skrondal A, Lie RT. Source: American Journal of Medical Genetics. 1999 February 19; 82(5): 423-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10069715&dopt=Abstract

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Contribution of birth defects to infant mortality among racial/ethnic minority groups, United States, 1983. Author(s): Lynberg MC, Khoury MJ. Source: Mmwr. Cdc Surveillance Summaries : Morbidity and Mortality Weekly Report. Cdc Surveillance Summaries / Centers for Disease Control. 1990 July; 39(3): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2115106&dopt=Abstract

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Contribution of birth defects to infant mortality in the United States. Author(s): Petrini J, Damus K, Russell R, Poschman K, Davidoff MJ, Mattison D. Source: Teratology. 2002; 66 Suppl 1: S3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239736&dopt=Abstract

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Co-occurrence of developmental disabilities with birth defects. Author(s): Kirby RS. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2002; 8(3): 182-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12216062&dopt=Abstract

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Counterpoint: Responding to inadequate critique of birth defects paper. Author(s): Cowan DN, Gray GC, DeFraites RF. Source: American Journal of Epidemiology. 1998 August 15; 148(4): 326-7; Discussion 334-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9717874&dopt=Abstract

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Culture, health care, and birth defects in the United States: an introduction. Author(s): Strauss RP. Source: Cleft Palate J. 1990 July; 27(3): 275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2372976&dopt=Abstract

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Decrease birth defects by increasing the number of women who take folic acid before they are pregnant. Author(s): Nakamura P. Source: Alaska Med. 1999 July-September; 41(3): 73. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10540499&dopt=Abstract

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Deletions of human chromosome 22 and associated birth defects. Author(s): Scambler PJ. Source: Current Opinion in Genetics & Development. 1993 June; 3(3): 432-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8353418&dopt=Abstract

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Descriptive profile of birth defects among livebirths in Singapore. Author(s): Thein MM, Koh D, Tan KL, Lee HP, Yip YY, Tye CY, Phoon WO. Source: Teratology. 1992 September; 46(3): 277-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1523586&dopt=Abstract

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Detection of genotype-environment interaction in case-control studies of birth defects: how big a sample size? Author(s): Khoury MJ, Beaty TH, Hwang SJ. Source: Teratology. 1995 May; 51(5): 336-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7482355&dopt=Abstract

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Developing a birth defects registry for Tennessee. Author(s): Van Cleave ML. Source: J Tenn Med Assoc. 1994 February; 87(2): 60-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8176916&dopt=Abstract

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Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Author(s): Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Source: Pediatrics. 1990 January; 85(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2404255&dopt=Abstract

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Diagnostic approach to children with birth defects. Author(s): Pai GS, Gadewar SB. Source: Indian J Pediatr. 2000 November; 67(11): 819-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216382&dopt=Abstract

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Disorganization in mice and humans and its relation to sporadic birth defects. Author(s): Robin NH, Abbadi N, McCandless SE, Nadeau JH. Source: American Journal of Medical Genetics. 1997 December 31; 73(4): 425-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415470&dopt=Abstract

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DNA oxidation as a potential molecular mechanism mediating drug-induced birth defects: phenytoin and structurally related teratogens initiate the formation of 8hydroxy-2'-deoxyguanosine in vitro and in vivo in murine maternal hepatic and embryonic tissues. Author(s): Liu L, Wells PG. Source: Free Radical Biology & Medicine. 1995 November; 19(5): 639-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8529923&dopt=Abstract

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Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Author(s): Correa A, Botto L, Liu Y, Mulinare J, Erickson JD. Source: Pediatrics. 2003 May; 111(5 Part 2): 1146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728128&dopt=Abstract

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Does ascertainment bias contribute to the reported association of omphalocele and gastroschisis with other birth defects in families but not in individuals? Author(s): Hook EB. Source: American Journal of Medical Genetics. 1993 September 1; 47(3): 435-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8135295&dopt=Abstract

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Does cocaine cause birth defects? Author(s): Church MW. Source: Neurotoxicology and Teratology. 1993 September-October; 15(5): 289; Discussion 311-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8277916&dopt=Abstract

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Does periconceptional multivitamin use reduce the risk of neural tube defects associated with other birth defects? Author(s): Bower C, Stanley FJ. Source: American Journal of Medical Genetics. 1997 May 16; 70(2): 206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9128944&dopt=Abstract

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Does periconceptional multivitamin use reduce the risk of neural tube defects associated with other birth defects? data from two population-based case-control studies. Author(s): Khoury MJ, Shaw GM, Moore CA, Lammer EJ, Mulinare J. Source: American Journal of Medical Genetics. 1996 January 2; 61(1): 30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8741914&dopt=Abstract

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Does thalidomide cause second generation birth defects? Author(s): Smithells D. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1998 November; 19(5): 339-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825947&dopt=Abstract

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Dose response relationship between adriamycin and birth defects in a rat model of VATER association. Author(s): Orford JE, Cass DT. Source: Journal of Pediatric Surgery. 1999 March; 34(3): 392-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211639&dopt=Abstract

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Dr. Biswas not responsible for birth defects. Author(s): Hunt JA. Source: W V Med J. 1990 May; 86(5): 215-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2360324&dopt=Abstract

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Drinking patterns and alcohol-related birth defects. Author(s): Maier SE, West JR. Source: Alcohol Research & Health : the Journal of the National Institute on Alcohol Abuse and Alcoholism. 2001; 25(3): 168-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810954&dopt=Abstract

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Drugs of choice in pregnancy: primary prevention of birth defects. Author(s): Peters PW, Garbis-Berkvens HM, Bannigan JG. Source: Reproductive Toxicology (Elmsford, N.Y.). 1993 September-October; 7(5): 399404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8274815&dopt=Abstract

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Dursban revisited: birth defects, U.S. Environmental Protection Agency, and Centers for Disease Control. Author(s): Sherman JD. Source: Archives of Environmental Health. 1997 September-October; 52(5): 332-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9546754&dopt=Abstract

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Early childhood surveillance of developmental disorders by a birth defects surveillance system: methods, prevalence comparisons, and mortality patterns. Author(s): Kirby RS, Brewster MA, Canino CU, Pavin M. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 1995 October; 16(5): 318-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8557831&dopt=Abstract

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Effect of prenatal diagnosis on epidemiologic studies of birth defects. Author(s): Cragan JD, Khoury MJ. Source: Epidemiology (Cambridge, Mass.). 2000 November; 11(6): 695-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055632&dopt=Abstract

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Effective coding in birth defects surveillance. Author(s): Rasmussen SA, Moore CA. Source: Teratology. 2001; 64 Suppl 1: S3-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745837&dopt=Abstract

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Effects of craniofacial birth defects on maternal functioning postinfancy. Author(s): Speltz ML, Armsden GC, Clarren SS. Source: Journal of Pediatric Psychology. 1990 April; 15(2): 177-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2374074&dopt=Abstract

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Elevated birth defects in racial or ethnic minority children of women living near hazardous waste sites. Author(s): Orr M, Bove F, Kaye W, Stone M. Source: International Journal of Hygiene and Environmental Health. 2002 March; 205(12): 19-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018013&dopt=Abstract

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Emotional correlates and consequences of birth defects. Author(s): Nolan T, Pless IB. Source: The Journal of Pediatrics. 1986 July; 109(1): 201-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3522837&dopt=Abstract

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Epidemiologic methods in the search for causes of human birth defects. Author(s): Ferencz C, Loffredo C, Wilson PD. Source: Teratology. 2000 April; 61(4): 243-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716741&dopt=Abstract

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Epidemiology of birth defects. Author(s): Khoury MJ. Source: Epidemiologic Reviews. 1989; 11: 244-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2680559&dopt=Abstract

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Epidemiology of birth defects. Author(s): Janerich DT, Polednak AP. Source: Epidemiologic Reviews. 1983; 5: 16-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6357820&dopt=Abstract

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Epidemiology of sentinel birth defects in Maryland, 1984. Author(s): Khoury MJ, Weinstein A, Panny SR, Holtzman NA, Lindsay PK, Warthen FJ, Street NA, Robertson MO, Farrell KP, Eisenberg M. Source: Md Med J. 1986 October; 35(10): 837-45. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3784799&dopt=Abstract

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Epigenetic alterations of H19 and LIT1 distinguish patients with BeckwithWiedemann syndrome with cancer and birth defects. Author(s): DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP. Source: American Journal of Human Genetics. 2002 March; 70(3): 604-11. Epub 2002 January 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813134&dopt=Abstract

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Estimates of the economic costs of birth defects. Author(s): Waitzman NJ, Romano PS, Scheffler RM. Source: Inquiry. 1994 Summer; 31(2): 188-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8021024&dopt=Abstract

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Ethical issues surrounding the treatment of newborns with birth defects. Author(s): Ahluwalia JS. Source: J La State Med Soc. 1986 June; 138(6): 33-4, 39-40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3734757&dopt=Abstract

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Evaluating false positives in two hospital discharge data sets of the Birth Defects Monitoring Program. Author(s): Callif-Daley FA, Huether CA, Edmonds LD. Source: Public Health Reports (Washington, D.C. : 1974). 1995 March-April; 110(2): 15460. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7630991&dopt=Abstract

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Evaluation of the association between birth defects and exposure to ambient vinyl chloride. Author(s): Theriault G, Iturra H, Gingras S. Source: Teratology. 1983 June; 27(3): 359-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6879459&dopt=Abstract

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Evaluation of the Birth Defects Monitoring Program, 1982-1985. Author(s): Lynberg MC, Chavez GF, Edmonds LD, Mulinare J. Source: Teratology. 1993 December; 48(6): 650-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8115974&dopt=Abstract

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Evaluation of the hospital discharge diagnoses index and the birth certificate as sources of information on birth defects. Author(s): Hexter AC, Harris JA, Roeper P, Croen LA, Krueger P, Gant D. Source: Public Health Reports (Washington, D.C. : 1974). 1990 May-June; 105(3): 296-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2113690&dopt=Abstract

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Exogenous female sex hormones and birth defects. Author(s): Polednak AP. Source: Public Health Rev. 1985; 13(1-2): 89-114. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2939493&dopt=Abstract

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Exposure assessment in epidemiologic studies of birth defects by industrial hygiene review of maternal interviews. Author(s): Katz EA, Shaw GM, Schaffer DM. Source: American Journal of Industrial Medicine. 1994 July; 26(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8074117&dopt=Abstract

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Exposure to mesalamine during pregnancy increased preterm deliveries (but not birth defects) and decreased birth weight. Author(s): Sachar D. Source: Gut. 1998 September; 43(3): 316. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9863473&dopt=Abstract

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Failure to inform of AFP test: birth defects--$4.3 million damages. Case in point: Basten by and through Basten v. U.S. 848 F. Supp. 2d 962 AL (1994). Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1994 July; 35(2): 2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7520591&dopt=Abstract

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Families with birth defects: is birth weight of nonmalformed siblings affected? Author(s): Melve KK, Skjaerven R. Source: American Journal of Epidemiology. 2002 May 15; 155(10): 932-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994233&dopt=Abstract

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Fertilisation involving ageing gametes, major birth defects, and Down's syndrome. Author(s): Simpson JL, Gray R, Perez A, Mena P, Queenan JT, Barbato M, Pardo F, Kambic R, Jennings V. Source: Lancet. 2002 May 11; 359(9318): 1670-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020531&dopt=Abstract

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Fetal alcohol syndrome and other alcohol-related birth defects. Author(s): McCarthy PA. Source: The Nurse Practitioner. 1983 January; 8(1): 33-4, 37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6828263&dopt=Abstract

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Fetal deaths with birth defects among Japanese multiples, 1974. Author(s): Imaizumi Y, Asaka A, Inouye E. Source: Acta Genet Med Gemellol (Roma). 1990; 39(3): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2085071&dopt=Abstract

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Finding the causes of birth defects. Author(s): Cordero JF. Source: The New England Journal of Medicine. 1994 July 7; 331(1): 48-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8202104&dopt=Abstract

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Flawed epidemiology of birth defects? Author(s): Lie RT. Source: Lancet. 1995 October 14; 346(8981): 1037. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7475570&dopt=Abstract

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Folate fortification for the prevention of birth defects: case study. Author(s): Feinleib M, Beresford SA, Bowman BA, Mills JL, Rader JI, Selhub J, Yetley EA. Source: American Journal of Epidemiology. 2001 December 15; 154(12 Suppl): S60-9. Review. Erratum In: Am J Epidemiol 2002 January 15; 155(2): 189. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744531&dopt=Abstract

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Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. Author(s): Refsum H. Source: The British Journal of Nutrition. 2001 May; 85 Suppl 2: S109-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509098&dopt=Abstract

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Folic acid and prevention of birth defects. Author(s): Van Dyke DC, Stumbo PJ, Mary JB, Niebyl JR. Source: Developmental Medicine and Child Neurology. 2002 June; 44(6): 426-9. Review. Erratum In: Dev Med Child Neurol. 2003 May; 45(5): 360. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088312&dopt=Abstract

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Folic acid and prevention of birth defects. Author(s): Czeizel AE. Source: Jama : the Journal of the American Medical Association. 1996 June 5; 275(21): 1635-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8637131&dopt=Abstract

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Folic acid and the prevention of birth defects. Author(s): Butterworth CE Jr, Bendich A. Source: Annual Review of Nutrition. 1996; 16: 73-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8839920&dopt=Abstract

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Folic acid antagonists during pregnancy and risk of birth defects. Author(s): Newman RD, Parise M, Nahlen B. Source: The New England Journal of Medicine. 2001 March 22; 344(12): 934; Author Reply 934-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263427&dopt=Abstract

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Folic acid antagonists during pregnancy and risk of birth defects. Author(s): Sharfstein JM. Source: The New England Journal of Medicine. 2001 March 22; 344(12): 933; Author Reply 934-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263426&dopt=Abstract

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Folic acid antagonists during pregnancy and risk of birth defects. Author(s): Amitai Y, Leventhal A. Source: The New England Journal of Medicine. 2001 March 22; 344(12): 933; Author Reply 934-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263425&dopt=Abstract

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Folic acid antagonists during pregnancy and risk of birth defects. Author(s): Brentlinger PE. Source: The New England Journal of Medicine. 2001 March 22; 344(12): 933-4; Author Reply 934-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263424&dopt=Abstract

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Folic acid antagonists during pregnancy and the risk of birth defects. Author(s): Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Source: The New England Journal of Medicine. 2000 November 30; 343(22): 1608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096168&dopt=Abstract

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Folic acid in the prevention of birth defects. Author(s): Allen WP. Source: Current Opinion in Pediatrics. 1996 December; 8(6): 630-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9018449&dopt=Abstract

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Folic acid supplementation and prevention of birth defects. Author(s): Green NS. Source: The Journal of Nutrition. 2002 August; 132(8 Suppl): 2356S-2360S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163692&dopt=Abstract

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Frequency of prenatal diagnosis of birth defects in Houston, Galveston and the Lower Rio Grande Valley, Texas 1995. Author(s): Waller DK, Pujazon MA, Canfield MA, Scheuerle AE, Byrne JL. Source: Fetal Diagnosis and Therapy. 2000 November-December; 15(6): 348-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111216&dopt=Abstract

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Genetic control of drug metabolism: relationship to birth defects. Author(s): Nebert DW, Bigelow SW. Source: Semin Perinatol. 1982 April; 6(2): 105-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7048534&dopt=Abstract

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Genetic counseling for patients with birth defects. Author(s): Aylsworth AS. Source: Pediatric Clinics of North America. 1992 April; 39(2): 229-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1553242&dopt=Abstract

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Genetic epidemiology of birth defects: nonsyndromic cleft lip and neural tube defects. Author(s): Mitchell LE. Source: Epidemiologic Reviews. 1997; 19(1): 61-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9360903&dopt=Abstract

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Genetic predisposition to phenytoin-induced birth defects. Author(s): Strickler SM, Dansky LV, Miller MA, Seni MH, Andermann E, Spielberg SP. Source: Lancet. 1985 October 5; 2(8458): 746-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2864485&dopt=Abstract

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Genetic susceptibility to birth defects in humans: from gene discovery to public health action. Author(s): Khoury MJ. Source: Teratology. 2000 January-February; 61(1-2): 17-20. Erratum In: Teratology 2000 April; 61(4): 318. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603198&dopt=Abstract

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Good news and bad for women with birth defects. Author(s): Golding J. Source: The New England Journal of Medicine. 1999 April 8; 340(14): 1108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194242&dopt=Abstract

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Good news for women and babies: folic acid prevents birth defects. Author(s): Havens DH, Levin BR. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 1999 September-October; 13(5): 255-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776204&dopt=Abstract

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Guidelines for case classification for the National Birth Defects Prevention Study. Author(s): Rasmussen SA, Olney RS, Holmes LB, Lin AE, Keppler-Noreuil KM, Moore CA; National Birth Defects Prevention Study. Source: Birth Defects Research. Part A, Clinical and Molecular Teratology. 2003 March; 67(3): 193-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797461&dopt=Abstract

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Handling surveillance types of data on birth defects and exposures during pregnancy. Author(s): Robert E. Source: Reproductive Toxicology (Elmsford, N.Y.). 1992; 6(3): 205-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591477&dopt=Abstract

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Herbicide claimed responsible for birth defects. Author(s): Dickson D. Source: Nature. 1979 November; 282(5736): 220. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=503197&dopt=Abstract

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Heterogeneous rates for birth defects in Latin America: hints on causality. Author(s): Lopez-Camelo JS, Orioli IM. Source: Genetic Epidemiology. 1996; 13(5): 469-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8905393&dopt=Abstract

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Honeybee syndrome, glycolysis, and birth defects (continued) Author(s): Adams MJ Jr. Source: The New England Journal of Medicine. 1984 September 27; 311(13): 860. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6472392&dopt=Abstract

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How folate can help prevent birth defects. Author(s): Mazza D. Source: Aust Fam Physician. 1999 July; 28(7): 719. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10431431&dopt=Abstract

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Hyperthermia and birth defects. Author(s): Edwards MJ, Shiota K, Smith MS, Walsh DA. Source: Reproductive Toxicology (Elmsford, N.Y.). 1995 September-October; 9(5): 41125. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8563185&dopt=Abstract

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Hyperthermia and birth defects. Author(s): Edwards MJ. Source: Cornell Vet. 1993 January; 83(1): 1-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8417850&dopt=Abstract

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Hypoplastic right-sided heart complex: a cluster of cases with associated congenital birth defects. A new syndrome? Author(s): Baetz-Greenwalt B, Ratliff NB, Moodie DS. Source: The Journal of Pediatrics. 1983 September; 103(3): 399-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6886905&dopt=Abstract

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Hypothesis: prenatal ethanol-induced birth defects and retinoic acid. Author(s): Pullarkat RK. Source: Alcoholism, Clinical and Experimental Research. 1991 June; 15(3): 565-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1877745&dopt=Abstract

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Hypothesis: the pathogenesis of the birth defects reported in cvs-exposed infants. Author(s): Kaufman MH. Source: Teratology. 1994 December; 50(6): 377-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7778041&dopt=Abstract

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Immunology and birth defects: introduction to special issue. Author(s): Clark DA. Source: Am J Reprod Immunol Microbiol. 1987 December; 15(4): 131-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3434664&dopt=Abstract

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Impact of an educational seminar on high school students' knowledge of folic acid supplementation and its role in the prevention of birth defects. Author(s): Johnson PA, Stadler DD, Feldkamp M, Webber B. Source: Journal of the American Dietetic Association. 2002 March; 102(3 Suppl): S78-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902395&dopt=Abstract

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Impact of prenatal diagnosis and elective termination on the prevalence of selected birth defects in Hawaii. Author(s): Forrester MB, Merz RD, Yoon PW. Source: American Journal of Epidemiology. 1998 December 15; 148(12): 1206-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9867267&dopt=Abstract

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Improving estimates of caregiver time cost and family impact associated with birth defects. Author(s): Tilford JM, Robbins JM, Hobbs CA. Source: Teratology. 2001; 64 Suppl 1: S37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745843&dopt=Abstract

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Incidence of birth defects after artificial insemination with frozen donor spermatozoa: a collaborative study of the French CECOS Federation on 11,535 pregnancies. Author(s): Thepot F, Mayaux MJ, Czyglick F, Wack T, Selva J, Jalbert P. Source: Human Reproduction (Oxford, England). 1996 October; 11(10): 2319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8943549&dopt=Abstract

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Incidence of birth defects. Author(s): Erickson RP. Source: American Journal of Human Genetics. 1987 February; 40(2): 184. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3565380&dopt=Abstract

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Inclusion of early fetal deaths in a birth defects surveillance system. Author(s): Forrester MB, Merz RD. Source: Teratology. 2001; 64 Suppl 1: S20-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745840&dopt=Abstract

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Increased risk for developmental disabilities in children who have major birth defects: a population-based study. Author(s): Decoufle P, Boyle CA, Paulozzi LJ, Lary JM. Source: Pediatrics. 2001 September; 108(3): 728-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533343&dopt=Abstract

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Increased vulnerability to alcohol-related birth defects in the offspring of mothers over 30. Author(s): Jacobson JL, Jacobson SW, Sokol RJ. Source: Alcoholism, Clinical and Experimental Research. 1996 April; 20(2): 359-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8730230&dopt=Abstract

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Information and education: valuable tools in prevention of birth defects. Author(s): Larsson KS. Source: Prog Clin Biol Res. 1985; 163C: 341-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3991641&dopt=Abstract

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Integrating birth defects surveillance in maternal and child health at the state level. Author(s): Klein Walker D. Source: Teratology. 2000 January-February; 61(1-2): 4-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10603196&dopt=Abstract

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Integration of DNA sample collection into a multi-site birth defects case-control study. Author(s): Rasmussen SA, Lammer EJ, Shaw GM, Finnell RH, McGehee RE Jr, Gallagher M, Romitti PA, Murray JC; National Birth Defects Prevention Study. Source: Teratology. 2002 October; 66(4): 177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353214&dopt=Abstract

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Interaction between epidemiology and laboratory sciences in the study of birth defects: design of birth defects risk factor surveillance in metropolitan Atlanta. Author(s): Lynberg MC, Khoury MJ. Source: Journal of Toxicology and Environmental Health. 1993 October-November; 40(23): 435-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8230314&dopt=Abstract

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Interrelationships of relative risks of birth defects in embryonic and fetal deaths, in livebirths, and in all conceptuses. Author(s): Regal RR, Hook EB. Source: Epidemiology (Cambridge, Mass.). 1992 May; 3(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591324&dopt=Abstract

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Introduction: birth defects surveillance in the United States. Author(s): Erickson JD. Source: Teratology. 1997 July-August; 56(1-2): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329161&dopt=Abstract

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Iodine 131 thyroid ablation in female children and adolescents: long-term risk of infertility and birth defects. Author(s): Smith MB, Xue H, Takahashi H, Cangir A, Andrassy RJ. Source: Annals of Surgical Oncology : the Official Journal of the Society of Surgical Oncology. 1994 March; 1(2): 128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7834437&dopt=Abstract

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Is my baby all right? Two controversial studies link a common prenatal test to birth defects. Author(s): Seligmann J, Whitmore J, Marszalek D, Friday C, Gordon J, Clifton T. Source: Newsweek. 1992 June 22; 119(25): 62-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10119139&dopt=Abstract

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Is prevention of all cardiovascular birth defects a feasible goal? Author(s): McNamara DG. Source: Heart Dis Stroke. 1992 July-August; 1(4): 176-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1344105&dopt=Abstract

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Is there a connection between pollution and birth defects? Author(s): Gold WS. Source: Tex Med. 1990 January; 86(1): 10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2300908&dopt=Abstract

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Is there a genetic relationship between epilepsy and birth defects? Author(s): Durner M, Greenberg DA, Delgado-Escueta AV. Source: Neurology. 1992 April; 42(4 Suppl 5): 63-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1574178&dopt=Abstract

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Kudos to the Food and Drug Administration: reversal of the package insert warning for birth defects for oral contraceptives. Author(s): Brent RL. Source: Teratology. 1989 January; 39(1): 93-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2718144&dopt=Abstract

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Laboratory screening for genetic disorders and birth defects. Author(s): Bamforth FJ. Source: Clinical Biochemistry. 1994 October; 27(5): 333-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7867213&dopt=Abstract

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Lack of birth defects after paternal exposure to lamivudine. Author(s): Trojan J, Kronenberger B, von Wagner M, Zeuzem S. Source: Journal of Hepatology. 2002 April; 36(4): 571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943434&dopt=Abstract

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Lack of birth defects among offspring conceived during or after paternal exposure to dibromochloropropane (DBCP). Author(s): Potashnik G, Phillip M. Source: Andrologia. 1988 January-February; 20(1): 90-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3369712&dopt=Abstract

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Laterality patterns in infants with external birth defects. Author(s): Paulozzi LJ, Lary JM. Source: Teratology. 1999 November; 60(5): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525204&dopt=Abstract

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Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. Author(s): Happle R. Source: Journal of the American Academy of Dermatology. 1987 April; 16(4): 899-906. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3033033&dopt=Abstract

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Letter: Birth defects among infants of nurse anesthetists. Author(s): Cote CJ. Source: Anesthesiology. 1975 April; 42(4): 514-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1119724&dopt=Abstract

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Letter: Birth defects and oestrogens and progesterones in pregnancy. Author(s): Harlap S, Prywes R, Davies AM. Source: Lancet. 1975 March 22; 1(7908): 682-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=47104&dopt=Abstract

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Letter: Birth defects and oral contraceptives. Author(s): Balci S, Say B, Pirnar T, Hicsonmez A. Source: Lancet. 1973 November 10; 2(7837): 1098. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4127366&dopt=Abstract

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Letter: Birth defects and oral hormone preparations. Author(s): David TJ, O'Callaghan SE. Source: Lancet. 1974 June 15; 1(7868): 1236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4134709&dopt=Abstract

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Letter: Epidemiology of birth defects. Author(s): Janerich DT. Source: Lancet. 1975 December 27; 2(7948): 1304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=54822&dopt=Abstract

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Leukocyte Enzymes in birth defects- a review. Author(s): Brewster MA. Source: Ann Clin Lab Sci. 1981 March-April; 11(2): 146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6455086&dopt=Abstract

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Limb defects associated with major congenital anomalies: clinical and epidemiological study from the International Clearinghouse for Birth Defects Monitoring Systems. Author(s): Rosano A, Botto LD, Olney RS, Khoury MJ, Ritvanen A, Goujard J, Stoll C, Cocchi G, Merlob P, Mutchinick O, Cornel MC, Castilla EE, Martinez-Frias ML, Zampino G, Erickson JD, Mastroiacovo P. Source: American Journal of Medical Genetics. 2000 July 17; 93(2): 110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869112&dopt=Abstract

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Major birth defects after assisted reproduction. Author(s): Sutcliffe AG, Bonduelle M, Taylor BW. Source: The New England Journal of Medicine. 2002 October 31; 347(18): 1449-51; Author Reply 1449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418038&dopt=Abstract

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Major birth defects after assisted reproduction. Author(s): Sills ES, Palermo GD. Source: The New England Journal of Medicine. 2002 October 31; 347(18): 1449-51; Author Reply 1449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418037&dopt=Abstract

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Major birth defects after assisted reproduction. Author(s): Steinkampf MP, Grifo J. Source: The New England Journal of Medicine. 2002 October 31; 347(18): 1449-51; Author Reply 1449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409552&dopt=Abstract

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Major birth defects among infants with Down syndrome in Alexandria, Egypt (19952000): trends and risk factors. Author(s): Mokhtar MM, Abdel-Fattah M. Source: East Mediterr Health J. 2001 May; 7(3): 441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690765&dopt=Abstract

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Major birth defects among infants with Down's syndrome in Alexandria, Egypt (19952000). Author(s): Mokhtar MM, Abdel-Fattah M. Source: Journal of Tropical Pediatrics. 2002 August; 48(4): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200989&dopt=Abstract

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Major birth defects in very low birth weight infants in the Vermont Oxford Network. Author(s): Suresh GK, Horbar JD, Kenny M, Carpenter JH; Vermont Oxford Network. Source: The Journal of Pediatrics. 2001 September; 139(3): 366-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562615&dopt=Abstract

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Maternal age and birth defects: a population study. Author(s): Baird PA, Sadovnick AD, Yee IM. Source: Lancet. 1991 March 2; 337(8740): 527-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1671898&dopt=Abstract

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Maternal alcohol use in relation to selected birth defects. Author(s): Werler MM, Lammer EJ, Rosenberg L, Mitchell AA. Source: American Journal of Epidemiology. 1991 October 1; 134(7): 691-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1951274&dopt=Abstract

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Maternal diabetes and its cell membrane abnormalities as they affect the foetus: implications for the mother and birth defects. Author(s): Lowy C. Source: Nutr Health. 2001; 15(3-4): 245-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003091&dopt=Abstract

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Maternal diabetes: the risk for specific birth defects. Author(s): Ramos-Arroyo MA, Rodriguez-Pinilla E, Cordero JF. Source: European Journal of Epidemiology. 1992 July; 8(4): 503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1397216&dopt=Abstract

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Maternal fever, multivitamin use, and selected birth defects: evidence of interaction? Author(s): Botto LD, Erickson JD, Mulinare J, Lynberg MC, Liu Y. Source: Epidemiology (Cambridge, Mass.). 2002 July; 13(4): 485-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094106&dopt=Abstract

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Maternal obesity and risk for birth defects. Author(s): Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA. Source: Pediatrics. 2003 May; 111(5 Part 2): 1152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728129&dopt=Abstract

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Maternal smoking and birth defects: validity of birth certificate data for effect estimation. Author(s): Honein MA, Paulozzi LJ, Watkins ML. Source: Public Health Reports (Washington, D.C. : 1974). 2001 July-August; 116(4): 32735. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037261&dopt=Abstract

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Maternal smoking and congenital birth defects. Author(s): Morgan TM. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 January-February; 15(1): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841147&dopt=Abstract

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Maternal smoking and the risk of congenital birth defects: a cohort study. Author(s): Woods SE, Raju U. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2001 September-October; 14(5): 330-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572537&dopt=Abstract

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Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study. Author(s): Khoury MJ, Becerra JE, d'Almada PJ. Source: Paediatric and Perinatal Epidemiology. 1989 October; 3(4): 402-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2479928&dopt=Abstract

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Maternal vitamin A supplementation in relation to selected birth defects. Author(s): Werler MM, Lammer EJ, Rosenberg L, Mitchell AA. Source: Teratology. 1990 November; 42(5): 497-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2278025&dopt=Abstract

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Methods for a public health response to birth defects clusters. Author(s): Williams LJ, Honein MA, Rasmussen SA. Source: Teratology. 2002; 66 Suppl 1: S50-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239745&dopt=Abstract

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Molecular basis of environmentally induced birth defects. Author(s): Finnell RH, Waes JG, Eudy JD, Rosenquist TH. Source: Annual Review of Pharmacology and Toxicology. 2002; 42: 181-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807170&dopt=Abstract

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Multivitamin supplementation and risk of birth defects. Author(s): Werler MM, Hayes C, Louik C, Shapiro S, Mitchell AA. Source: American Journal of Epidemiology. 1999 October 1; 150(7): 675-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512421&dopt=Abstract

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Natural history of specific birth defects: Introduction. Author(s): Hall JG. Source: Birth Defects Orig Artic Ser. 1977; 13(3C): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=890104&dopt=Abstract

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Nebraska birth defects prevention program. Author(s): Beck RH. Source: Nebr Med J. 1974 May; 59(5): 166. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4832421&dopt=Abstract

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Negotiations, superstitions, and the plight of individuals born with severe birth defects. Author(s): Kenen RH. Source: Soc Sci Med [med Psychol Med Sociol]. 1980 June; 14A(4): 279-86. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6897934&dopt=Abstract

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Neurotomes and birth defects: a neuroanatomic method of interpretation of multiple congenital malformations. Author(s): North K, McCredie J. Source: Am J Med Genet Suppl. 1987; 3: 29-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3130864&dopt=Abstract

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New perspectives on folate status: a differential role for the vitamin in cardiovascular disease, birth defects and other conditions. Author(s): Lucock M, Daskalakis I. Source: British Journal of Biomedical Science. 2000; 57(3): 254-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050780&dopt=Abstract

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Newer procedures in the preconceptional, prenatal and early postnatal diagnosis of birth defects. Author(s): Nadler HL. Source: Birth Defects Orig Artic Ser. 1970 May; 6(1): 26-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5522716&dopt=Abstract

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No evidence of increase in birth defects and health problems among children born to Persian Gulf War Veterans in Mississippi. Author(s): Penman AD, Tarver RS, Currier MM. Source: Military Medicine. 1996 January; 161(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082741&dopt=Abstract

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Nonsyndromic cleft lip and palate is not associated with cancer or other birth defects. Author(s): Steinwachs EF, Amos C, Johnston D, Mulliken J, Stal S, Hecht JT. Source: American Journal of Medical Genetics. 2000 January 3; 90(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10602112&dopt=Abstract

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Normal or affected controls in case-control studies of congenital malformations and other birth defects: reporting bias issues. Author(s): Hook EB. Source: Epidemiology (Cambridge, Mass.). 1993 March; 4(2): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8452908&dopt=Abstract

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Nurses' role in preventing birth defects in offspring of women with phenylketonuria. Author(s): Acosta PB, Wright L. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 1992 July-August; 21(4): 270-6. Review. Erratum In: J Obstet Gynecol Neonatal Nurs 1992 September-October; 21(5): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1494969&dopt=Abstract

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O.R. exposure--cancer, miscarriages, and birth defects. Author(s): Corbett TH. Source: Women & Health. 1976 September-October; 1(5): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1028310&dopt=Abstract

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Objective methods for classification and the study of birth defects. Author(s): Estabrook GF. Source: Birth Defects Orig Artic Ser. 1977; 13(3A): 5-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=884242&dopt=Abstract

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Observations from the CDC: using health communications research to reduce birth defects. Author(s): Daniel KL. Source: Journal of Women's Health / the Official Publication of the Society for the Advancement of Women's Health Research. 1999 January-February; 8(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094075&dopt=Abstract

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Of monsters and prodigies: the interpretation of birth defects in the sixteenth century. Author(s): Walton MT, Fineman RM, Walton PJ. Source: American Journal of Medical Genetics. 1993 August 1; 47(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8368257&dopt=Abstract

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Office employment, work with video display terminals, and course of pregnancy. Reference mothers' experience from a Finnish case-referent study of birth defects. Author(s): Nurminen T, Kurppa K. Source: Scand J Work Environ Health. 1988 October; 14(5): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3201188&dopt=Abstract

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Offspring of male and female parents with thalidomide embryopathy: birth defects and functional anomalies. Author(s): Stromland K, Philipson E, Andersson Gronlund M. Source: Teratology. 2002 September; 66(3): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210472&dopt=Abstract

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OH: OB nurses arrange for transfer of pt.: did birth defects result from delay? Author(s): Tammelleo AD. Source: Regan Rep Nurs Law. 1997 November; 38(6): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9444230&dopt=Abstract

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On the ability of birth defects monitoring to detect new teratogens. Author(s): Khoury MJ, Holtzman NA. Source: American Journal of Epidemiology. 1987 July; 126(1): 136-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3109235&dopt=Abstract

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On the use of affected controls to address recall bias in case-control studies of birth defects. Author(s): Khoury MJ, James LM, Erickson JD. Source: Teratology. 1994 April; 49(4): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8073366&dopt=Abstract

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On the use of the term “syndrome” in clinical genetics and birth defects epidemiology. Author(s): Khoury MJ, Moore CA, Evans JA. Source: American Journal of Medical Genetics. 1994 January 1; 49(1): 26-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8172247&dopt=Abstract

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Oral contraceptives and birth defects. Author(s): Smithells RW. Source: Developmental Medicine and Child Neurology. 1981 June; 23(3): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7250546&dopt=Abstract

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Oral contraceptives and birth defects. Author(s): Janerich DT, Piper JM, Glebatis DM. Source: American Journal of Epidemiology. 1980 July; 112(1): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7395856&dopt=Abstract

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Oral contraceptives and birth defects. Author(s): Bross ID. Source: The New England Journal of Medicine. 1979 January 4; 300(1): 47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=758170&dopt=Abstract

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Oral contraceptives and birth defects. Author(s): Rothman KJ, Louik C. Source: The New England Journal of Medicine. 1978 September 7; 299(10): 522-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=683207&dopt=Abstract

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Oral contraceptives and estrogen combinations (excluding progestogens) during the first trimester--clearly increased the risk of overall birth defects. Author(s): Martinez-Frias ML, Rodriguez-Pinilla E, Bermejo E, Prieto L. Source: Teratology. 1998 August; 58(2): 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9787403&dopt=Abstract

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Organizations and institutions concerned with patients with genetic disorders or with birth defects in the Federal Republic of Germany. Author(s): Kuster W. Source: American Journal of Medical Genetics. 1985 March; 20(3): 547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3887914&dopt=Abstract

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Overall genetic significance of the use of epithelial cultures in studying human birth defects expressed in epithelium. Author(s): Murphy EA. Source: Birth Defects Orig Artic Ser. 1980; 16(2): 355-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7213977&dopt=Abstract

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Parental occupations and other risk factors associated with nonchromosomal single, chromosomal single, and multiple birth defects: a population-based study in Singapore from 1994 to 1998. Author(s): Chia SE, Shi LM, Chan OY, Chew SK, Foong BH. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 425-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592251&dopt=Abstract

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Paternal exposures and the question of birth defects. Author(s): Poynor DH, Lupkiewicz S, Sage SR, Carver VH, Kousseff BG, Lubs HA, Williams CA. Source: J Fla Med Assoc. 1997 June-July; 84(5): 323-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9260438&dopt=Abstract

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Patterns and trends of multiple congenital anomalies in birth defects surveillance systems. Author(s): Khoury MJ, Waters GD, Erickson JD. Source: Teratology. 1991 July; 44(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1957264&dopt=Abstract

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Pesticide appliers, biocides, and birth defects in rural Minnesota. Author(s): Garry VF, Schreinemachers D, Harkins ME, Griffith J. Source: Environmental Health Perspectives. 1996 April; 104(4): 394-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8732949&dopt=Abstract

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Pesticides and birth defects. Author(s): Czeizel AE. Source: Epidemiology (Cambridge, Mass.). 1996 January; 7(1): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664393&dopt=Abstract

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Population study of congenital hypothyroidism and associated birth defects, Atlanta, 1979-1992. Author(s): Roberts HE, Moore CA, Fernhoff PM, Brown AL, Khoury MJ. Source: American Journal of Medical Genetics. 1997 July 11; 71(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9215764&dopt=Abstract

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Potential risk of birth defects after acitretin discontinuation. Author(s): Maradit H, Geiger JM. Source: Dermatology (Basel, Switzerland). 1999; 198(1): 3-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200043&dopt=Abstract

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Predicting needs for special education resources for mental retardation from birth defects records. Author(s): Brewster MA, Kirby RS, Feild CR, Cunniff CM. Source: Public Health Reports (Washington, D.C. : 1974). 1992 May-June; 107(3): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1594739&dopt=Abstract

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Pregnancy outreach program in British Columbia: the prevention of alcohol-related birth defects. Author(s): Asante KO, Robinson GC. Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1990 January-February; 81(1): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2311056&dopt=Abstract

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Prepregnancy care and prevention of birth defects. Author(s): Eskes TK, Mooij PN, Steegers-Theunissen RP, Lips JP, Pasker-de Jong PC. Source: Journal of Perinatal Medicine. 1992; 20(4): 253-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1432549&dopt=Abstract

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Prevalence of birth defects among low-birth-weight infants. A population study. Author(s): Mili F, Edmonds LD, Khoury MJ, McClearn AB. Source: Am J Dis Child. 1991 November; 145(11): 1313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1951228&dopt=Abstract

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Prevalence of birth defects and parental work in Singapore live births from 1994 to 1998: a population-based study. Author(s): Shi LM, Chia SE, Chan OY, Chew SK, Foong BH. Source: Occupational Medicine (Oxford, England). 2002 September; 52(6): 325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361994&dopt=Abstract

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Prevalence of other birth defects among relatives of oral cleft probands. Author(s): Cereijo AI, Martinez-Frias ML. Source: Journal of Medical Genetics. 1992 July; 29(7): 516. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1640439&dopt=Abstract

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Preventing birth defects with folic acid. Author(s): Stein Q, Keppen L, Watson WJ. Source: S D J Med. 2002 September; 55(9): 389-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360641&dopt=Abstract

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Preventing birth defects: the challenges of diabetic fetotherapy and neural tube defects. Author(s): Carpenter MW. Source: Medicine and Health, Rhode Island. 1998 April; 81(4): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9597830&dopt=Abstract

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Prevention of birth defects: a task for a world alliance. Author(s): Wertelecki W, Katz M. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1996 May-June; 37(3): 168-72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8755169&dopt=Abstract

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Prevention of birth defects: folic acid. Author(s): Williamson R. Source: Biological Research for Nursing. 2001 July; 3(1): 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885912&dopt=Abstract

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Process of and problems in changing a birth defects registry reporting system. Author(s): Druschel C, Sharpe-Stimac M, Cross P. Source: Teratology. 2001; 64 Suppl 1: S30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745842&dopt=Abstract

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Public drinking water contamination and birthweight, prematurity, fetal deaths, and birth defects. Author(s): Bove FJ. Source: Toxicology and Industrial Health. 1996 March-April; 12(2): 255-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8794538&dopt=Abstract

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Public health impact of birth defects monitoring systems: national and international efforts. Author(s): Castilla EE, Peters PW. Source: Birth Defects Orig Artic Ser. 1992; 28(3): 27-36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1489954&dopt=Abstract

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Quantitative analysis of associations between birth defects and suspected human teratogens. Author(s): Khoury MJ, James LM, Lynberg MC. Source: American Journal of Medical Genetics. 1991 September 15; 40(4): 500-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1746618&dopt=Abstract

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Quinacrine sterilization: an assessment of risks for ectopic pregnancy, birth defects and cancer. Author(s): Kessel E. Source: Advances in Contraception : the Official Journal of the Society for the Advancement of Contraception. 1998 June; 14(2): 81-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9820926&dopt=Abstract

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Re: “Birth defects among offspring of firemen”. Author(s): Kallen B, Pradat P. Source: American Journal of Epidemiology. 1992 June 1; 135(11): 1318-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1626550&dopt=Abstract

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Re: “Completeness of the discharge diagnoses as a measure of birth defects recorded in the hospital birth record”. Author(s): Teratology. 1994 Mar;49(3):162-6 Source: American Journal of Epidemiology. 1992 August 15; 136(4): 498-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059421

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Re: “Office Employment, Work with Video Display Terminals, and Course of Pregnancy: Reference Mothers' Experience from a Finnish Case-Referent Study of Birth Defects” by T Nurminen, K Kurppa. Author(s): Marcus M. Source: Scand J Work Environ Health. 1989 April; 15(2): 156-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2772579&dopt=Abstract

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Registries of birth defects and genetic diseases. Author(s): Cordero JF. Source: Pediatric Clinics of North America. 1992 February; 39(1): 65-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1736257&dopt=Abstract

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Relation between trihalomethane compounds and birth defects. Author(s): Dodds L, King WD. Source: Occupational and Environmental Medicine. 2001 July; 58(7): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11404448&dopt=Abstract

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Relationship of vaginal spermicides to birth defects. Author(s): Manjuck JE. Source: J Fla Med Assoc. 1989 March; 76(3): 316-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2677215&dopt=Abstract

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Residence near power lines and the risk of birth defects. Author(s): Blaasaas KG, Tynes T, Lie RT. Source: Epidemiology (Cambridge, Mass.). 2003 January; 14(1): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500055&dopt=Abstract

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Residence, delivery and referral patterns of infants and fetuses with birth defects delivered in Hawaii, 1986-1999. Author(s): Forrester MB, Merz RD. Source: Public Health. 2003 March; 117(2): 128-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802980&dopt=Abstract

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Review of recent epidemiological studies on paternal occupations and birth defects. Author(s): Chia SE, Shi LM. Source: Occupational and Environmental Medicine. 2002 March; 59(3): 149-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886946&dopt=Abstract

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Risk factors for birth defects: data from the Atlanta Birth Defects Case-Control Study. Author(s): Erickson JD. Source: Teratology. 1991 January; 43(1): 41-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2006471&dopt=Abstract

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Risk of birth defects by parental occupational exposure to 50 Hz electromagnetic fields: a population based study. Author(s): Blaasaas KG, Tynes T, Irgens A, Lie RT. Source: Occupational and Environmental Medicine. 2002 February; 59(2): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850551&dopt=Abstract

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Risk of birth defects in a population exposed to environmental lead pollution. Author(s): Vinceti M, Rovesti S, Bergomi M, Calzolari E, Candela S, Campagna A, Milan M, Vivoli G. Source: The Science of the Total Environment. 2001 October 20; 278(1-3): 23-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669270&dopt=Abstract

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Risk of mental retardation among children born with birth defects. Author(s): Jelliffe-Pawlowski LL, Shaw GM, Nelson V, Harris JA. Source: Archives of Pediatrics & Adolescent Medicine. 2003 June; 157(6): 545-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796234&dopt=Abstract

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Risk of specific birth defects in relation to chlorination and the amount of natural organic matter in the water supply. Author(s): Hwang BF, Magnus P, Jaakkola JJ. Source: American Journal of Epidemiology. 2002 August 15; 156(4): 374-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181108&dopt=Abstract

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Role of structural birth defects in preterm delivery. Author(s): Shaw GM, Savitz DA, Nelson V, Thorp JM Jr. Source: Paediatric and Perinatal Epidemiology. 2001 April; 15(2): 106-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383574&dopt=Abstract

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Screening for birth defects: integrating laboratory evaluation, genetic counseling and clinical intervention. Author(s): Canick JA, Carr SR. Source: Medicine and Health, Rhode Island. 1998 April; 81(4): 122-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9597829&dopt=Abstract

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Selection bias and the use of controls with malformations in case-control studies of birth defects. Author(s): Lieff S, Olshan AF, Werler M, Savitz DA, Mitchell AA. Source: Epidemiology (Cambridge, Mass.). 1999 May; 10(3): 238-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10230831&dopt=Abstract

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Sex differences in the prevalence of human birth defects: a population-based study. Author(s): Lary JM, Paulozzi LJ. Source: Teratology. 2001 November; 64(5): 237-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745830&dopt=Abstract

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Some issues in the study of birth defects and recurrence risks in live births and “stillbirths”. Author(s): Hook EB. Source: American Journal of Human Genetics. 1990 October; 47(4): 741-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2220813&dopt=Abstract

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Sources of variability in birth defects prevalence rates. Author(s): Hobbs CA, Hopkins SE, Simmons CJ. Source: Teratology. 2001; 64 Suppl 1: S8-S13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745838&dopt=Abstract

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Spontaneous abortions and birth defects related to tap and bottled water use, San Jose, California, 1980-1985. Author(s): Wrensch M, Swan SH, Lipscomb J, Epstein DM, Neutra RR, Fenster L. Source: Epidemiology (Cambridge, Mass.). 1992 March; 3(2): 98-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1576232&dopt=Abstract

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State birth defects surveillance programs directory (updated July 1997). Author(s): Edmonds LD. Source: Teratology. 1997 July-August; 56(1-2): 63-114. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329166&dopt=Abstract

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State birth defects surveillance programs directory. Author(s): National Center on Birth Defects and Developmental Disabilities, CDC. Source: Teratology. 2002; 66 Suppl 1: S59-128. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239746&dopt=Abstract

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State-by-state cost of birth defects--1992. Author(s): Harris JA, James L. Source: Teratology. 1997 July-August; 56(1-2): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9329163&dopt=Abstract

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Survival and reproduction among males with birth defects and risk of recurrence in their children. Author(s): Lie RT, Wilcox AJ, Skjaerven R. Source: Jama : the Journal of the American Medical Association. 2001 February 14; 285(6): 755-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176913&dopt=Abstract

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Temporal trends in the prevalence of congenital malformations at birth based on the birth defects monitoring program, United States, 1979-1987. Author(s): Edmonds LD, James LM. Source: Mmwr. Cdc Surveillance Summaries : Morbidity and Mortality Weekly Report. Cdc Surveillance Summaries / Centers for Disease Control. 1990 December; 39(4): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2124329&dopt=Abstract

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Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry. Author(s): Bosi G, Garani G, Scorrano M, Calzolari E; IMER Working Party. Source: The Journal of Pediatrics. 2003 June; 142(6): 690-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838199&dopt=Abstract

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The Department of Defense Birth Defects Registry: overview of a new surveillance system. Author(s): Ryan MA, Pershyn-Kisor MA, Honner WK, Smith TC, Reed RJ, Gray GC. Source: Teratology. 2001; 64 Suppl 1: S26-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745841&dopt=Abstract

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The epidemiologic study of birth defects and pesticides. Author(s): Nurminen T. Source: Epidemiology (Cambridge, Mass.). 2001 March; 12(2): 145-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246573&dopt=Abstract

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The National Birth Defects Prevention Study. Author(s): Yoon PW, Rasmussen SA, Lynberg MC, Moore CA, Anderka M, Carmichael SL, Costa P, Druschel C, Hobbs CA, Romitti PA, Langlois PH, Edmonds LD. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 1: 32-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889273&dopt=Abstract

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The redemption of thalidomide: standardizing the risk of birth defects. Author(s): Timmermans S, Leiter V. Source: Social Studies of Science. 2000 February; 30(1): 41-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11624679&dopt=Abstract

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The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. Author(s): Hansen M, Kurinczuk JJ, Bower C, Webb S. Source: The New England Journal of Medicine. 2002 March 7; 346(10): 725-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882727&dopt=Abstract

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The risk of miscarriage and birth defects among women who use visual display terminals during pregnancy. Author(s): Goldhaber MK. Source: Reproductive Toxicology (Elmsford, N.Y.). 1990; 4(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2136022&dopt=Abstract

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The risk of miscarriage and birth defects among women who use visual display terminals during pregnancy. Author(s): Robinson H. Source: American Journal of Industrial Medicine. 1989; 15(3): 357-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2929622&dopt=Abstract

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The use of dysmorphology in birth defects epidemiology. Author(s): Friedman JM. Source: Teratology. 1992 February; 45(2): 187-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1615428&dopt=Abstract

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Understanding genetic and birth defects - an essential skill for the occupational health nurse. Author(s): Williams JK. Source: Occup Health Nurs. 1983 October; 31(10): 24-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6226888&dopt=Abstract

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US studies fail to find link between Gulf War and birth defects. Author(s): Veggeberg S. Source: Molecular Medicine Today. 1996 January; 2(1): 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8796845&dopt=Abstract

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Use of a job-exposure matrix to assess occupational exposures in relation to birth defects. Author(s): Louik C, Frumkin H, Ellenbecker MJ, Goldman RH, Werler MM, Mitchell AA. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2000 July; 42(7): 693-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914338&dopt=Abstract

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Use of birth defects monitoring programs for assessing the effects of maternal substance abuse on pregnancy outcomes. Author(s): Martin ML, Edmonds LD. Source: Nida Res Monogr. 1991; 114: 66-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1754024&dopt=Abstract

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Use of record linkage between a statewide genetics service and a Birth Defects/Congenital Malformations Register to determine use of genetic counselling services. Author(s): Halliday J, Griffin O, Bankier A, Rose C, Riley M. Source: American Journal of Medical Genetics. 1997 October 3; 72(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9295066&dopt=Abstract

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Use of stored newborn blood spots in research on birth defects: variation in retrieval rates by type of defect and infant characteristics. Author(s): Loffredo CA, Ewing CK. Source: American Journal of Medical Genetics. 1997 March 3; 69(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9066889&dopt=Abstract

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Use of the correlation of liability in twins and siblings in the study of birth defects. Author(s): Newman TB, Browner WS. Source: Teratology. 1988 October; 38(4): 303-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3238591&dopt=Abstract

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Using birth defects epidemiology to take CHARGE. Coloboma, Heart defect, choanal Atresia, Retardation, Genital, Ear anomaly. Author(s): Lin AE. Source: Teratology. 1999 December; 60(6): 332-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10590393&dopt=Abstract

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Using the Colorado birth defects monitoring program to connect families with services for children with special needs. Author(s): Montgomery A, Miller L. Source: Teratology. 2001; 64 Suppl 1: S42-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745844&dopt=Abstract

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Using the Hungarian Birth Defects Registry for surveillance, research and intervention. Author(s): Siffel C, Czeizel AE. Source: Cent Eur J Public Health. 1997 June; 5(2): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9208163&dopt=Abstract

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Vascular disruption birth defects and history of prenatal cocaine exposure: a case control study. Author(s): Hume RF Jr, Martin LS, Bottoms SF, Hassan SS, Banker-Collins K, Tomlinson M, Johnson MP, Evans MI. Source: Fetal Diagnosis and Therapy. 1997 September-October; 12(5): 292-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9430211&dopt=Abstract

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Vietnam veterans risk for fathering children with birth defects. Author(s): Sterling TD, Arundel A. Source: Jama : the Journal of the American Medical Association. 1985 August 2; 254(5): 609-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4009891&dopt=Abstract

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Visual clues to diagnosis of birth defects and genetic disease. Author(s): Wardinsky TD. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 1994 March-April; 8(2): 63-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8158490&dopt=Abstract

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Vitamin A and birth defects. Author(s): Mills JL, Simpson JL, Cunningham GC, Conley MR, Rhoads GG. Source: American Journal of Obstetrics and Gynecology. 1997 July; 177(1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9240579&dopt=Abstract

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Vitamin A and birth defects. Author(s): Khoury MJ, Moore CA, Mulinare J. Source: Lancet. 1996 February 3; 347(8997): 322. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8569374&dopt=Abstract

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Vitamin A and birth defects. Author(s): Lipson AH, Webster WS. Source: Lancet. 1996 February 3; 347(8997): 321-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8569373&dopt=Abstract

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Vitamin A and birth defects. Continuing caution is needed. Author(s): Oakley GP Jr, Erickson JD. Source: The New England Journal of Medicine. 1995 November 23; 333(21): 1414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7477124&dopt=Abstract

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Vitamin A, birth defects and multivitamin preparations. Author(s): Presbury D. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1997 January; 87(1): 73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9063320&dopt=Abstract

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Vitamin A, liver consumption, and risk of birth defects. Author(s): Nelson M. Source: Bmj (Clinical Research Ed.). 1990 November 24; 301(6762): 1176. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2261553&dopt=Abstract

•

Vitamins, fever and birth defects- consistent interaction or persistent bias? Author(s): Christensen K. Source: Epidemiology (Cambridge, Mass.). 2002 November; 13(6): 620-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410000&dopt=Abstract

•

Water chlorination and birth defects. Author(s): Magnus P, Jaakkola JJ, Skrondal A, Alexander J, Becher G, Krogh T, Dybing E. Source: Epidemiology (Cambridge, Mass.). 1999 September; 10(5): 513-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468423&dopt=Abstract

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Water chlorination and birth defects: a systematic review and meta-analysis. Author(s): Hwang BF, Jaakkola JJ. Source: Archives of Environmental Health. 2003 February; 58(2): 83-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899208&dopt=Abstract

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Water nitrates and CNS birth defects: a population-based case-control study. Author(s): Arbuckle TE, Sherman GJ, Corey PN, Walters D, Lo B. Source: Archives of Environmental Health. 1988 March-April; 43(2): 162-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3377550&dopt=Abstract

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Wealth and health in relation to birth defects mortality. Author(s): Cornel MC. Source: Journal of Epidemiology and Community Health. 2000 September; 54(9): 644. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942438&dopt=Abstract

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What is the relationship between birth defects and pregnancy bleeding? New perspectives provided by the NICHD workshop dealing with the association of chorionic villous sampling and the occurrence of limb reduction defects. Author(s): Brent RL. Source: Teratology. 1993 August; 48(2): 93-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8211823&dopt=Abstract

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CHAPTER 2. NUTRITION AND BIRTH DEFECTS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and birth defects.

Finding Nutrition Studies on Birth Defects 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 “birth defects” (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 “birth defects” (or a synonym): •

Folic acid for fighting birth defects? Source: Tufts-University-diet-and-nutrition-letter (USA). (November 1992). volume 10(9) page 1-2.

•

How folate can help prevent birth defects. Source: Kurtzweil, P. FDA-consumer (USA). (September 1996). volume 30(7) page 7-10.

Additional physician-oriented references include: •

Assessment of student pharmacists' knowledge concerning folic acid and prevention of birth defects demonstrates a need for further education. Author(s): Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA. [email protected] Source: Lynch, Sean M J-Nutr. 2002 March; 132(3): 439-42 0022-3166

•

Becoming proactive about birth defects. National Folic Acid Information Campaign begins. Source: Drake, P Morin, K H LaRose, K AWHONN-Lifelines. 1999 Aug-September; 3(4): 21-2 1091-5923

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Birth defects, Jimson weeds and bell curves. Author(s): Genetics Department, University of Wisconsin, Madison 53706, USA. Source: Crow, J F Genetics. 1997 September; 147(1): 1-6 0016-6731

•

Can vitamins prevent birth defects. Source: Liebman, B. Nutr-Action-Health-Lett. Washington, D.C. : Center for Science in the Public Interest. Jan/February 1990. volume 17 (1) page 8-9. ill., charts. 0199-5510

•

Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Author(s): Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. [email protected] Source: Hernan, Miguel A Hernandez Diaz, Sonia Werler, Martha M Mitchell, Allen A Am-J-Epidemiol. 2002 January 15; 155(2): 176-84 0002-9262

•

Folate fortification for the prevention of birth defects: case study. Author(s): Georgetown University Medical Center, Washington, DC, USA. [email protected] Source: Feinleib, M Beresford, S A Bowman, B A Mills, J L Rader, J I Selhub, J Yetley, E A Am-J-Epidemiol. 2001 Dec15; 154(12 Suppl): S60-9 0002-9262

•

Folic acid and prevention of birth defects. Author(s): Division of Developmental Disabilities, The Children's Hospital of Iowa, Iowa City, USA. [email protected] Source: Van Dyke, Don C Stumbo, Phyllis J Mary, J Berg Niebyl, Jennifer R Dev-MedChild-Neurol. 2002 June; 44(6): 426-9 0012-1622

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Folic acid in the prevention of birth defects. Author(s): Greenwood Genetics Center, SC 29646, USA. Source: Allen, W P Curr-Opin-Pediatr. 1996 December; 8(6): 630-4 1040-8703

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Folic acid supplementation and prevention of birth defects. Author(s): March of Dimes, White Plains, NY 10605, USA. [email protected] Source: Green, Nancy S J-Nutr. 2002 August; 132(8 Suppl): 2356S-2360S 0022-3166

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Good news for women and babies: folic acid prevents birth defects. Author(s): Capitol Associates, Inc, Washington, DC, USA. Source: Havens, D H Levin, B R J-Pediatr-Health-Care. 1999 Sep-October; 13(5): 255-8 0891-5245

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Impact of an educational seminar on high school students' knowledge of folic acid supplementation and its role in the prevention of birth defects. Author(s): St Joseph Hospital in Bellingham, Washington, USA. Source: Johnson, Patricia A Stadler, Diane D Feldkamp, Marcia Webber, Beverly J-AmDiet-Assoc. 2002 Mar; 102(3 Suppl): S78-81 0002-8223

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March of Dimes enlists professionals in fight against birth defects. Source: Anonymous Neonatal-Netw. 2000 April; 19(3): 64 0730-0832

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Maternal diabetes and its cell membrane abnormalities as they affect the foetus: implications for the mother and birth defects. Author(s): Department of Endocrinology, St Thomas's Hospital, UK. Source: Lowy, C Nutr-Health. 2001; 15(3-4): 245-50 0260-1060

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Maternal fever, multivitamin use, and selected birth defects: evidence of interaction? Author(s): National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Highway NE, Atlanta, GA 30341, USA. [email protected] Source: Botto, Lorenzo D Erickson, J David Mulinare, Joseph Lynberg, Michele C Liu, Yecai Epidemiology. 2002 July; 13(4): 485-8 1044-3983

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Molecular basis of environmentally induced birth defects. Author(s): Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, USA. [email protected] Source: Finnell, Richard H Waes, Janee Gelineau van Eudy, James D Rosenquist, Thomas H Annu-Rev-Pharmacol-Toxicol. 2002; 42: 181-208 0362-1642

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Nurses' role in preventing birth defects in offspring of women with phenylketonuria. Author(s): Ross Laboratories, Columbus, Ohio. Source: Acosta, P B Wright, L J-Obstet-Gynecol-Neonatal-Nurs. 1992 Jul-August; 21(4): 270-6 0884-2175

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Possible basis for primary prevention of birth defects with folic acid. Author(s): Department of Obstetrics and Gynaecology, University Hospital, Nijmegen, The Netherlands. Source: Eskes, T K Fetal-Diagn-Ther. 1994 May-June; 9(3): 149-54 1015-3837

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Preventing birth defects with folic acid. Source: Stein, Q Keppen, L Watson, W J S-D-J-Med. 2002 September; 55(9): 389-91 00383317

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Prevention of birth defects: folic acid. Author(s): Department of Obstetrics and Gynecology, College of Medicine, University of Iowa, Iowa City 52242-1080, USA. [email protected] Source: Williamson, R Biol-Res-Nurs. 2001 July; 3(1): 33-8 1099-8004

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Risks for birth defects or low birth weight: air pollution.medications.and caffeine. Source: Anonymous Child-Health-Alert. 2002 February; 20: 2 1064-4849

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The prevention of diabetes-associated birth defects. Author(s): Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.

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Source: Reece, E A Gabrielli, S Abdalla, M Semin-Perinatol. 1988 October; 12(4): 292-301 0146-0005 •

Vitamins, fever and birth defects- consistent interaction or persistent bias? Author(s): Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense. [email protected] Source: Christensen, K Epidemiology. 2002 November; 13(6): 620-1 1044-3983

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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

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

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

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

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

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

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

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic 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 A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com

•

Minerals Biotin Source: Healthnotes, Inc.; www.healthnotes.com Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Potassium-Sparing Diuretics Source: Integrative Medicine Communications; www.drkoop.com

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Quercetin Source: Healthnotes, Inc.; www.healthnotes.com Retinol Source: Integrative Medicine Communications; www.drkoop.com Vanadium Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com •

Food and Diet Lentils Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,99,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND BIRTH DEFECTS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to birth defects. At the conclusion of this chapter, we will provide additional sources.

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

“Such monstrous births”: a neglected aspect of the Antinomian controversy. Author(s): Schutte AJ. Source: Renaiss Q. 1985 Spring; 38(1): 85-106. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11611708&dopt=Abstract

•

Assessment of student pharmacists' knowledge concerning folic acid and prevention of birth defects demonstrates a need for further education. Author(s): Lynch SM. Source: The Journal of Nutrition. 2002 March; 132(3): 439-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880568&dopt=Abstract

•

Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Author(s): Correa A, Botto L, Liu Y, Mulinare J, Erickson JD.

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Source: Pediatrics. 2003 May; 111(5 Part 2): 1146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728128&dopt=Abstract •

Elevated birth defects in racial or ethnic minority children of women living near hazardous waste sites. Author(s): Orr M, Bove F, Kaye W, Stone M. Source: International Journal of Hygiene and Environmental Health. 2002 March; 205(12): 19-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018013&dopt=Abstract

•

Folate fortification for the prevention of birth defects: case study. Author(s): Feinleib M, Beresford SA, Bowman BA, Mills JL, Rader JI, Selhub J, Yetley EA. Source: American Journal of Epidemiology. 2001 December 15; 154(12 Suppl): S60-9. Review. Erratum In: Am J Epidemiol 2002 January 15; 155(2): 189. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744531&dopt=Abstract

•

Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. Author(s): Refsum H. Source: The British Journal of Nutrition. 2001 May; 85 Suppl 2: S109-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509098&dopt=Abstract

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Folic acid and prevention of birth defects. Author(s): Van Dyke DC, Stumbo PJ, Mary JB, Niebyl JR. Source: Developmental Medicine and Child Neurology. 2002 June; 44(6): 426-9. Review. Erratum In: Dev Med Child Neurol. 2003 May; 45(5): 360. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088312&dopt=Abstract

•

Folic acid antagonists during pregnancy and the risk of birth defects. Author(s): Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Source: The New England Journal of Medicine. 2000 November 30; 343(22): 1608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096168&dopt=Abstract

•

Folic acid supplementation and prevention of birth defects. Author(s): Green NS. Source: The Journal of Nutrition. 2002 August; 132(8 Suppl): 2356S-2360S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163692&dopt=Abstract

•

Impact of an educational seminar on high school students' knowledge of folic acid supplementation and its role in the prevention of birth defects. Author(s): Johnson PA, Stadler DD, Feldkamp M, Webber B.

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Source: Journal of the American Dietetic Association. 2002 March; 102(3 Suppl): S78-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902395&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

General Overview AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Birth Defects Source: Integrative Medicine Communications; www.drkoop.com Birth Defects Prevention Source: Healthnotes, Inc.; www.healthnotes.com

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Depression Source: Integrative Medicine Communications; www.drkoop.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Alternative names: Painful Menstruation Source: Prima Communications, Inc.www.personalhealthzone.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Pregnancy and Postpartum Support Source: Healthnotes, Inc.; www.healthnotes.com Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Pyloric Stenosis Source: Integrative Medicine Communications; www.drkoop.com Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com Rubella Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements 5-aminosalicylic Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Ananas Comosus Source: Integrative Medicine Communications; www.drkoop.com

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Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Biguanides Source: Integrative Medicine Communications; www.drkoop.com Bile Acid Sequestrants Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Bromelain Alternative names: Ananas comosus, Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Echinacea Alternative names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea Pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea Purpurea Source: Integrative Medicine Communications; www.drkoop.com Electrolytes Source: Integrative Medicine Communications; www.drkoop.com

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Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Macrolides Source: Integrative Medicine Communications; www.drkoop.com Miscellaneous Source: Integrative Medicine Communications; www.drkoop.com Miscellaneous Preparations Source: Integrative Medicine Communications; www.drkoop.com Nonsteroidal Anti-inflammatory Drugs (nsaids) Source: Integrative Medicine Communications; www.drkoop.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Proton Pump Inhibitors (gastric Acid Secretion Inhibitors) Source: Integrative Medicine Communications; www.drkoop.com Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com Salicylates Source: Integrative Medicine Communications; www.drkoop.com Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Triamterene Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim Source: Healthnotes, Inc.; www.healthnotes.com Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.com Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com

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

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CHAPTER 4. DISSERTATIONS ON BIRTH DEFECTS Overview In this chapter, we will give you a bibliography on recent dissertations relating to birth defects. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “birth defects” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on birth defects, we have not necessarily excluded nonmedical dissertations in this bibliography.

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

Alcohol-Related Birth Defects (ARBD): Perspectives of Early-childhood Educators in South Dakota (fetal Alcohol Syndrome) by Boettcher, Lynn Marie, Edd from University of South Dakota, 1995, 156 pages http://wwwlib.umi.com/dissertations/fullcit/9542564

•

An Infant with a Birth Defect: a Birth Crisis Intervention Model for Medical Personnel by Price, Mary Ann, Edd from Columbia University Teachers College, 1981, 180 pages http://wwwlib.umi.com/dissertations/fullcit/8207336

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Process and Impact Evaluation of Selected March of Dimes Birth Defects Foundation Health Communications: a Case for the Role of Formative Evaluation by Foley, Mary Elizabeth, Edd from Columbia University Teachers College, 1987, 188 pages http://wwwlib.umi.com/dissertations/fullcit/8710128

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•

The Application of Sensation-seeking Theory to a Public Communications Campaign in Kentucky: the Prevention of Birth Defects due to Substance Use by Prather, James Mark, Phd from University of Kentucky, 1994, 190 pages http://wwwlib.umi.com/dissertations/fullcit/9519766

•

Water Chlorination and Birth Defects by Hwang, Bing-fang; Phd from The Johns Hopkins University, 2003, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3068171

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

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CHAPTER 5. CLINICAL TRIALS AND BIRTH DEFECTS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning birth defects.

Recent Trials on Birth Defects The following is a list of recent trials dedicated to birth defects.8 Further information on a trial is available at the Web site indicated. •

Pesticides--Health Fertility and Reproductive Risk Condition(s): Birth Defects; Miscarriages; Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This project is designed to establish whether pesticides or other environmental agents have a role in the excess birth defects identified in the Red River Valley of Minnesota. In this human study, laboratory based health parameters will be used to key in health survey data. In vitro data will be developed to mechanistic information. Concordant results among these study features will provide a weight of evidence approach. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015561

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. 8

These are listed at www.ClinicalTrials.gov.

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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 “birth defects” (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/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

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

•

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

•

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/

•

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

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. BOOKS ON BIRTH DEFECTS Overview This chapter provides bibliographic book references relating to birth defects. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on birth defects 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 “birth defects” (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 birth defects: •

Look out: A nine session program to encourage African American young men to help prevent alcohol related birth defects Source: Madison, WI: Wisconsin Clearinghouse for Prevention Resources. 1996. 74 pp. Contact: Available from Wisconsin Clearinghouse For Prevention Resources, P.O. Box 1468, Madison, WI 53701-1468. Telephone: (608) 263-2797 or (800) 322-1468 / fax: (608) 262-6346 / e-mail: [email protected] / Web site: http://www.uhs.wisc.edu/wch/. $24.95 plus $3.00 shipping and handling.

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Summary: The purpose of this nine-session curriculum for young African American men is to stimulate and nurture the desire to adopt the values necessary to be concerned about fetal alcohol syndrome and fetal alcohol effects and their impact on their partners, families, communities, and themselves. The sessions are designed to help group members identify, and sometimes change, their attitudes and beliefs, increase their knowledge and understanding, and either change their behavior, or affirm it if they are already making good decisions. Tips for the discussion leader, suggestions, guidelines for interactive activities, and objectives for each lesson help the instructor to plan sessions. Learning strategies are discussed. An extensive list of national resources is provided, along with current factual information on African American youth, alcohol use during pregnancy, and alcohol-related congenital disabilities. •

Maternal risk assessment for fetal alcohol syndrome and alcohol related birth defects and neurodevelopmental disorders Source: Grand Forks, ND: North Dakota Fetal Alcohol Syndrome Center. (between 1997 and 2002?). 29 pp. Contact: Available from North Dakota Fetal Alcohol Syndrome Center, 501 North Columbia Road, Grand Forks, ND 58203. Telephone: (701) 777-3683 / Web site: http://www.online-clinic.com. Contact for cost information. Summary: This report describes a method for assessing pregnant women at increased risk of having a baby with fetal alcohol syndrome (FAS). Topics include risk and exposure assessments; risk stratification; clinical implications and services; and prevention strategies. The report also contains score sheets and questionnaires for the clinician to use in assessing risk before and during pregnancy. Charts and graphs illustrate the model and other statistical data relating to FAS. Also provided are pocket guides to aid in screening for alcohol abuse and potential fetal exposure.

•

Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner Source: Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. 130 p. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number BMA0097. Summary: This volume provides a compendium of the American Academy of Pediatrics (AAP) guidelines and resources for health care providers who are working with patients who have genetic disorders and birth defects. The compendium serves as a diagnostic and management resource guide for pediatricians and primary care physicians. Although some of the disorders covered are relatively uncommon, it is likely that most pediatricians will encounter and care for a few such patients in their practice panel. The authors emphasize that early intervention services, multidisciplinary care, and developmental assessment and management form a major part of continuing care for many children with genetic conditions. The AAP Policy Statements are provided on folic acid for the prevention of neural tube defects, issues in newborn screening, maternal phenylketonuria, maternal serum alpha-fetoprotein screening, newborn screening for congenital hypothyroidism, newborn screening fact sheets, and prenatal genetic diagnosis for pediatricians. In addition, policy statements are provided for the health supervision of children born with the following conditions: achondroplasia, Down

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syndrome, fragile X syndrome, Marfan syndrome, neurofibromatosis, sickle cell disease, and Turner syndrome. Each Policy Statement includes references. The compendium includes extensive appendices, covering topics including fetal alcohol syndrome, general principles of care for children and adolescents with genetic and other chronic health conditions, hospital stays, medical homes, preventive pediatric health care, and transition of care provided for adolescents with special health care needs. The compendium also lists the references where the policy statements were first published, the contact information for national and regional genetic organizations, and the members of the AAP Section on Genetics and Birth Defects.

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 “birth defects” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “birth defects” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “birth defects” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

21st Century Complete Guide to DOD Deployment Health Support Directorate, Project SHAD (Shipboard Hazard and Defense) Warship Chemical and Biological Warfare Tests, Depleted Uranium, Birth Defects (CD-ROM) by Department of Defense (2003); ISBN: 159248283X; http://www.amazon.com/exec/obidos/ASIN/159248283X/icongroupinterna

•

A Guide to Human Chromosome Defects (March of Dimes Birth Defects Foundation Series, Vol 16 No 6) by Natalie W. Paul (Editor) (1980); ISBN: 0686308212; http://www.amazon.com/exec/obidos/ASIN/0686308212/icongroupinterna

•

Abnormal Embryogenesis: Cellular and Molecular Aspects (Advances in the Study of Birth Defects; V. 3) by T. V. N. Persaud; ISBN: 0839114702; http://www.amazon.com/exec/obidos/ASIN/0839114702/icongroupinterna

•

Abnormal Embryogenesis: Molecular and Cellular Aspects (Advances in the Study of Birth Defects) by T.V.N. Persaud (Editor); ISBN: 0852002807; http://www.amazon.com/exec/obidos/ASIN/0852002807/icongroupinterna

•

Abstracts of papers; 4th International Conference on Birth Defects, Vienna, Austria, 28 September, 1973; ISBN: 902191199X; http://www.amazon.com/exec/obidos/ASIN/902191199X/icongroupinterna

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Adolescent Pregnancy: Nursing Perspectives on Prevention (Birth Defects Original Article Series, Vol 27, No 1) by S. S. Humenick (1991); ISBN: 9992841745; http://www.amazon.com/exec/obidos/ASIN/9992841745/icongroupinterna

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Alcohol and Birth Defects: The Fetal Alcohol Syndrome and Related Disorders by Peter L. Petrakis; ISBN: 9999539599; http://www.amazon.com/exec/obidos/ASIN/9999539599/icongroupinterna

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Alcohol Consumption, Cancer and Birth Defects; ISBN: 084937295X; http://www.amazon.com/exec/obidos/ASIN/084937295X/icongroupinterna

126 Birth Defects

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Alpha-Fetoprotein and Congenital Disorders (Birth Defects Institute Symposia) by New York State Health Department Birth Defects Symposium 1983 Albany, et al; ISBN: 0125016301; http://www.amazon.com/exec/obidos/ASIN/0125016301/icongroupinterna

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Annual Review of Birth Defects, 1982 by Sara C. Finley (Editor), et al; ISBN: 0471835048; http://www.amazon.com/exec/obidos/ASIN/0471835048/icongroupinterna

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Anorectal Malformations in Children: Update 1988 (Birth Defects, Original Article Series, Vol 24, No 4) by F. Douglas Stephens, et al; ISBN: 0471500399; http://www.amazon.com/exec/obidos/ASIN/0471500399/icongroupinterna

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Anthropometric Measurements of the Newborn Infant (Birth Defects Original Article Series, Vol 20, No 7) by Natalie W. Paul (Editor); ISBN: 9996567419; http://www.amazon.com/exec/obidos/ASIN/9996567419/icongroupinterna

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Before We Are Born: Essentials of Embryology and Birth Defects by Keith L., Ph.D. Moore, T. V. N., Md. Persaud; ISBN: 072169408X; http://www.amazon.com/exec/obidos/ASIN/072169408X/icongroupinterna

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Before we are born; basic embryology and birth defects by Keith L. Moore; ISBN: 0721664504; http://www.amazon.com/exec/obidos/ASIN/0721664504/icongroupinterna

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Bendectin and Birth Defects: The Challenges of Mass Toxic Substances Litigation by Michael D. Green; ISBN: 0812232577; http://www.amazon.com/exec/obidos/ASIN/0812232577/icongroupinterna

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BERGSMA CLINICAL DELINEATION OF BIRTH DEFECTS - LIMB MALFORMATIONS by D BERGSMA; ISBN: 0471563412; http://www.amazon.com/exec/obidos/ASIN/0471563412/icongroupinterna

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BERGSMA NATURAL HISTORY OF SPECIFIC BIRTH DEFECTS by D BERGSMA; ISBN: 0471562971; http://www.amazon.com/exec/obidos/ASIN/0471562971/icongroupinterna

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BERGSMA NUMERICAL TAXONOMY OF BIRTH DEFECTS AND POLYGENIC DISORDERS by D BERGSMA; ISBN: 0471563013; http://www.amazon.com/exec/obidos/ASIN/0471563013/icongroupinterna

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Birth Defects & Speech-Language Disorders by Shirley N. Sparks (1984); ISBN: 0316804932; http://www.amazon.com/exec/obidos/ASIN/0316804932/icongroupinterna

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Birth Defects (Diseases and People) by Lisa Iannucci, Lisa Lannucci (2000); ISBN: 0766011860; http://www.amazon.com/exec/obidos/ASIN/0766011860/icongroupinterna

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Birth Defects (Encyclopedia of Health) by Edward Edelson; ISBN: 0791000583; http://www.amazon.com/exec/obidos/ASIN/0791000583/icongroupinterna

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Birth defects : proceedings of the fourth International Conference, Vienna, Austria, 28 September, 1973; ISBN: 9021902117; http://www.amazon.com/exec/obidos/ASIN/9021902117/icongroupinterna

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Birth Defects and Drugs in Pregnancy by Olli P. Heinonen; ISBN: 0884160343; http://www.amazon.com/exec/obidos/ASIN/0884160343/icongroupinterna

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Birth defects and fetal development; endocrine and metabolic factors; [proceedings]; ISBN: 0398027846; http://www.amazon.com/exec/obidos/ASIN/0398027846/icongroupinterna

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Birth Defects and Infant Mortality: A National and Regional Profile 1996: Statbook Technical Report Series by Joann Petrini (Editor), March of Dimes Birth Defects Foundation; ISBN: 0865250723; http://www.amazon.com/exec/obidos/ASIN/0865250723/icongroupinterna

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Birth Defects and Speech Language Disorders by Shirley N. Sparks; ISBN: 0933014066; http://www.amazon.com/exec/obidos/ASIN/0933014066/icongroupinterna

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Birth Defects Compendium (1983); ISBN: 0845102036; http://www.amazon.com/exec/obidos/ASIN/0845102036/icongroupinterna

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Birth Defects Compendium by Daniel Bergsma (Editor); ISBN: 0471832987; http://www.amazon.com/exec/obidos/ASIN/0471832987/icongroupinterna

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Birth Defects Encyclopedia; ISBN: 0865420882; http://www.amazon.com/exec/obidos/ASIN/0865420882/icongroupinterna

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Birth Defects Encyclopedia: The Comprehensive, Systematic, Illustrated Reference Source for the Diagnosis, Delineation, Etiology, Biodynamics, Occur by Mary Buyse (Editor) (1992); ISBN: 0865422281; http://www.amazon.com/exec/obidos/ASIN/0865422281/icongroupinterna

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Birth defects in Papua New Guinea by Richard Dryden; ISBN: 9980840331; http://www.amazon.com/exec/obidos/ASIN/9980840331/icongroupinterna

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Birth Defects International Directory of Genetic Service by Henry T. Lynch (1990); ISBN: 999434305X; http://www.amazon.com/exec/obidos/ASIN/999434305X/icongroupinterna

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Birth Defects, Risks and Consequences: Proceedings of a Symposium on Birth Defects, Risks and Consequences, Sponsored by the Birth Defects Institute by Kelly and; ISBN: 0124034500; http://www.amazon.com/exec/obidos/ASIN/0124034500/icongroupinterna

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Birth defects: atlas and compendium by Daniel Bergsma; ISBN: 0683063669; http://www.amazon.com/exec/obidos/ASIN/0683063669/icongroupinterna

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Birth Defects: Clinical and Ethical Considerations by Sara C. Finley (1983); ISBN: 084511056X; http://www.amazon.com/exec/obidos/ASIN/084511056X/icongroupinterna

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Birth Defects: Cumulative Index: Vols. I-XVI, 1965-1980, Vol. 18 by Natalie W. Paul (Editor) (1982); ISBN: 0845110497; http://www.amazon.com/exec/obidos/ASIN/0845110497/icongroupinterna

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Bone Marrow Transplantation for Treatment of Lysosomal Storage Diseases (Birth Defects: Original Articles Series Vol 22, No 1, 1986) by William Krivit (Editor), Natalie W. Paul (Editor); ISBN: 0471851604; http://www.amazon.com/exec/obidos/ASIN/0471851604/icongroupinterna

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Case-control study of congenital anomalies and Vietnam service (birth defects study) : report to the Minister for Veterans' Affairs; ISBN: 0644012366; http://www.amazon.com/exec/obidos/ASIN/0644012366/icongroupinterna

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Central Nervous System and Craniofacial Malformations. Ed by T.V.N. Persaud (Advances in the Study of Birth Defects, Vol 7) by Persaud; ISBN: 0852003986; http://www.amazon.com/exec/obidos/ASIN/0852003986/icongroupinterna

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Central Nervous System and Cranofacial Malformations (Advances in the Study of Birth Defects, Vol 7) by T.V. Peraud; ISBN: 0471565911; http://www.amazon.com/exec/obidos/ASIN/0471565911/icongroupinterna

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Chemically Induced Birth Defects (1993); ISBN: 0824772474; http://www.amazon.com/exec/obidos/ASIN/0824772474/icongroupinterna

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Chemically Induced Birth Defects by James L. Schardein; ISBN: 0824787757; http://www.amazon.com/exec/obidos/ASIN/0824787757/icongroupinterna

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Combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect : proceedings of a symposium and workshop on combined immunodeficiency disease and adenosine deaminase deficiency, a molecular defect, sponsored by the Birth Defects Institute of the New York State Department of Health, held in Albany, New York, October 2-3, 1973; ISBN: 0124927505; http://www.amazon.com/exec/obidos/ASIN/0124927505/icongroupinterna

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Congenital Malformations Worldwide: A Report from the International Clearinghouse for Birth Defects Monitoring Systems: A Non-Governmental Organiza by Peters, International Clearinghouse for Birth De; ISBN: 0444891374; http://www.amazon.com/exec/obidos/ASIN/0444891374/icongroupinterna

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Cranial Facial Structures and Connective Tissue Disorders (Birth Defects Original Article Series Vol 25, No 4); ISBN: 9991647953; http://www.amazon.com/exec/obidos/ASIN/9991647953/icongroupinterna

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Craniofacial Mesenchyme in Morphogenesis and Malformation (Birth Defects Original Article Series, Vol 20, No 3) by Kenneth S. Brown (Editor), et al; ISBN: 0471833401; http://www.amazon.com/exec/obidos/ASIN/0471833401/icongroupinterna

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DANES IN VITRO EPITHELIA AND BIRTH DEFECTS by BS DANES; ISBN: 0471563854; http://www.amazon.com/exec/obidos/ASIN/0471563854/icongroupinterna

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Dermatoglyphics: Science in Transition (Birth Defects, Original Article Series, Vol 27, No 2) by Chris C. Plato (Editor), et al; ISBN: 0471561045; http://www.amazon.com/exec/obidos/ASIN/0471561045/icongroupinterna

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Detection of Cancer Predisposition: Laboratory Approaches: Monograph, No. 3 (Birth Defects: Original Article Series, Vol 26, No. 1, 1990) by Lawrence Spatz, et al (1990); ISBN: 9991648003; http://www.amazon.com/exec/obidos/ASIN/9991648003/icongroupinterna

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Diagnostic Accuracy: Effect on Treatment Planning (Birth Defects: Original Articles Series, Vol 21, No 2) by Robert J. Shprintzen, Natilie W. Paul (Editor); ISBN: 047184392X; http://www.amazon.com/exec/obidos/ASIN/047184392X/icongroupinterna

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Dietary Factors and Birth Defects by Raghubir P. Sharma (Editor) (1993); ISBN: 0934394083; http://www.amazon.com/exec/obidos/ASIN/0934394083/icongroupinterna

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Disorders of connective tissue : the 1974 Birth Defects Conference held at Newport Beach, California; ISBN: 0883720337; http://www.amazon.com/exec/obidos/ASIN/0883720337/icongroupinterna

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Disorders of the Developing Nervous System: Changing Views on Their Origins, Diagnoses, and Treatments (Albany Birth Defects Symposium) by John W. Swann (Editor), Anne Messer (Editor); ISBN: 0471502685; http://www.amazon.com/exec/obidos/ASIN/0471502685/icongroupinterna

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Drug Toxicity in Embryonic Dev I: Adv Understanding Mechanisms of Birth Defects: Morphogenesis Etc. by R. J. Akhurst (Editor), et al; ISBN: 3540612599; http://www.amazon.com/exec/obidos/ASIN/3540612599/icongroupinterna

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Drugs and Birth Defects (Drug Abuse Prevention Library) by Nancy Shniderman, Sue Hurwitz; ISBN: 0823926214; http://www.amazon.com/exec/obidos/ASIN/0823926214/icongroupinterna

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Effective Prevention of Preterm Birth: The French Experience at Haguenau (Birth Defects Original Article Series Vol 25 No 1); ISBN: 9991647414; http://www.amazon.com/exec/obidos/ASIN/9991647414/icongroupinterna

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Embryos, Genes and Birth Defects by Peter Thorogood (Editor); ISBN: 0471971960; http://www.amazon.com/exec/obidos/ASIN/0471971960/icongroupinterna

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Encyclopedia of Genetic Disorders & Birth Defects by James Wynbrandt, Mark D. Ludman; ISBN: 0816038090; http://www.amazon.com/exec/obidos/ASIN/0816038090/icongroupinterna

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Environment and Birth Defects (Environmental Science Series) by James G. Wilson; ISBN: 0127577505; http://www.amazon.com/exec/obidos/ASIN/0127577505/icongroupinterna

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Environmental Causes of Human Birth Defects by T.V.N. Persaud, et al; ISBN: 0398056668; http://www.amazon.com/exec/obidos/ASIN/0398056668/icongroupinterna

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Environmental chemicals causing cancer and genetic birth defects : developing a strategy to minimize human exposure by Bruce N. Ames; ISBN: 0877722617; http://www.amazon.com/exec/obidos/ASIN/0877722617/icongroupinterna

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Families against society : a study of reactions to children with birth defects by Rosalyn Benjamin Darling; ISBN: 0803912862; http://www.amazon.com/exec/obidos/ASIN/0803912862/icongroupinterna

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Fetal Pathology Laboratory Manual (Birth Defects Original Article Series, Vol 19, No 2) by Julianne M. Byrne, Natalie W. Paul (Editor) (1982); ISBN: 9996567303; http://www.amazon.com/exec/obidos/ASIN/9996567303/icongroupinterna

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Folic Acid: The Essential B Vitamin That Prevents Birth Defects and Promotes Optimal Health by Allan, M.D. Spreen, Allan N. Spreen (2000); ISBN: 1580540848; http://www.amazon.com/exec/obidos/ASIN/1580540848/icongroupinterna

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Fragile X Cancer Cytogenetics: Proceedings of the 1989 Albany Birth Defects Symposium XX (Progress in Clinical and Biological Research, Vol 368) by Ann M. Willey (Editor), Patricia D. Murphy (Editor); ISBN: 0471560987; http://www.amazon.com/exec/obidos/ASIN/0471560987/icongroupinterna

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Gene Regulation and Fetal Development: Proceedings of the Third International Workshop on Fetal Genetic Pathology, Held in Perugia, Italy, June 3-6, 1993 (Birth Defects Original Article Series, Vol 30, No 1) by Italy International Workshop on Fetal

130 Birth Defects

Genetic Pathology 1993 Perugia, et al; ISBN: 047113791X; http://www.amazon.com/exec/obidos/ASIN/047113791X/icongroupinterna •

Genetic Aspects of Developmental Pathology (Birth Defects Original Article Series, Vol 23, No 1) by Enid F. Gilbert (Editor), John M. Opitz (Editor); ISBN: 0471630012; http://www.amazon.com/exec/obidos/ASIN/0471630012/icongroupinterna

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Genetic aspects of developmental pathology : solicited papers and proceedings of a symposium held September 26-28, 1985 in Madison, Wisconsin, as part of the interim meeting of the Society for Pediatric Pathology and sponsored by the University of Wisconsin--Madison and the March of Dimes Birth Defects Foundation; ISBN: 0845110632; http://www.amazon.com/exec/obidos/ASIN/0845110632/icongroupinterna

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Genetic Counseling Principles in Action: A Casebook (Birth Defects Original Article Series, Vol 25, No 5) by Joan H. Marks, et al; ISBN: 9991647163; http://www.amazon.com/exec/obidos/ASIN/9991647163/icongroupinterna

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Genetic disease : screening and management: proceedings of the 1985 Albany Birth Defects Symposium, held in Albany, New York, September 30-October 1, 1985; ISBN: 0845142240; http://www.amazon.com/exec/obidos/ASIN/0845142240/icongroupinterna

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Genetic Disease: Screening and Management: Proceedings of the 1985 Albany Birth Defects Symposium, Held in Albany, New York, Sept 30-Oct 1, 1985 by Thomas P. Carter (Editor), Ann M. Willey (Editor); ISBN: 0471625043; http://www.amazon.com/exec/obidos/ASIN/0471625043/icongroupinterna

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Genetic Disorders and Birth Defects in Families and Society (Birth Defects Original Article Series, Vol 20, No 4) by Natalie W. Paul (Editor); ISBN: 9996567370; http://www.amazon.com/exec/obidos/ASIN/9996567370/icongroupinterna

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Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner by American Academy of Pediatrics, Aap; ISBN: 0910761809; http://www.amazon.com/exec/obidos/ASIN/0910761809/icongroupinterna

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Genetic Disorders and Prenatal Diagnosis. Ed by T.V.N. Persaud (Advances in the Study of Birth Defects, Vol 5) by Persaud; ISBN: 085200396X; http://www.amazon.com/exec/obidos/ASIN/085200396X/icongroupinterna

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Genetic Disorders, Syndromology and Prenatal Diagnosis (Advances in the Study of Birth Defects: Vol 5) by T.V. Persaud; ISBN: 047156592X; http://www.amazon.com/exec/obidos/ASIN/047156592X/icongroupinterna

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Genetic Risk, Risk Perception, and Decision Making (Birth Defects, Original Article Series, Vol 23, No 2 1987) by Gerry Evers-Kiebooms (Editor), et al; ISBN: 0471633364; http://www.amazon.com/exec/obidos/ASIN/0471633364/icongroupinterna

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Genetic Services for Underserved Populations: Proceedings (Birth Defects Original Article Series, Vol 26, No 2) by Natalie Paul, Laura Kavanagh (Editor) (1990); ISBN: 9991647260; http://www.amazon.com/exec/obidos/ASIN/9991647260/icongroupinterna

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Genetic Susceptibility to Environmental Mutagens and Carcinogens (Birth Defects Original Article Series Vol 25 No 2); ISBN: 9991647597; http://www.amazon.com/exec/obidos/ASIN/9991647597/icongroupinterna

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Genetics and Birth Defects in Clinical Practice by Murray Feingold, et al; ISBN: 0316277150; http://www.amazon.com/exec/obidos/ASIN/0316277150/icongroupinterna

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Genetics of Hand Malformations (Birth Defects Original Article Series, Vol Xiv, No 3) by Samia A. Tentamy, et al; ISBN: 0471504831; http://www.amazon.com/exec/obidos/ASIN/0471504831/icongroupinterna

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Growth Problems and Clinical Advances (Birth Defect Series, No. 6) by Bergsma; ISBN: 0471562912; http://www.amazon.com/exec/obidos/ASIN/0471562912/icongroupinterna

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Healthy Baby Book: A Parent's Guide to Preventing Birth Defects and Other Long Term Medical Problems Before, During and After Pregnancy by Carolyn Reuben; ISBN: 0874776791; http://www.amazon.com/exec/obidos/ASIN/0874776791/icongroupinterna

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Human Gene Mapping (Birth Defects Original Article Series Vol 25 No 3) (1988); ISBN: 9991647856; http://www.amazon.com/exec/obidos/ASIN/9991647856/icongroupinterna

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Human Gene Mapping, 7: Los Angeles Conference (1983): Seventh International Workshop on Human Gene Mapping: At the University of California, Los Angeles (Ucla), August (Birth Defects Original Article Series, V. 20, No. 2.) by Calif. International Workshop on Human Gene Mapping 1983 Los Angeles, et al (1984); ISBN: 3805538405; http://www.amazon.com/exec/obidos/ASIN/3805538405/icongroupinterna

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Human Heredity and Birth Defects by Erminio Peter. Volpe; ISBN: 0672535491; http://www.amazon.com/exec/obidos/ASIN/0672535491/icongroupinterna

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In vitro epithelia and birth defects : proceedings of the workshop "Study of human birth defects using cultured epithelium" held at the Johns Hopkins Turner Auditorium in Baltimore, Maryland; ISBN: 0845110365; http://www.amazon.com/exec/obidos/ASIN/0845110365/icongroupinterna

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Infertility and Birth Defects: Is Mercury from Silver Dental Fillings an Unsuspected Cause by Sam Ziff, Michael F. Ziff (1988); ISBN: 0941011038; http://www.amazon.com/exec/obidos/ASIN/0941011038/icongroupinterna

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International Nomenclature of Constitutional Diseases of Bones (Birth Defects Original Article Series, Vol 22, No 4); ISBN: 9997489640; http://www.amazon.com/exec/obidos/ASIN/9997489640/icongroupinterna

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Is My Baby All Right? a Guide to Birth Defects, by Virginia. Apgar; ISBN: 0671270958; http://www.amazon.com/exec/obidos/ASIN/0671270958/icongroupinterna

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Life and Death Decisions: Help in Making Tough Choices About Infertility, Abortion, Birth Defects, and AIDS by Robert D. Orr, et al; ISBN: 080105270X; http://www.amazon.com/exec/obidos/ASIN/080105270X/icongroupinterna

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Medical and Experimental Mammalian Genetics: A Perspective (Birth Defects Original Article Series, Vol 23, No 3 1987) by Victor A. McKusick; ISBN: 0471637866; http://www.amazon.com/exec/obidos/ASIN/0471637866/icongroupinterna

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Minor Birth Defects/Slides by Jackie A. Simmons; ISBN: 091675037X; http://www.amazon.com/exec/obidos/ASIN/091675037X/icongroupinterna

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Monitoring, Birth Defects and Environment: The Problem of Surveillance; Proceedings. by Ernest B. and Et Al Hook; ISBN: 0123554500; http://www.amazon.com/exec/obidos/ASIN/0123554500/icongroupinterna

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Natural history of specific birth defects; ISBN: 0845110128; http://www.amazon.com/exec/obidos/ASIN/0845110128/icongroupinterna

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Natural History of Specific Birth Defects (Alan R. Liss Series: Vol 13 No 3C) by Daniel Bergsma (Editor) (1977); ISBN: 0686231228; http://www.amazon.com/exec/obidos/ASIN/0686231228/icongroupinterna

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Neural and Behavioural Teratology (Advances in the Study of Birth Defects) by T.V.N. Persaud (Editor); ISBN: 0852002815; http://www.amazon.com/exec/obidos/ASIN/0852002815/icongroupinterna

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NYHAN ANNUAL REVIEW OF BIRTH DEFECTS 1981 - PART A PRE DIA & MEC OF TER - PART B DYSMORPHO by WL NYHAN; ISBN: 0845109545; http://www.amazon.com/exec/obidos/ASIN/0845109545/icongroupinterna

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Nyhan Birth Defects by NYHAN; ISBN: 0471613940; http://www.amazon.com/exec/obidos/ASIN/0471613940/icongroupinterna

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PAUL CUMULATIVE INDEX - BIRTH DEFECTS - ORIGINAL ARTICLES SERIES VOLS 1(1965) - 16(1980) by NW PAUL; ISBN: 0471565903; http://www.amazon.com/exec/obidos/ASIN/0471565903/icongroupinterna

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Perinatal Genetics: Diagnosis and Treatment (Birth Defects Institute Symposia) by Ian H. Porter, et al; ISBN: 0125628552; http://www.amazon.com/exec/obidos/ASIN/0125628552/icongroupinterna

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Practical Guide to Cleft Lip and Palate Birth Defects: Helpful, Practical Information and Answers for Parents, Physicians, Nurses and Other Profess by Sidney K. Wynn, Miller Alfred Wynn; ISBN: 0398050244; http://www.amazon.com/exec/obidos/ASIN/0398050244/icongroupinterna

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Prevention in Prenatal Nursing (March of Dimes Birth Defects Series, Vol 27, Part 3) (1991); ISBN: 9992255862; http://www.amazon.com/exec/obidos/ASIN/9992255862/icongroupinterna

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Problems of birth defects : from Hippocrates to thalidomide and after : original papers with commentaries by T. V. N. Persaud; ISBN: 0852001509; http://www.amazon.com/exec/obidos/ASIN/0852001509/icongroupinterna

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Problems of Birth Defects, from Hippocrates to Thalidomide and After: Original Papers by Bal; ISBN: 0839111398; http://www.amazon.com/exec/obidos/ASIN/0839111398/icongroupinterna

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Program Strategies for Preventing Fetal Alcohol Syndrome and Alcohol-Related Birth Defects; ISBN: 0318229358; http://www.amazon.com/exec/obidos/ASIN/0318229358/icongroupinterna

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Prospective Studies on Children With Sex Chromosome Aneuploidy (Birth Defects: Original Article Series, Vol 22, No 3) by Shirley G. Rattcliffe, et al; ISBN: 0471625094; http://www.amazon.com/exec/obidos/ASIN/0471625094/icongroupinterna

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Protecting Your Baby-To-Be: Preventing Birth Defects in the First Trimester by Margie Profet, Mary Krikorian (Illustrator); ISBN: 020140768X; http://www.amazon.com/exec/obidos/ASIN/020140768X/icongroupinterna

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Recent Advances in Ectodermal Dysplasias (Birth Defects, Original Article Series, Vol 24, No 2) by Carlos F. Salinas (Editor), et al; ISBN: 0471501069; http://www.amazon.com/exec/obidos/ASIN/0471501069/icongroupinterna

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Reducing American Exposure to Nitrate Nitrite and Nitroso Compounds: The National Network to Prevent Birth Defects Proposal (Comments from Cast, 198) by Charles A. Black (1989); ISBN: 9999222986; http://www.amazon.com/exec/obidos/ASIN/9999222986/icongroupinterna

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Reducing the Impact of Birth Defects: Meeting the Challenges in the Developing World by Judith R. Bale (Editor), et al (2003); ISBN: 0309086086; http://www.amazon.com/exec/obidos/ASIN/0309086086/icongroupinterna

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Reincarnation and Biology : A Contribution to the Etiology of Birthmarks and Birth Defects Volume 2: Birth Defects and Other Anomalies by Ian Stevenson (Author) (1997); ISBN: 0275952843; http://www.amazon.com/exec/obidos/ASIN/0275952843/icongroupinterna

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Research and Clinical Aspects of the Late Effects of Poliomyelitis (Birth Defects Original Article Series, Vol 23, No 4) by Lauro S. Halstead, David O. Wiechers (Editor); ISBN: 9998729238; http://www.amazon.com/exec/obidos/ASIN/9998729238/icongroupinterna

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Research and Infant Assessment (Birth Defects Original Article Series, Vol 25, No 6, 1989) (1989); ISBN: 9991647333; http://www.amazon.com/exec/obidos/ASIN/9991647333/icongroupinterna

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Retinopathy of Prematurity: Problem and Challenge (Birth Defects Original Article Series, Vol 24, No 1) by John T. Flynn (Editor), Dale L. Phelps (Editor); ISBN: 0471614386; http://www.amazon.com/exec/obidos/ASIN/0471614386/icongroupinterna

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Service and education in medical genetics : proceedings of the Seventh Annual New York State Health Department Birth Defects Symposium; ISBN: 0125626509; http://www.amazon.com/exec/obidos/ASIN/0125626509/icongroupinterna

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Social Support and Families of Vulnerable Infants (Birth Defects Original Article Series Vol 20 No 5 1983) by Kathryn E. Barnard; ISBN: 0865250308; http://www.amazon.com/exec/obidos/ASIN/0865250308/icongroupinterna

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Strategies in Genetic Counseling: Clinical Investigation Studies (Birth Defects Original Article Series, Vol. 20, No 6) by Beth A. Fine (Editor) (1984); ISBN: 9996567478; http://www.amazon.com/exec/obidos/ASIN/9996567478/icongroupinterna

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Strategies in Genetic Counseling: Issues in Perinatal Care: Religious, Cultural and Ethnic Influences (Birth Defects Original Article Series, 23-6) (1987); ISBN: 9998729203; http://www.amazon.com/exec/obidos/ASIN/9998729203/icongroupinterna

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Strategies in Genetic Counseling: Reproductive Genetics and New Technology (Birth Defects Original Article Series, Vol 26, No 3) by Beth A. Fine, et al (1990); ISBN: 9991648062; http://www.amazon.com/exec/obidos/ASIN/9991648062/icongroupinterna

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Teratogen update : environmentally induced birth defect risks; ISBN: 0845142089; http://www.amazon.com/exec/obidos/ASIN/0845142089/icongroupinterna

134 Birth Defects

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Teratogen Update: Environmentally Induced Birth Defect Risks by John L. Sever (Editor), Robert L. Brent (Editor); ISBN: 0471860115; http://www.amazon.com/exec/obidos/ASIN/0471860115/icongroupinterna

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Teratogenic Mechanisms (Advances in the Study of Birth Defects) by T.V.N. Persaud (Editor); ISBN: 0852002106; http://www.amazon.com/exec/obidos/ASIN/0852002106/icongroupinterna

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Teratogens: Chemicals Which Cause Birth Defects by Vera M. Kolb (Editor); ISBN: 0444814825; http://www.amazon.com/exec/obidos/ASIN/0444814825/icongroupinterna

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Teratogens: Chemicals Which Cause Birth Defects (Studies in Environmental Science, 31) by Vera Kolb Meyers (Editor); ISBN: 044442914X; http://www.amazon.com/exec/obidos/ASIN/044442914X/icongroupinterna

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Teratological Testing (Advances in the Study of Birth Defects) by T.V.N. Persaud (Editor); ISBN: 0852002718; http://www.amazon.com/exec/obidos/ASIN/0852002718/icongroupinterna

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Thalassemia: Pathophysiology and Management, Part a (Birth Defects: Original Article Series, Vol 23, No 5A, 1987) by Suthat Fucharoen (Editor), et al; ISBN: 0471606383; http://www.amazon.com/exec/obidos/ASIN/0471606383/icongroupinterna

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Thalassemia: Pathophysiology and Management, Part B (Birth Defects: Original Article Series, Vol 23 No 5B) by Suthat Funcharoen (Editor), Rowley; ISBN: 0471610437; http://www.amazon.com/exec/obidos/ASIN/0471610437/icongroupinterna

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The Child with Multiple Birth Defects by M. Michael, Jr. Cohen; ISBN: 0195099265; http://www.amazon.com/exec/obidos/ASIN/0195099265/icongroupinterna

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The Cost of Birth Defects by Norman J. Waitzman, et al; ISBN: 0761802487; http://www.amazon.com/exec/obidos/ASIN/0761802487/icongroupinterna

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The fifth Conference on the Clinical Delineation of Birth Defects : [proceedings]; ISBN: 0882753533; http://www.amazon.com/exec/obidos/ASIN/0882753533/icongroupinterna

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The Patient Within the Patient: Problems in Perinatal Medicine (Birth Defects: Original Article Series, Vol 21, No 5) by Bruce K. Young (Editor); ISBN: 047184375X; http://www.amazon.com/exec/obidos/ASIN/047184375X/icongroupinterna

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Transplacental Disorders: Perinatal Detection, Treatment, and Mangement: Proceedings of the 1988 Albany Birth Defects Symposium Xix, Sept 1988 by Gerald J. Mizejewski (Editor), Ronald J. Bellisario (Editor); ISBN: 0471566772; http://www.amazon.com/exec/obidos/ASIN/0471566772/icongroupinterna

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Understanding Birth Defects (Single Titles Series) by Karen Gravelle; ISBN: 0531109550; http://www.amazon.com/exec/obidos/ASIN/0531109550/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search

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area, simply type “birth defects” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:9 •

Birth defects. Author: Fishbein, Morris,; Year: 1963; Philadelphia, Lippincott [c1963]

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Congenital malformations; proceedings of the third International Conference. The Hague, The Netherlands, 7-13 September 1969. Sponsored by the National Foundation - March of Dimes and organized by International Medical Congress ltd. on the general theme of Birth defects-1969. Editors: F. Clarke Fraser [and] Victor A. McKusick. Co-editor: Roger Robinson. Author: Fraser, F. Clarke,; Year: 1970; Amsterdam, New York, Excerpta Medica Foundation [1970]; ISBN: 9021901358

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Genetic counseling; with particular reference to anticipatory guidance and the prevention of birth defects. Harold Abramson, chairman. Editor: Daniel Bergsma; guest editor: Harold Abramson; assistant editors: Camille Jackson [and] Margaret Muserlian. Author: Abramson, Harold A. (Harold Alexander),; Year: 1970; Baltimore, Williams and Wilkins, 1970; ISBN: 683063456

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Genetic mechanisms of sexual development: proceedings of a symposium sponsored by the Birth Defects Institute of the New York State Dept. of Health, and held in Albany, N. Y., Nov. 8-9, 1976. Author: Porter, Ian H.; Year: 1979; New York: Academic Press, 1979; ISBN: 0127105506 http://www.amazon.com/exec/obidos/ASIN/0127105506/icongroupinterna

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Human heredity and birth defects. Author: Volpe, E. Peter (Erminio Peter); Year: 1971; New York, Bobbs-Merrill [c1971]

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Monitoring, birth defects, and environment; the problem of surveillance. Edited by Ernest B. Hook, Dwight T. Janerich [and] Ian H. Porter. Assistant editors: Sally Kelly [and] Richard G. Skalko. Author: Hook, Ernest B.; Year: 1971; New York, Academic Press, 1971

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New chromosomal and malformation syndromes: the 1974 Birth Defects Conference held at Newport Beach, California Author: Bergsma, Daniel,; Year: 1975; New York: Stratton Intercontinental Medical Book Corp., c1975; ISBN: 0883720329 http://www.amazon.com/exec/obidos/ASIN/0883720329/icongroupinterna

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Symposium on the placenta, its form and functions, with particular reference to the prevention of birth defects and fetal deaths. Author: Medical Society of the County of New York. Special Committee on Infant Mortality.; Year: 1965; [New York, National Foundation, c1965]

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The fifth Conference on the Clinical Delineation of Birth Defects. Editor: Daniel Bergsma; associate editors: Victor A. McKusick [et al.]; assistant editors: Camille Jackson [and] Sue Conde. Author: Bergsma, Daniel,; Year: 1974; Baltimore, Published for the National Foundation-March of Dimes by Williams and Wilkins, 1974-; ISBN: 0683063650

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The first Conference on the Clinical Delineation of Birth Defects. Editor: Daniel Bergsma; associate editors: Victor A. McKusick [et al.] assistant editor: Camille

9

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

136 Birth Defects

Jackson [et al. Author: Bergsma, Daniel,; Year: 1969; New York, National Foundation] 1969 •

The fourth Conference on the Clinical Delineation of Birth Defects. Editor: Daniel Bergsma; associate editors: Victor A. McKusick [et al.]; assistant editors: Camille Jackson [and] Sue Ellen Conde. Author: Bergsma, Daniel,; Year: 1972; Baltimore, Published for the National Foundation-March of Dimes by Williams and Wilkins, 1972; ISBN: 0683063626 http://www.amazon.com/exec/obidos/ASIN/0683063626/icongroupinterna

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The second Conference on the Clinical Delineation of Birth Defects, the Turner Auditorium, the Johns Hopkins Medical Institutions, Baltimore Maryland, May 26May 30, 1969. Author: Conference on the Clinical Delineation of Birth Defects, 2d, Baltimore, 1969.; Year: 1975; [New York, National Foundation] 1969

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The third Conference on the Clinical Delineation of Birth Defects. Editor: Daniel Bergsma; associate editors: Victor A. McKusick [et al.]: assistant editors: Camille Jackson [and] Marjorie W. Lorber. Author: Bergsma, Daniel,; Year: 1971; Baltimore, Williams and Wilkins, 1971-72; ISBN: 0683063391

Chapters on Birth Defects In order to find chapters that specifically relate to birth defects, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and birth defects 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 “birth defects” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on birth defects: •

Syndromes With Orofacial Clefting Source: in Wyszynski, D.F., ed. Cleft Lip and Palate: From Origin to Treatment. New York, NY: Oxford University Press, Inc. 2002. p. 53-65. Contact: Available from Oxford University Press. Customer Service Department, 2001 Evans Road, Cary, NC 27513. (800) 445-9714. Fax (919) 677-1303. E-mail: [email protected]. Website: www.oup-usa.org. PRICE: $125.00 plus shipping and handling. ISBN: 0195139062. Summary: Cleft lip with or without cleft palate and isolated cleft palate, collectively termed oral clefts, are the second most common birth defects among newborns. This chapter on syndromes with orofacial clefting is from a textbook on cleft lip and palate that covers a broad range of theoretical, experimental, and clinical topics and is written by experts in the fields of craniofacial development, biomedical sciences, genetics, epidemiology, and public health. Topics include syndromes, sequences, and associations; syndrome delineation; the process of syndrome delineation; syndrome nomenclature; Robin sequence and Robin complexes; and unusual craniofacial clefts and the Tessier classification. 16 figures. 6 tables. 35 references.

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How Does Diabetes Affect Pregnancy? Source: in Hirsch, I.B. 12 Things You Must Know About Diabetes Care Right Now!. Alexandria, VA: American Diabetes Association. 2000. p. 61-75.

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Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400612. Summary: This chapter discusses the impact of preexisting and gestational diabetes on pregnancy. Pregnant women who have diabetes are classified into those who had diabetes before pregnancy and those whose diabetes developed during pregnancy. Both type 1 and type 2 diabetes can affect fetal development. Thus, good diabetes control is important to reduce complications in the baby. Possible complications of preexisting diabetes include miscarriage and birth defects. Adolescents and women in their childbearing years should discuss contraceptive needs and concerns about a future pregnancy with their health care team. Women who are taking oral medications for diabetes need to stop using these drugs before they become pregnant. During pregnancy, women need to undergo various tests to determine risks to both them and their infant. Other issues confronting pregnant women with preexisting diabetes include emotional stress, life expectancy, the impact of pregnancy on eye problems and kidney disease, and home testing of blood glucose and urine. Gestational diabetes develops in 2 to 3 percent of pregnant women. Screening is recommended for all pregnant women except those in the low risk group at 24 to 28 weeks after conception. If gestational diabetes is diagnosed and managed properly, there are few complications. Women diagnosed with gestational diabetes need to achieve normal blood glucose levels and eat enough good foods. Women may avoid unplanned pregnancies by using some form of contraception, including the pill, Norplant, Depo-Provera, the diaphragm, condoms, intrauterine devices, the rhythm method, and sterilization. 4 tables. •

Nutrition Therapy for Pregnancy and Lactation Source: in Franz, M.J. and Bantle, J.P., eds. American Diabetes Association Guide to Medical Nutrition Therapy for Diabetes. Alexandria, VA: American Diabetes Association. 1999. p. 229-248. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 for members; $49.95 for nonmembers; plus shipping and handling. ISBN: 158040006X. Order number 561601. Summary: This chapter focuses on nutrition issues associated with pregnancy and breastfeeding. Nutrition related concerns during pregnancy include weight gain and caloric requirements, adequate nutrients, and possible need for vitamin and mineral supplements such as iron and folic acid. The problems associated with pregnancy in women with diabetes include an increased risk for fetal birth defects and increased spontaneous abortion rates. Nutrition therapy for women who have prior onset type 1 or type 2 diabetes begins with a prenatal meal plan before attempting conception so that they can attempt to achieve glycemic control and optimal body weight. The goal of medical nutrition therapy (MNT) in a pregnancy with diabetes is to maintain normal blood glucose levels while meeting the nutritional needs of pregnancy. Regular meals and snacks are very important to avoid hypoglycemia during pregnancy. Breastfeeding is recommended for women who have diabetes, and a postpartum meal plan must account for the energy demands of breastfeeding as well as its lowering effects on blood glucose. For women who develop gestational diabetes mellitus (GDM), MNT is used to achieve optimal blood glucose control with adequate nutrition for both mother and fetus. Intensive nutrition therapy, along with daily blood glucose monitoring and an exercise program, may be an alternative to insulin therapy in women who develop

138 Birth Defects

GDM. Breastfeeding is also encouraged in women who have GDM. Women should not follow a hypocaloric diet until lactation is terminated. 1 figure. 6 tables. 63 references. •

Basic Genetic Concepts in Craniofacial Anomalies Source: in Bzoch, K.R., ed. Communicative Disorders Related to Cleft Lip and Palate. 4th ed. Austin, TX: PRO-ED, Inc. 1997. p. 69-94. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (512) 451-3246. Fax (800) 397-7633. PRICE: $56.70 plus shipping and handling. ISBN: 0890797013. Summary: This chapter on basic genetic concepts in craniofacial anomalies is from a textbook that explores cleft lip and cleft palate and the communicative disorders that can result from these conditions. The authors begin by noting that cleft lip and palate provide an excellent teaching example for consideration of how concepts have changed over the past decade regarding the frequency with which birth defects occur in combination rather than in isolation and how the presence of concurrent defects changes the understanding of the cleft or other defects. After a section on terminology, the authors offer a detailed introduction to human genetics and to medical genetics. The chapter concludes with a discussion of specific examples of craniofacial defects, including achondroplasia, Apert syndrome, Crouzon syndrome, EEC syndrome, Freeman-Sheldon syndrome, Melnick-Fraser syndrome (branchio-oto-renal), Pfeiffer syndrome, Saethre-Chotzen syndrome, Stickler syndrome, Treacher Collins syndrome, Van der Woude syndrome, velocardiofacial syndrome, and Waardenburg syndrome. Photographs of children with these syndromes are included throughout the chapter. The authors conclude by encouraging professionals in clinical practice, particularly those working with young children, to avail themselves of a library in which illustrated references on birth defects are maintained on a current basis. 19 figures. 3 tables. 45 references.

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Health Supervision for Children with Neurofibromatosis Source: in Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner. Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. p. 30-34. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number BMA0097. Summary: This chapter on health supervision for children with neurofibromatosis is from a compendium of the American Academy of Pediatrics (AAP) guidelines and resources for pediatricians and primary care physicians who are working with patients who have genetic disorders and birth defects. The compendium serves as a diagnostic and management resource guide for pediatricians and primary care physicians. This chapter offers guidelines designed to assist the pediatrician in caring for the child in whom the diagnosis of neurofibromatosis has been made. The introductory section reviews the symptoms and complications of neurofibromatosis (focusing on type 1, the non-acoustic type), genetic considerations, and general clinical management of these patients. The Policy Statement then outlines strategies to adopt for the prenatal visit (some pregnant women are referred for consultation), health supervision for newborns (birth to one month), infants (one month to one year), early childhood (one to five

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years), late childhood (five to thirteen years), and adolescent to early adulthood (thirteen years to twenty-one years or older). Each section notes recommendations for examination and anticipatory guidance. Complications in neurofibromatosis type 1 including learning problems, speech disorders, hyperactivity, increased risk for malignancy, and neurologic and vascular changes. 24 references.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to birth defects have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:10 •

Parent Resources: Agencies, Organizations, Support Groups Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 213-234. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: This appendix section is from a parent education skill builders textbook. The appendix lists agencies, organizations, and support groups that parents might want to contact as they work with developing communication skills in and with their child. National information and advocacy groups are listed, including groups for consumer information, education, financial aid, home care, legal assistance, nonoral communication, orthotics and prosthetics, psychiatry, psychology, rare disorders, rehabilitation, residential placement, self-help, severe disabilities, sibling support, social workers, and telephone usage for persons with disabilities. Also listed are national organizations for specific disabilities and conditions, including acoustic neuroma, autism, birth defects, chronic dizziness and balance disorders, cleft palate and craniofacial disorders, developmental disabilities, Down's syndrome, dyslexia, dystonia, genetic conditions, head injuries, hearing impairments, learning disabilities, mental retardation, neurofibromatosis, neurological disorders, stuttering, Tourette syndrome, and voice disorders and laryngectomies. The address and telephone number for each organization are noted.

•

Directory of national voluntary genetic organizations and related resources. (2nd ed.) Source: Chevy Chase, MD: Alliance of Genetic Support Groups. 1995. 178 pp. Contact: Available from Alliance of Genetic Support Groups, 4301 Connecticut Avenue, N.W., Suite 404, Washington, DC 20008-2304. Telephone: (202) 966-5557 or (800) 336GENE / fax: (301) 654-0171 / e- mail: [email protected] / Web site: http://www.geneticalliance.org. $20.00 plus $2.00 shipping and handling; prepayment required.

10

You will need to limit your search to “Directory” and “birth defects” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “birth defects” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

140 Birth Defects

Summary: This directory provides a listing and description of mutual support groups concerned with the medical and psychosocial impacts of genetic disorders and birth defects on affected individuals and families. This directory is arranged according to categories of disorders, and contains an organizational index and subject index as well. The directory is based upon the 'Guide to Selected National Genetic Voluntary Organizations.' In 1996, the directory was made available online at http://medhlp.netusa.net/www/agsg.htm.

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CHAPTER 7. MULTIMEDIA ON BIRTH DEFECTS Overview In this chapter, we show you how to keep current on multimedia sources of information on birth defects. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on birth defects is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “birth defects” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “birth defects” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on birth defects: •

Hearing Disorders: A Guide to Self-Health Source: Evanston, IL: Altscul Group Corporation. 1994. (videocassette). Contact: Available from Altschul Group Corporation. 1560 Sherman Avenue, Suite 100, Evanston, IL 60201. Voice (800) 323-9084 or (708) 328-6700; Fax (708) 328-6706. PRICE: $179.00 plus shipping and handling. Summary: This videotape program presents a guide to self-health in the area of hearing disorders. Topics covered include how humans perceive sound; the physics of sound; the structure of the human ear; the origins of hearing loss, including birth defects, disease, and environmental causes; hearing aids; and other technological advances. The program emphasizes that most hearing disorders cannot be cured, but coping methods and therapies are available. The videotape is part of a series on disease prevention that emphasizes lifestyle and environmental factors which increase the risk of illness. At the same time, these programs illustrate the impact of health problems on individuals and

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society. Each program provides viewers with a better understanding of bodily functions and helps them to detect signs or symptoms of eventual illness. (AA-M).

Bibliography: Multimedia on Birth Defects The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in birth defects (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on birth defects: •

Birth defects [electronic resource]. Year: 1986; Format: Electronic resource; Fairfield, CT: Queue, c1986

•

Birth defects and common drugs [slide] Source: David J. Gerrick; Year: 1980; Format: Slide; [Lorain, OH]: Dayton Lab, c1980

•

Birth defects and dermatoglyphics [slide] Source: David J. Gerrick; Year: 1979; Format: Slide; Lorain, OH: Dayton Lab, c1979

•

Birth defects research. Part A, Clinical and molecular teratology. Year: 9999; Hoboken, N.J.: John Wiley & Sons, [2003-

•

Birth defects research. Part B, Developmental and reproductive toxicology. Year: 9999; Hoboken, N.J.: Wiley-Liss, c2003-

•

Birth defects tracking and prevention [electronic resource]: too many states are not making the grade. Year: 2002; Format: Electronic resource; [S.l.]: Trust for America's Health, 2002

•

Minor birth defects [slide] David J. Gerrick. Year: 1980; Format: Slide; Lorain, OH: Dayton Lab, c1980

•

Pesticide exposure [videorecording]: cancer and birth defects Source: [presented by] Agromedicine Program; Health Communication [s] Network production; Year: 1990; Format: Videorecording; Charleston, S.C.: MUSC-HCN, c1990

•

Prenatal diagnosis of birth defects by ultrasound [videorecording] Source: produced by the University of Texas Health Science Center at Dallas, Dept. of Biomedical Communications, in association with Gene Team Productions; Year: 1980; Format: Videorecording; Dallas, Tex.: UTHSCD, c1980

•

Risks of agent orange and birth defects [videorecording] Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1984; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1984

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CHAPTER 8. PERIODICALS AND NEWS ON BIRTH DEFECTS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover birth defects.

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

Magnets repair birth defect in food pipe Source: Reuters Health eLine Date: September 26, 2003

•

Living near incinerator may up birth defect risk Source: Reuters Health eLine Date: May 29, 2003

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•

Vitamins may cut risk of birth defects in diabetics Source: Reuters Health eLine Date: May 26, 2003

•

Obesity before pregnancy ups risk of birth defects Source: Reuters Health eLine Date: May 05, 2003

•

Antidepressant use not linked to birth defects Source: Reuters Health eLine Date: April 23, 2003

•

Risk of Down syndrome linked to other birth defects Source: Reuters Health eLine Date: April 18, 2003

•

Genetic test averts birth defect disorder in baby Source: Reuters Health eLine Date: April 09, 2003

•

Study links common plastic to birth defects Source: Reuters Health eLine Date: March 31, 2003

•

IVF and rare urologic birth defect may be linked Source: Reuters Health eLine Date: March 21, 2003

•

Gene linked to birth defect syndroMen Source: Reuters Health eLine Date: February 07, 2003

•

Maurice Gibb's death blamed on birth defect Source: Reuters Health eLine Date: January 17, 2003

•

Pre-pregnancy diabetes ups risk of birth defects Source: Reuters Health eLine Date: November 07, 2002

•

Birth defect gene sheds light on brain formation Source: Reuters Health eLine Date: October 02, 2002

•

Extra folic acid cuts birth defect rate in Canada Source: Reuters Health eLine Date: September 09, 2002

•

Birth defect risk unknown for most new drugs Source: Reuters Health eLine Date: September 02, 2002

•

Timing of sex doesn't affect risk of birth defects Source: Reuters Health eLine Date: May 10, 2002

•

Aging gametes not linked to increased birth defect risk Source: Reuters Medical News Date: May 10, 2002

Periodicals and News

•

Prenatal vitamins cut risk for rare birth defect Source: Reuters Health eLine Date: May 07, 2002

•

Loratidine linked to birth defects in Europe Source: Reuters Medical News Date: April 25, 2002

•

EMEA looking into potential link between loratadine, birth defect Source: Reuters Industry Breifing Date: April 25, 2002

•

DES linked to birth defect in grandsons Source: Reuters Health eLine Date: March 29, 2002

•

Birth defects on the rise in Britain-newspaper Source: Reuters Health eLine Date: March 18, 2002

•

Test-tube babies may face higher birth defect risk Source: Reuters Health eLine Date: March 06, 2002

•

Infertility therapy linked to birth defects and low-birth-weight infants Source: Reuters Medical News Date: March 06, 2002

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

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “birth defects” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on birth defects: •

Craniofacial Program: When Your Child Needs Very Specialized Care Source: Inova HealthSource. p. 4-5. Spring 2001. Contact: Available from Inova Health System. 2832 Juniper Street, Fairfax, VA 22031. Summary: This brief article describes the patient care team that may be used to help care for a child who needs specialized craniofacial treatment. Most of these children will have been born with a cleft lip or palate; a smaller number have other abnormalities of the face or skull. These birth defects can be disfiguring and result in other health and developmental problems. A treatment team composed of experts from a variety of disciplines provides comprehensive care for children born with craniofacial abnormalities. The team evaluates and treats children in one central location so parents do not have to spend added time going from specialist to specialist. Sidebars to the article describe some of the services available from the Craniofacial Program at Inova Fairfax Hospital for Children (and their contact number is provided). The latter half of the article offers the story of one family's experience with a craniofacial care team for their child who was born with a cleft lip and palate.

Periodicals and News

•

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Clefts of the Lip and Palate Source: Faces. 8(2): no page nos. Spring 1994. Contact: Available from National Association for the Craniofacially Handicapped. P.O. Box 11082, Chattanooga, TN 37401. (615) 266-1632 or (800) 332-2373. Summary: This newsletter article provides an overview of clefts of the lip and palate, relatively common birth defects occurring in both males and females of all races. Topics covered include unilateral cleft lip; bilateral cleft lip; cleft palate; and late cleft treatment. The author focuses on the surgical correction of lip and palate clefts, stressing the important role of the craniofacial team in diagnosis and treatments of these anomalies. Photographs of four children before and after reconstructive surgery are included.

•

Accutane Risk Management Program Strengthened Source: FDA Consumer. 36(1): 8. January-February 2002. Contact: Available from Superintendent of Documents. Government Printing Office, Washington, DC 20402. (202) 512-1800. Summary: This newsletter article provides health professionals and pregnant women who have severe acne with information on a new risk management program for Accutane. The new program is called the System to Manage Accutane Related Teratogenicity (S.M.A.R.T.). Although Accutane is a very effective treatment for severe acne, its use has significant potential risks, including birth defects and fetal death. The program was developed to ensure that no woman begins Accutane therapy if she is pregnant and that no pregnancy occurs while a woman is taking Accutane. The program requires that doctors who prescribe Accutane must study the S.M.A.R.T. 'Guide to Best Practices' provided by the manufacturer and then sign and return a letter certifying their knowledge of the measures to minimize fetal exposures to Accutane. In addition, all female patients must have two negative urine or serum pregnancy tests before the initial Accutane prescription is written, and pharmacists will dispense Accutane only if a prescription has the special Accutane qualification sticker.

•

Power of Accutane, The Source: FDA Consumer. 35(2): 18-23. March-April 2001. Contact: Available from Superintendent of Documents. Government Printing Office, Washington, DC 20402. (202) 512-1800. Summary: This newsletter article provides people who have severe acne with information on the use of accutane to clear the condition. Accutane is the only drug that has the potential to clear severe acne permanently after 5 months of treatment. However, its adverse effects can be as powerful as its benefits. The drug is known to cause miscarriage and severe birth defects such as hydrocephaly, microcephaly, heart problems, facial deformities, and mental retardation; problems with the liver, intestines, eyes, ears, and skeletal system; and psychiatric difficulties. Therefore, Accutane should be reserved for cases of severe recalcitrant nodular acne. Women taking the drug need to comply with contraceptive requirements because of the teratogenicity of the drug. The manufacturer launched the Pregnancy Prevention Program (PPP) in late 1998 to further educate women using Accutane and their physicians about its dangers. Despite claims by the manufacturer that pregnancy rates among Accutane users have declined as a result of the program, substantial noncompliance with the PPP continues to be reported. Another adverse effect, the development of psychiatric disorders such as

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depression and psychosis, has not been conclusively proven, but the Food and Drug Administration considers the number of reports of serious depression associated with Accutane high compared with other drugs. 4 figures.

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

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for birth defects. 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 birth defects. 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 birth defects: Acitretin •

Systemic - U.S. Brands: Soriatane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203365.html

Folic Acid (Vitamin B 9 ) •

Systemic - U.S. Brands: Folvite http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202250.html

Isotretinoin •

Systemic - U.S. Brands: Accutane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202309.html

Thalidomide •

Systemic - U.S. Brands: THALOMID http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202692.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

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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

155

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

Physician Resources

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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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “birth defects” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “birth defects” (or synonyms) into the “For these words:” box. The following is a sample result: •

March of Dimes: Preventing Birth Defects Contact: March of Dimes Birth Defects Foundation, National Office, 1275 Mamaroneck Ave, White Plains, NY, 10605, (914) 428-7100. Summary: This information package contains materials related to Acquired immunodeficiency syndrome (AIDS) in children. They include a brochure, "Building Systems of Care for Children With HIV Infection & Their Families," which looks at Human immunodeficiency virus (HIV) transmission, pediatric AIDS activities, and the initiative on pediatric AIDS and HIV diseases; a videorecording, "AIDS: A Health Crisis for the Century, Implications for Obstetric & Gynecologic Care" with an accompanying post-test; a research article titled "AIDS in Children"; and a bibliography of related materials. Contains graphics of the HIV.

•

Healthy from the start: Why America needs a better system to track and understand birth defects and the environment Source: Baltimore, MD: Pew Environmental Health Commission. [1999]. 86 pp. Contact: Available from Pew Environmental Health Commission, Johns Hopkins School of Public Health, 111 Market Street, Suite 850, Baltimore, MD 21202. Available from the Web site at no charge. Summary: This report examines the need for a comprehensive, modern tracking system to identify environmental and other preventable factors that contribute to birth defects and other disabilities and preventable diseases. The first section of the report discusses the connection between environmental exposures and birth defects, preterm and low birthweight, cerebral palsy, mental retardation and autism. The second section analyzes existing information from the National Center for Health Statistics and state birth defects registries to understand the rates and time trends of infant mortality, low birthweight, preterm birth, and birth defects and the geographic variability of birth defects in the United States. The third section of the report examines the adequacy, comprehensiveness, and quality of state birth defects surveillance systems.

Physician Resources

•

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Birth defects tracking and prevention: Too many states are not making the grade Source: Washington, DC: Trust for America's Health. 2002. 33 pp. Contact: Available from Trust for America's Health, 1101 Vermont Avenue, N.W., Suite 501, Washington, DC 22205. Telephone: (202) 589-0940 / fax: (202) 589-0945 / e-mail: [email protected] / Web site: http://healthyamericans.org. Available from the Web site at no charge. Summary: This report grades each of the 50 states, plus the District of Columbia and Puerto Rico, on their efforts to monitor and research birth defects. The report includes an executive summary; an analysis of the national statistics on birth defects; a discussion of the grading system; conclusions; and recommendations. Extensive appendices outline estimated lifetime costs of selected birth defects; the top 20 pesticides recognized or suspected developmental toxicants; programs with environmental exposure studies; standards; definitions; state-by-state evaluations of minimum national standards; and state monitoring programs and registries. References conclude the report.

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 “birth defects” (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 335368 4158 1230 228 13 340997

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 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

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

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AHRQ’s Put Prevention Into Practice.18 Simply search by “birth defects” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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/.

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

The Genome Project and Birth Defects In the following section, we will discuss databases and references which relate to the Genome Project and birth defects.

18 Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “birth defects” (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 birth defects: •

DiGeorge Syndrome; DGS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?188400

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Absence Defect of Limbs, Scalp, and Skull Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?100300

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Gastroschisis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?230750

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Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?308050

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Beckwith-Wiedemann Syndrome; BWS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?130650

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Noncompaction of Left Ventricular Myocardium with Congenital Heart Defects Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606617

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Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?106260

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Spina Bifida Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?182940

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Leptin; Lep Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?164160

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Velocardiofacial Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?192430

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Oeis Complex Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?258040

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Fibula and Ulna, Duplication of, with Absence of Tibia and Radius Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?135750

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Atrioventricular Septal Defect with Blepharophimosis and Anal and Radial Defects Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600123

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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Diaphragm, Unilateral Agenesis of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?222400

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Renal Dysplasia-Limb Defects Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?266910

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Congenital Heart Defects, Hamartomas of Tongue, and Polysyndactyly Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?217085

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Cerebrocostomandibular Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?117650

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T-Box 1; Tbx1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602054

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Phenylketonuria Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?261600

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Sotos Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?117550

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Angelman Syndrome; AS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?105830

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Cortisol 11-Beta-Ketoreductase Deficiency Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?218030

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Collagen, Type I, Alpha-1; Col1a1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120150

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Cornelia De Lange Syndrome 1; Cdl1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?122470

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Zellweger Syndrome; ZS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?214100

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Kartagener Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?244400

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Roberts Syndrome; RBS Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?268300 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 select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “birth defects” (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 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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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 “birth defects” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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

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Other guides Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Developmental Disabilities http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html

Within the health topic page dedicated to birth defects, the following was listed: •

General/Overviews Descriptions of Leading Categories of Birth Defects Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/aboutus/680_2168.asp

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Diagnosis/Symptoms Amniocentesis Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/159_520.asp Chorionic Villus Sampling (CVS) Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/159_521.asp Ultrasound Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/159_523.asp

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Treatment What Is a Neonatologist? http://www.aap.org/family/WhatisPedNeonatologist.pdf

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Coping Peer Contact for Parents of Children with Congenital Amputations Source: Amputee Coalition of America http://www.amputee-coalition.org/fact_sheets/PC_congenital_amputations.html When Your Baby Has a Birth Defect Source: Nemours Foundation http://kidshealth.org/parent/system/ill/baby_has_birth_defect.html

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Specific Conditions/Aspects Ambiguous Genitalia: When Gender is Unclear at Birth Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=CC00016 Bardet-Biedl Syndrome Source: Foundation Fighting Blindness http://www.blindness.org/visiondisorders/causes.asp?type=9 Birth Defects: Frequently Asked Questions (FAQs) Source: National Center on Birth Defects and Developmental Disabilities http://www.cdc.gov/ncbddd/bd/faq1.htm Cervical Teratoma Source: Children's Hospital Boston http://www.childrenshospital.org/cfapps/A2ZtopicDisplay.cfm?Topic=Cervical% 2520Teratoma Chromosomal Abnormalities Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1209.asp Clubfoot and Other Foot Deformities Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1211.asp Congenital Abnormalities of the Upper Extremity Source: American Society for Surgery of the Hand http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ5QG8UIPC &sub_cat=601 Congenital Diaphragmatic Hernia (CDH) Source: Children's Hospital Boston http://www.childrenshospital.org/cfapps/A2ZtopicDisplay.cfm?Topic=Congenita l%2520Diaphragmatic%2520Hernia%2520%2528CDH%2529 Congenital Torticollis (Twisted Neck) Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=259&topcategory=Neck Craniofacial Syndrome Descriptions Source: Children's Craniofacial Association http://www.ccakids.com/hlpmesyndef.stm Craniosynostosis Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/craniosytosis_doc.htm Crouzon Syndrome (Craniofacial Dysostosis) Source: Cleft Palate Foundation http://www.cleftline.org/publications/cruozon.htm Facing the Challenges: A Guide to Cornelia de Lange Syndrome http://www.cdlsusa.org/pdf/ftc_2001.html FAQs about CdLS Source: Cornelia de Lange Syndrome Foundation http://www.cdlsusa.org/about_cdls/faq.html

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Genital and Urinary Tract Defects Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1215.asp Hearing Loss Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1232.asp Horseshoe Kidney Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00859 Klippel-Feil Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/klippel_feil.htm Late-Appearing Defects Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/4439_4139.asp Mobius Syndrome (Congenital Facial Diplegia) Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/mobius.htm Treacher Collins Syndrome Source: Cleft Palate Foundation http://www.cleftline.org/publications/treacherCollins.htm Undescended Testicles Source: American Academy of Family Physicians http://familydoctor.org/handouts/637.html Waardenburg Syndrome Source: National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/health/hearing/waard.asp What I Need to Know about Hirschsprung's Disease Source: National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/ddiseases/pubs/hirschsprungs_ez/index.htm What is a 'Large (Giant) Congenital Nevus'? Source: Nevus Outreach, Inc. http://www.nevus.org/about/aboutnevi.html •

From the National Institutes of Health Multiple Congenital Anomaly/Mental Retardation Syndromes Database Source: National Library of Medicine http://www.nlm.nih.gov/mesh/jablonski/syndrome_title.html

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Organizations Center for the Evaluation of Risks to Human Reproduction (CERHR) Source: Center for the Evaluation of Risks to Human Reproduction http://cerhr.niehs.nih.gov/ Children's Craniofacial Association http://www.ccakids.com/

Patient Resources

Cornelia de Lange Syndrome Foundation http://www.cdlsusa.org/ March of Dimes Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/ National Center on Birth Defects and Developmental Disabilities Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncbddd/default.htm National Institute of Child Health and Human Development http://www.nichd.nih.gov/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ National Newborn Screening and Genetics Resource Center http://genes-r-us.uthscsa.edu/index.htm Organization of Teratology Information Services http://www.otispregnancy.org Save Babies Through Screening http://www.savebabies.org/ •

Prevention/Screening Accutane and Other Retinoids Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1168.asp Amniotic Fluid Abnormalities Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_4536.asp Common Concerns and Exposures Source: Center for the Evaluation of Risks to Human Reproduction http://cerhr.niehs.nih.gov/genpub/topics/ccae_index.html Folic Acid Frequently Asked Questions (FAQs) Source: National Center on Birth Defects and Developmental Disabilities http://www.cdc.gov/ncbddd/folicacid/folicfaqs.htm Food-Borne Risks in Pregnancy Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1152.asp Maternal Blood Screening Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1166.asp Newborn Screening Tests Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/298_834.asp Pregnancy and the Drug Dilemma Source: Food and Drug Administration http://www.fda.gov/fdac/features/2001/301_preg.html

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Thalidomide Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1172.asp Triple Screen Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/159_522.asp What You Can Do to Keep Germs from Harming You or Your Baby Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dbmd/gbs/PDFs/What%2520you%2520can%2520d o-English%25202000%2520for%2520pdf.pdf •

Research Birth Defects Research Source: National Center on Birth Defects and Developmental Disabilities http://www.cdc.gov/ncbddd/bd/bdres.htm Congenital Causes of Venous Thrombosis--Classification System Source: American College of Physicians http://www.annals.org/cgi/content/full/138/2/I-39 Fertility Treatments and Craniosynostosis, California, Georgia, and Iowa, 19931997 http://www.cdc.gov/ncbddd/factsheets/pediatrics/Pediatrics_fertilitycraniosyn.p df Maternal Obesity and Risk for Birth Defects http://www.cdc.gov/ncbddd/factsheets/pediatrics/Pediatrics_maternal_obesity.p df

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Statistics Birth Defects Become a Leading Cause of U.S. Infant Deaths Source: American College of Obstetricians and Gynecologists http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZF01KTKSC& sub_cat=543 FASTATS: Birth Defects Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/bdefects.htm Leading Categories of Birth Defects Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/aboutus/680_2164.asp

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.

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The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on birth defects. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Prevention of birth defects Source: San Diego, CA: San Diego- Imperial Counties Developmental Services. n.d. 4 pp. Contact: Available from James O. Cleveland, Ed.D., San Diego- Imperial Counties Developmental Services, 4355 Ruffin Road, Suite 205, San Diego, CA 92123. Telephone: (619) 576-2813 / fax: 619-576-2873. Summary: This booklet, available in English, Spanish, and Vietnamese, lists some factors associated with birth defects and a brief list of common birth defects. Also listed are tips to prevent birth defects, tests for identifying birth defects, and the advantages of genetic counseling. [Funded by the Maternal and Child Health Bureau].

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Association of Birth Defect Children (ABDC) Source: Orlando, FL: Association of Birth Defect Children, Inc. (ABDC). 199X. 2 p. Contact: Available from Association of Birth Defect Children, Inc. (ABDC). 827 Irma Street, Orlando, FL 32803. (407) 245-7035. PRICE: Single copy free. Summary: This brochure describes the Association of Birth Defect Children (ABDC), a national clearinghouse founded in 1982 to provide parents and professionals with information about birth defects and services for children with disabilities. The brochure describes the ABDC projects and services, including the National Birth Defects Registry; parent matching program; birth defect fact sheets; ABDC newsletters; teratogen information; and health resource reports. The brochure includes a membership application with which readers can join the ABDC.

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Cleft Lip, Palate and Craniofacial Birth Defects: The Multidisciplinary Treatment that is Reinforced by Smiles Source: Chapel Hill, NC: Cleft Palate Foundation. 199x. [2 p.]. Contact: Available from Cleft Palate Foundation, Inc. 104 South Estes Drive, Suite 204, Chapel Hill, NC 27514. (800) 242-5338 or (919) 933-9044. Fax (919) 933-9604. Website: www.cleft.com. PRICE: Single copy free. Summary: This brochure is designed to familiarize healthcare providers with the CleftLine service that is available from the Cleft Palate Foundation (CPF). The Foundation supports the concept of providing information and support to the parents as soon as possible following the birth of a child with cleft lip or cleft palate. The brochure includes a perforated Rolodex-type card with the CPF toll-free number (800-24-CLEFT). This CleftLine is available to everyone seeking information and referral for the treatment of cleft lip, cleft palate, and other craniofacial anomalies. Lists of cleft palate and craniofacial teams in a particular state or region and contacts for parent support groups will be provided by the CleftLine.

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What every family should know about preventing birth defects Source: Richmond, VA: Virginia Department of Health. 2000. 2 pp. Contact: Available from Dina Crowder, Marketing Support Solutions, 110 Vista Centre Drive, Forest, VA 24551. Telephone: (804) 385-1900 or (800) 474-3928 / fax: (804) 3854996 / e-mail: [email protected]. Available at no charge up to 500 copies per order; order by mail or fax. Summary: This brochure presents information about birth defects. The brochure addresses the definition of birth defects, presents some statistics, and offers information about prevention. Resources for additional information are given.

•

Maternal serum alpha-fetoprotein: A new test for the prenatal detection of open neural tube and certain other birth defects Source: Newark, NJ: University of Medicine and Dentistry of New Jersey. n.d. 4 pp. Contact: Available from Gisela Rodriquez, University of Medicine and Dentistry of New Jersey, Outreach Program, Department of Pediatrics, Division of Human Genetics, 185 South Orange Avenue, Newark, NJ 07103-27 57. Telephone: (201) 456-4598. Summary: This illustrated pamphlet answers questions the disorders for which alphafetoprotein analysis screens and explains the significance of elevated and low AFP levels. The pamphlet is available in French, Spanish, and English. [Funded by the Maternal and Child Health Bureau].

•

Facts about birth defects Source: San Diego, CA: San Diego Regional Center for the Developmentally Disabled. n.d. 12 pp. Contact: Available from James O. Cleveland, San Diego- Imperial Counties Developmental Services, 4355 Ruffin Road, Suite 205, San Diego, CA 92123. Telephone: (619) 576-2813 / fax: 619-576-2873. Summary: This pamphlet, available in Spanish and English, provides general facts about birth defects in a question-and-answer format. It tells what a birth defect is, the history of learning about birth defects, the frequency of birth defects, some simple genetics that describes the inheritance of these defects, some known environmental factors that cause defects, and the role of prenatal care. It also describes aspects of prenatal care, the different tests, several high risk factors, and other influences on pregnancy outcome. At the end, there is a birth defects prevention checklist of fourteen questions that may be helpful for a couple's initial genetic counseling visit. Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Birth Defects Source: March of Dimes Birth Defects Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3260

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Birth Defects and Pediatric Genetics Summary: This online site answers some important questions on birth defects and outlines the National Center for Environmental Health's prevention activities through its Birth Defects and Pediatric Genetics Source: National Center on Birth Defects and Developmental Disabilities http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=850

•

Decreasing the Chance of Birth Defects Summary: Of the 4 million infants born annually in the United States, about 3 to 5 percent are born with birth defects, according to the March of Dimes. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1409

•

FAQ - Why Folic Acid Is So Important Summary: The National Center for Environmental Health (NCEH) answers questions on the causes and prevention of the birth defects spina bifida and anencephaly. Discusses the dietary supplement foloic acid. Source: National Center for Environmental Health, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1227

•

Genetic and Rare Conditions: Support Groups & Information Page Summary: Professionals, educators, or individuals seeking information on genetic conditions or birth defects can use this directory to locate national and international organizations, or contact a genetic Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2861

•

Health Topic: Infants and Children Page - Centers for Disease Control and Prevention Summary: An index of health and safety topics that are specific to infants and children including childhood diseases, immunization, injuries, developmental disabilities, child abuse, birth defects and more. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=365

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•

healthfinder® just for you: Infants Summary: healthfinder®'s just for you: Infants section features topics such as birth defects, child care, and sudden infant death syndrome (SIDS). Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7015

•

healthfinder® just for you: Parents Summary: healthfinder®'s just for you: Parents sections features topics such as adoption, birth defects, and child care. Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7023

•

Preventing Neural Tube Birth Defects: A Prevention Model and Resource Guide Summary: This resource manual has been produced by the Centers for Disease Control and Prevention (CDC) to assist in the development and implementation of folic acid promotion/NTD prevention campaigns. Source: National Center for Environmental Health, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3898

•

The Folic Acid National Campaign Summary: The CDC, the March of Dimes, and the National Council on Folic Acid have organized the National Folic Acid Campaign to promote the use of folic acid to prevent the serious birth defects spina bifida Source: National Center on Birth Defects and Developmental Disabilities http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4470

•

What Is Fetal Alcohol Syndrome? Summary: Describes fetal alcohol syndrome (FAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). Source: National Organization on Fetal Alcohol Syndrome http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6958 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 birth defects. 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

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background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Birth Defects The following is a list of associations that provide information on and resources relating to birth defects: •

Association of Birth Defect Children, Inc Telephone: (407) 245-7035 Toll-free: (800) 313-2232 Fax: (407) 895-0824 Email: [email protected] Web Site: http://www.birthdefects.org Background: The Association of Birth Defect Children is a national not-for-profit organization that functions as a clearinghouse, providing parents and professionals with information about birth defects and services for children with disabilities. Founded in 1982, it sponsors the National Birth Defect Registry and a parent matching service. It also studies the links between drugs, radiation, alcohol, chemicals, lead, mercury, dioxin, and birth defects. The Association of Birth Defect Children operates with a staff and community volunteers under the guidance of a board of directors and two professional advisory boards. Newsletters and publications are supplied to parents, professionals, and interested organizations. Free questionnaires and information packets are available through the organization's toll-free Birth Defect Registry Hotline. Relevant area(s) of interest: Birth Defects

•

Birth Defect Research for Children, Inc Telephone: (407) 895-0802 Fax: (407) 895-0824 Email: [email protected]

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Web Site: http://www.birthdefects.org Background: Birth Defect Research for Children, Inc., (BDRC) formerly the Association of Birth Defect Children gives parents and expectant parents information about specific birth defects, their causes and treatments, support group referrals and parent-matching services. BDRC also provides information about environmental exposures that may be associated with birth defects. To study these exposures further, BDRC sponsors the National Birth Defect Registry, a research project designed to collect data on all kinds of birth defects and prenatal/preconceptual exposures of mothers and fathers. Relevant area(s) of interest: Birth Defects •

Birth Defects Foundation Telephone: 08700-707020 Toll-free: (800) 538-5390 Fax: 01543-468999 Email: [email protected] Web Site: http://www.birthdefects.co.uk Background: The Birth Defects Foundation (BDF) is a UK-registered charity whose mission is to improve child health, aid families, and create awareness of child-health challenges. BDF funds basic and clinical research into the causes, prevention and treatment of birth defects. It also operates a Here to Help Service, which is manned by qualified nurses who provide a professional and confidential service by offering support to those affected by, at risk of, or concerned about birth defects. BDF publishes information for families in free publications used in hospitals and elsewhere. Relevant area(s) of interest: Birth Defects

•

Cedars-Sinai Medical Genetics-Birth Defects Center Telephone: (310) 423-9914 Fax: (310) 423-9939 Web Site: http://www.cedars-sinai.edu/genetics Background: Cedars-Sinai's Medical Genetics-Birth Defects Center is a multidisciplinary outpatient center providing comprehensive services in the diagnosis, prevention and management of all forms of hereditary disorders and birth defects affecting fetuses, newborns, children, adolescents and adults. The Center also provides inpatient consultations. The Medical Genetics-Birth Defects Center conducts teaching programs and an active residency training program, which is largely funded by numerous groups from the National Institutes of Health (NIH) and other sources interested in the genetic basis of many diseases. Relevant area(s) of interest: Birth Defects

•

March of Dimes Birth Defects Foundation Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.marchofdimes.com

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Background: The March of Dimes Birth Defects Foundation is a national not-for-profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. The March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it also produces a wide variety of printed informational materials and videos. The Pregnancy and Newborn Health Education Center staffs trained health information specialists who provide researched information on pregnancy issues, complications and risks, newborn care, birth defects, genetic diseases and related topics as well as referrals to relevant organizations and support groups. Relevant area(s) of interest: Birth Defects •

National Birth Defects Center Telephone: (781) 466-9555 Fax: (781) 487-2361 Email: thegenesisfund.org Background: The National Birth Defects Center is a clinical facility developed to serve individuals with birth defects and their families nationwide. Based in Massachusetts, the National Birth Defects Center engages in patient and family education, gives appropriate referrals, and provides brochures to anyone affected by or interested in specific birth defects and disorders. Relevant area(s) of interest: Birth Defects

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

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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 “birth defects” (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 “birth defects”. 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 “birth defects” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “birth defects” (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/

•

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

•

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

26

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

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•

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

•

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/

•

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

•

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/

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

187

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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BIRTH DEFECTS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Aborigines: Native inhabitants or indigenous individuals of a country. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [NIH]

Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [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 and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids,

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androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]

Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH]

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Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [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-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast

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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] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthesiology: A specialty concerned with the study of anesthetics and anesthesia. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anophthalmia: Absence of an eye or eyes in the newborn due to failure of development of the optic cup or to disappearance of the eyes after partial development. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with 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] Antihypertensive: An agent that reduces high blood pressure. [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] Antivirals: Drugs used to treat infections caused by viruses. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Ascus: A membrane-enclosed sporesack of ascomycetes which usually contains eight ascospores. Is produced from an ascogenic hypha in which haploid nuclei, previously present as dikaryous, fuse to form a diploid nucleus. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH]

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Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bifida: A defect in development of the vertebral column in which there is a central

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deficiency of the vertebral lamina. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Birth Certificates: Official certifications by a physician recording the individual's birth date, place of birth, parentage and other required identifying data which are filed with the local registrar of vital statistics. [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] Blastoderm: A single layer of cells produced by cleavage of the fertilized ovum and forming the outer cells of the blastula. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up

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of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Butylated Hydroxytoluene: Antioxidant used in foods, cosmetics, petroleum products, etc. It may inhibit some neoplasms and facilitate others. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

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Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Abnormalities: Congenital structural abnormalities of the cardiovascular system. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] 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 Adhesion: Adherence of cells to surfaces or to other 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 Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing

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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 Movement: The movement of cells from one location to another. [NIH] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH]

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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] Child Care: Care of children in the home or institution. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliated cells: Epithelial cells with fine hair-like strands on their free borders. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [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.

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[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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Coliphages: Viruses whose host is Escherichia coli. [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] Colloidal: Of the nature of a colloid. [EU] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in

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the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] 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] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH]

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Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Sutures: A type of fibrous joint between bones of the head. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [NIH] Craniosynostoses: Premature closure of one or more sutures of the skull. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]

Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclopia: Elements of the two eyes fused into one median eye in the center of the forehead of a fetal monster. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types,

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including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dactinomycin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [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] Dermatoglyphics: The study of the patterns of ridges of the skin of the fingers, palms, toes, and soles. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process

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of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Ectopic Pregnancy: The pregnancy occurring elsewhere than in the cavity of the uterus. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromagnetic Fields: Fields representing the joint interplay of electric and magnetic forces. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the

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chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [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] 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] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH]

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Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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] 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]

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ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [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] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [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

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laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraocular: External to or outside of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [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] Fathers: Male parents, human or animal. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell 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

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be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrula: The embryo in the early stage following the blastula, characterized by morphogenetic cell movements, cell differentiation, and the formation of the three germ layers. [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]

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Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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 Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genetics, Population: The study of the genetic composition of populations and of the effects of factors such as selection, population size, mutation, migration, and genetic drift on the frequencies of various genotypes and phenotypes. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid

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with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Cones: Bulbous enlargement of the growing tip of nerve axons and dendrites. They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal

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condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hazardous Waste: Waste products which, upon release into the atmosphere, water or soil, cause health risks to humans or animals through skin contact, inhalation or ingestion. Hazardous waste sites which contain hazardous waste substances go here. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] 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]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterochromatin: The portion of chromosome material that remains condensed and is transcriptionally inactive during interphase. [NIH] Heterodimers: 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]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH]

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Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Holoprosencephaly: Anterior midline brain, cranial, and facial malformations resulting from the failure of the embryonic prosencephalon to undergo segmentation and cleavage. Alobar prosencephaly is the most severe form and features anophthalmia; cyclopia; severe mental retardation; cleft lip; cleft palate; seizures; and microcephaly. Semilobar holoprosencepaly is characterized by hypotelorism, microphthalmia, coloboma, nasal malformations, and variable degrees of mental retardation. Lobar holoprosencephaly is associated with mild (or absent) facial malformations and intellectual abilities that range from mild mental retardation to normal. Holoprosencephlay is associated with chromosome abnormalities. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeotic: Characterizes genes the mutations of which lead to inappropriate expressions of characteristics normally associated with another part of the organism (homeotic mutants). [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] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless,

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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] 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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH]

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Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] 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

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signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] 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] Instar: The form of an insect during a particular stadium, i. e. any post-egg stage initiated or terminated by ecdysis. There are larval, nymphal, pupal, and adult instars; any larval stadium. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU]

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Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] 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 Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [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] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH] Kinetic: Pertaining to or producing motion. [EU] Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [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

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membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligands: A RNA simulation method developed by the MIT. [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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Neoplasms: Tumors or cancer of the liver. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] 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] Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines it lacks central nervous system depressing effects such as drowsiness. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU]

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Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maternal Exposure: Exposure of the female parent, human or animal, 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 that may affect offspring. It includes pre-conception maternal exposure. [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] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH]

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MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] 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] Melanoblasts: Cell originating from the neural crest that differentiates into a melanocyte. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

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] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH]

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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] 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] Methylenetetrahydrofolate Dehydrogenase: Catalyzes the oxidation of methylenetetrahydrofolate to 5,10-methenyltetrahydrofolate. Includes EC 1.5.1.15 which uses NAD+. EC 1.5.1.5. [NIH] Methylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Motors: Protein based machines that are involved in or cause movement such as the rotary devices (flagellar motor and the F1 ATPase) or the devices whose movement is directed along cytoskeletal filaments (myosin, kinesin and dynein motor families). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures.

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Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] 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] Monogenic: A human disease caused by a mutation in a single gene. [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] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]

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Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatology: A subspecialty of pediatrics concerned with the newborn infant. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube

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defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [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] Neurotrophins: A nerve growth factor. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Notochord: The rod-shaped body, composed of cells derived from the mesoblast and defining the primitive axis of the embryo. In lower vertebrates, it persists throughout life as the main axial support of the body, but in higher vertebrates it is replaced by the vertebral column. [NIH] NSAIDs: Nonsteroidal anti-inflammatory drugs. A group of drugs that decrease fever,

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swelling, pain, and redness. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] 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] Nurse Anesthetists: Professional nurses who have completed postgraduate training in the administration of anesthetics and who function under the responsibility of the operating surgeon. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH]

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Optic cup: The white, cup-like area in the center of the optic disc. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orderly: A male hospital attendant. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthodontics: A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion). [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] 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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] 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]

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Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Paternal Exposure: Exposure of the male parent, human or animal, 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 that may affect offspring. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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 Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH]

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Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] 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] 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] 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] Phosphorylating: Attached to a phosphate group. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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,

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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]

Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pontine: A brain region involved in the detection and processing of taste. [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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the

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convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] 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] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [NIH] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] 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] Program Evaluation: Studies designed to assess the efficacy of programs. They may include the evaluation of cost-effectiveness, the extent to which objectives are met, or impact. [NIH]

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Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]

Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Prosthodontics: A dental specialty concerned with the restoration and maintenance of oral function by the replacement of missing teeth and structures by artificial devices or prostheses. [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 Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease

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characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychosexual Development: The stages of development of the psychological aspects of sexuality from birth to adulthood; i.e., oral, anal, genital, and latent periods. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] 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] Public Sector: The area of a nation's economy that is tax-supported and under government control. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is

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both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] 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] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]

of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly

Radon: A naturally radioactive element with atomic symbol Rn, atomic number 86, and atomic weight 222. It is a member of the noble gas family and released during the decay of radium and found in soil. There is a link between exposure to radon and lung cancer. [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] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU]

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Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rhythm Method: A contraceptive method whereby abstinence is practiced a few days before and after the estimated day of ovulation. [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] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room

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temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] 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] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Ratio: The number of males per 100 females. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as

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the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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]

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Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somite: One of the paired blocks of mesoderm present in each segment of the early embryo. [NIH]

Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the

Dictionary 239

ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superstitions: A belief or practice which lacks adequate basis for proof; an embodiment of fear of the unknown, magic, and ignorance. [NIH]

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Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Surgery, Plastic: The branch of surgery concerned with restoration, reconstruction, or improvement of defective, damaged, or missing structures. [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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Systemic: Affecting the entire body. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] 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]

Dictionary 241

Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH]

242 Birth Defects

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] 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] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for

Dictionary 243

nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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 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] 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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uteroglobin: A protein fraction of pregnant uterine fluid which can induce and regulate blastocystic development. Blastokinin is thought to be similar or identical to uteroglobin. Presence in uterine fluid regulated by progesterone. [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

244 Birth Defects

to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinyl Chloride: A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects,

Dictionary 245

particularly the occurrence of liver neoplasms. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] 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] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

246 Birth Defects

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] 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] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [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]

247

INDEX A Abdominal, 189, 204, 227, 242 Aberrant, 26, 28, 57, 189 Ablation, 19, 22, 83, 189 Aborigines, 65, 189 Abscess, 189, 236 Acceptor, 189, 227 Acetylcholine, 44, 189, 199, 225 Acitretin, 92, 150, 189 Acne, 147, 189 Acoustic, 138, 139, 189 Acrylonitrile, 189, 236 Actin, 17, 189, 223, 224 Action Potentials, 26, 189 Adenine, 189 Adenosine, 128, 189, 196, 218, 229 Adenosine Deaminase, 128, 189 Adenylate Cyclase, 189, 210 Adolescence, 189, 228 Adrenal Cortex, 189, 231 Adrenergic, 49, 190, 205, 207 Adrenergic Agents, 49, 190 Adverse Effect, 17, 147, 190, 237, 244 Aerosol, 190, 244 Afferent, 9, 190 Affinity, 41, 51, 190, 193, 237 Age of Onset, 190, 243 Ageing, 75, 190 Agenesis, 33, 190 Agonist, 190, 205, 225 Alertness, 190, 196 Alexia, 190, 205 Algorithms, 190, 195 Alimentary, 190, 217 Alkaline, 190, 191, 196, 234 Alkaloid, 190, 200, 225 Alleles, 8, 52, 54, 190, 214 Allergic Rhinitis, 191, 219 Alpha Particles, 191, 234 Alpha-fetoprotein, 124, 174, 191, 209 Alternative medicine, 145, 191 Alternative Splicing, 49, 191, 232 Amino Acid Sequence, 191, 192, 208 Amino Acids, 191, 228, 230, 232, 235, 239, 242 Ammonia, 189, 191 Amniotic Fluid, 171, 191, 211 Amphetamines, 191, 200

Anaesthesia, 191, 216 Anal, 28, 191, 207, 233 Analgesic, 191, 215 Analog, 191, 218 Analogous, 28, 191, 242 Anaphylatoxins, 191, 201 Anastomosis, 17, 192 Anemia, 192, 210 Anesthesia, 192 Anesthesiology, 4, 20, 84, 192 Anesthetics, 192, 194, 207, 226 Aneuploidy, 8, 38, 47, 132, 192 Angiogenesis, 17, 192, 220 Animal model, 5, 13, 24, 31, 47, 58, 192 Anomalies, 23, 24, 27, 40, 44, 55, 59, 85, 90, 92, 127, 133, 138, 147, 173, 192, 223, 227, 241 Anophthalmia, 45, 192, 214 Antagonism, 7, 192, 196 Antibacterial, 192, 238 Antibiotic, 115, 192, 228, 238, 241 Antibodies, 8, 192, 213, 214, 215, 216, 220, 229 Antibody, 30, 190, 192, 193, 200, 213, 214, 216, 220, 238 Anticoagulant, 192, 232 Anticonvulsant, 193, 244 Antigen, 34, 190, 192, 193, 200, 214, 215, 216, 217, 220 Antigen-Antibody Complex, 193, 200 Antihypertensive, 193, 210 Anti-inflammatory, 46, 116, 193, 215, 225 Antioxidant, 36, 193, 196 Antivirals, 35, 193 Anus, 191, 193, 196, 217 Aorta, 193, 244 Aponeurosis, 193, 210 Applicability, 51, 193 Aqueous, 193, 194, 203 Arginine, 191, 193, 225 Arterial, 193, 215, 232 Arteries, 193, 195, 202, 222, 233 Ascus, 32, 193 Aseptic, 193, 227, 239 Assay, 9, 13, 25, 33, 193 Astringents, 193, 221 Astrocytes, 193, 213 Asymptomatic, 34, 193

248 Birth Defects

Atrial, 59, 194 Atrium, 194, 241, 244 Auditory, 13, 194, 213, 244 Autonomic, 13, 189, 194, 225, 228, 237, 240 Autonomic Nervous System, 13, 194, 228, 237, 240 Avian, 55, 194 Axonal, 9, 18, 194, 246 Axons, 9, 18, 26, 53, 194, 212, 227 B Bacteria, 192, 193, 194, 207, 222, 229, 238, 242, 244 Bactericidal, 194, 208 Bacteriophage, 24, 194, 242 Barbiturate, 194, 241 Basal cell carcinoma, 21, 194 Basal cells, 194 Basal Ganglia, 194, 210 Base, 61, 189, 194, 196, 203, 218, 240 Basement Membrane, 22, 55, 194, 208, 218 Benign, 194, 210, 213, 224, 225 Bifida, 3, 194 Bilateral, 55, 147, 195, 242 Bile, 115, 195, 210, 214, 219, 239 Binding Sites, 13, 195 Biochemical, 8, 14, 15, 17, 21, 29, 35, 37, 38, 45, 59, 190, 195, 209, 211 Biological therapy, 195, 212 Biosynthesis, 195, 210 Biotechnology, 60, 61, 135, 145, 157, 195 Birth Certificates, 45, 195 Bladder, 195, 225, 243 Blastocyst, 195, 201, 206, 227, 229, 242 Blastoderm, 32, 195 Blood Coagulation, 195, 196, 241 Blood Glucose, 137, 195, 217 Blood pressure, 193, 195, 197, 215, 223, 233, 237 Blood vessel, 192, 195, 197, 198, 199, 207, 220, 221, 237, 239, 241, 244 Blot, 49, 195 Body Fluids, 195, 196, 237 Bone Marrow, 23, 127, 195, 215, 220, 223, 237 Bowel, 191, 196, 204, 225 Bowel Movement, 196, 204 Bradykinin, 196, 225 Branch, 6, 185, 196, 206, 220, 233, 238, 240, 241 Bronchi, 196, 207, 242 Butylated Hydroxytoluene, 36, 196 Bypass, 15, 34, 196

C Caffeine, 107, 196 Calcium, 49, 196, 200, 220, 237 Callus, 196, 206 Canonical, 53, 196 Capsid, 35, 196 Carbohydrates, 196, 198 Carbon Dioxide, 196, 229, 235 Carboxy, 54, 196 Carboxy-terminal, 54, 196 Carcinogen, 197, 243 Carcinogenic, 197, 217, 222, 226, 232, 239 Carcinoma, 197 Cardiac, 13, 25, 59, 60, 196, 197, 207, 208, 224, 239 Cardiogenic, 25, 197 Cardiovascular, 5, 24, 25, 59, 67, 83, 88, 197, 237 Cardiovascular Abnormalities, 5, 197 Cardiovascular disease, 88, 197 Cardiovascular System, 24, 197 Carotene, 197, 235 Case-Control Studies, 70, 71, 89, 90, 97, 197, 207 Caudal, 197, 204, 215, 230 Causal, 67, 106, 197, 207 Causality, 79, 197 Cause of Death, 50, 197 Cell Adhesion, 6, 9, 17, 197, 217 Cell Aggregation, 197, 227 Cell Communication, 7, 57, 197 Cell Cycle, 15, 22, 37, 56, 197, 202, 218, 244 Cell Differentiation, 18, 29, 55, 60, 197, 210, 237 Cell Division, 14, 18, 47, 194, 197, 198, 212, 217, 221, 222, 229, 232, 236 Cell Lineage, 22, 30, 59, 198 Cell membrane, 86, 107, 198, 203, 206, 210, 230, 237 Cell motility, 11, 17, 32, 53, 198 Cell Movement, 11, 198, 210 Cell Polarity, 11, 198 Cell proliferation, 14, 18, 22, 34, 53, 198, 237 Cell Size, 198, 209 Cell Survival, 198, 212 Cell Transplantation, 18, 33, 198 Cellulose, 196, 198, 229 Centromere, 9, 198 Cerebellar, 9, 198 Cerebellum, 198, 202

Index 249

Cerebral, 41, 158, 194, 198, 206, 207, 208, 209, 224, 240 Cerebral hemispheres, 194, 198, 240 Cerebral Palsy, 158, 198 Cerebrovascular, 197, 198 Cerebrum, 198, 202, 240 Character, 199, 203 Chemotactic Factors, 199, 201 Chemotherapy, 35, 199 Child Care, 176, 199 Chimera, 6, 199 Cholesterol, 195, 199, 202, 239 Cholinergic, 199, 225 Choroid, 199, 235 Chromatin, 199, 238 Chromosomal, 4, 19, 31, 52, 57, 92, 135, 169, 192, 199, 211, 223, 229, 240 Chromosome Abnormalities, 5, 58, 199, 214 Chromosome Segregation, 32, 36, 38, 47, 199 Chronic, 13, 14, 23, 125, 139, 199, 216, 218, 219, 232, 239 Chronic Disease, 14, 199 Ciliary, 44, 60, 199 Ciliated cells, 60, 199 Circulatory system, 17, 199 CIS, 39, 40, 48, 49, 57, 199, 235 Cleft Palate, 13, 26, 27, 29, 30, 33, 42, 47, 56, 64, 70, 136, 138, 139, 147, 169, 170, 173, 199, 214 Clinical Medicine, 199, 231 Clinical trial, 4, 43, 121, 122, 157, 199, 205, 223, 234 Clone, 13, 19, 38, 199 Cloning, 13, 30, 31, 195, 200, 217 Coca, 200 Cocaine, 71, 101, 200 Cofactor, 200, 232, 241 Cohort Studies, 29, 200, 207 Coliphages, 194, 200 Collagen, 18, 194, 200, 208, 209, 220, 230, 232 Colloidal, 200, 206 Coloboma, 101, 200, 214 Complement, 16, 191, 200, 201, 211, 217 Complementary and alternative medicine, 111, 117, 201 Complementary medicine, 111, 201 Computational Biology, 157, 201 Conception, 58, 67, 137, 201, 209, 220, 231, 239

Condoms, 137, 201 Cones, 53, 201, 235 Confounding, 13, 67, 106, 201 Connective Tissue, 16, 128, 129, 196, 200, 201, 210, 220, 221, 235 Connective Tissue Cells, 201 Consultation, 138, 201 Consumption, 24, 102, 125, 201, 203, 235 Contamination, 15, 94, 201 Contraception, 95, 137, 201 Contraceptive, 11, 58, 137, 147, 201, 235 Contraindications, ii, 201 Coordination, 41, 198, 201 Cornea, 201, 212 Corneum, 202, 207 Coronary, 197, 202, 222 Coronary heart disease, 197, 202 Coronary Thrombosis, 202, 222 Corpus, 202, 228, 231 Corpus Luteum, 202, 231 Cortex, 41, 42, 202, 208, 209, 224 Cortical, 41, 42, 44, 202, 236 Cortices, 202, 213 Corticosteroids, 65, 202 Cranial, 29, 46, 53, 54, 55, 128, 198, 202, 208, 213, 214, 224, 227, 228, 244 Cranial Sutures, 55, 202 Craniofacial Abnormalities, 30, 53, 146, 202 Craniosynostoses, 55, 202 Cribriform, 202, 226 Crossing-over, 202, 234 Cross-Sectional Studies, 202, 207 Cues, 9, 12, 14, 19, 59, 202 Curative, 202, 241 Cyclic, 16, 189, 196, 197, 202, 210, 212, 225 Cyclin, 56, 202 Cyclopia, 16, 202, 214 Cytokine, 47, 202, 241 Cytomegalovirus, 35, 203 Cytoplasm, 9, 198, 203, 207, 212, 223, 235, 240 Cytoskeleton, 8, 17, 203, 217, 222 Cytotoxic, 203, 237 D Dactinomycin, 62, 203 Databases, Bibliographic, 157, 203 De novo, 52, 203 Decidua, 203, 229 Defense Mechanisms, 203, 217 Degenerative, 37, 203 Delusions, 203, 233

250 Birth Defects

Dendrites, 9, 18, 203, 212, 225, 226 Dendritic, 9, 18, 203, 221 Density, 203, 209, 230 Dental Care, 3, 203 Dentists, 3, 4, 203 Deoxyguanosine, 71, 203 Depolarization, 203, 237 Dermatoglyphics, 128, 142, 203 Developing Countries, 14, 43, 50, 203 Diabetes Mellitus, 137, 204, 211 Diagnostic procedure, 146, 204 Diaphragm, 137, 204 Diarrhea, 204, 207 Diencephalon, 204, 215, 232, 240 Digestion, 190, 195, 196, 204, 219, 239, 244 Digestive system, 122, 204 Dihydrotestosterone, 204, 234 Dilatation, 204, 231, 244 Diploid, 32, 192, 193, 204, 223, 229, 242 Direct, iii, 6, 9, 20, 34, 36, 39, 41, 48, 51, 53, 57, 149, 197, 198, 199, 204, 205, 234, 240 Disease Susceptibility, 52, 204 Disinfectant, 204, 208 Disposition, 58, 63, 204 Dissection, 204, 242 Dissociation, 190, 204 Distal, 194, 204, 232 Diuresis, 196, 204 Dizziness, 139, 204 Dopamine, 200, 204, 229 Dorsal, 12, 42, 205, 224, 230, 238 Dorsum, 205, 210 Double-blinded, 43, 205 Drive, ii, vi, 36, 39, 105, 173, 174, 205 Drug Interactions, 150, 205 Drug Tolerance, 205, 241 Dynein, 205, 222 Dyslexia, 139, 205 Dystonia, 139, 205 E Ectoderm, 48, 53, 55, 205, 224 Ectopic, 34, 40, 41, 46, 53, 95, 205 Ectopic Pregnancy, 95, 205 Edema, 205, 231 Effector, 39, 53, 189, 200, 205 Efficacy, 205, 231 Elastin, 200, 205, 208 Elective, 81, 205 Electrolyte, 205, 230, 237 Electromagnetic Fields, 96, 205 Electrons, 193, 194, 205, 218, 227, 234 Electrophoresis, 20, 206

Electrophysiological, 49, 206 Electroporation, 41, 46, 206 Embryo Transfer, 206, 231 Embryogenesis, 7, 12, 13, 40, 43, 48, 53, 125, 206 Embryology, 33, 55, 126, 206 Encephalitis, 56, 206 Encephalitis, Viral, 206 Encephalocele, 206, 224 Encephalopathy, 65, 206 Endemic, 206, 238 Endocytosis, 54, 206 Endoderm, 5, 25, 53, 206 Endometrium, 22, 203, 207, 221, 242 Endothelial cell, 59, 207, 209, 241 Endothelium, 207, 225 Endothelium-derived, 207, 225 Endotoxins, 200, 207 Enhancer, 7, 207 Enterotoxins, 17, 207 Environmental Exposure, 21, 158, 159, 178, 207, 226 Environmental Health, 64, 67, 72, 73, 82, 92, 103, 112, 121, 156, 158, 175, 176, 207 Enzymatic, 196, 197, 200, 207, 214, 235 Enzyme, 25, 61, 189, 205, 207, 212, 230, 232, 234, 237, 241, 242, 245, 246 Epidemic, 3, 207, 238 Epidemiologic Studies, 73, 75, 207 Epidemiological, 44, 58, 65, 66, 85, 96, 207 Epidermal, 55, 207, 221 Epidermis, 55, 194, 202, 207, 214 Epinephrine, 190, 204, 207, 225, 243 Epithelial, 22, 33, 55, 60, 91, 199, 203, 207, 208, 218 Epithelial Cells, 22, 56, 207, 218 Epithelium, 19, 22, 33, 46, 55, 60, 91, 131, 194, 207 Erectile, 207, 228 ERV, 133, 160, 208 Erythrocytes, 192, 195, 208 Esophagus, 204, 208, 228, 239 Estrogen, 50, 91, 208 Ethanol, 6, 13, 24, 80, 208 Ethmoid, 208, 226 Etretinate, 189, 208 Eukaryotic Cells, 208, 216, 226, 227 Evoke, 208, 239 Excitability, 39, 49, 208 Excitation, 49, 191, 208, 209 Exhaustion, 192, 208 Exogenous, 75, 208, 243

Index 251

Exon, 191, 208 Expiratory, 208 Expiratory Reserve Volume, 208 Extracellular, 9, 51, 193, 201, 206, 208, 209, 217, 220, 237 Extracellular Matrix, 51, 201, 208, 209, 217, 220 Extracellular Matrix Proteins, 208, 220 Extracellular Space, 208, 209 Extraocular, 46, 209 F Facial, 20, 24, 26, 28, 29, 30, 43, 55, 128, 147, 170, 202, 209, 214, 237 Failure to Thrive, 24, 209 Family Planning, 157, 209 Fat, 195, 197, 202, 209, 219, 235, 237 Fathers, 10, 45, 178, 209 Fertilization in Vitro, 209, 231 Fetal Alcohol Syndrome, 6, 9, 23, 24, 124, 125, 132, 176, 209 Fetal Death, 81, 82, 94, 135, 147, 209 Fetal Development, 23, 24, 127, 129, 137, 209, 224 Fetoprotein, 126, 209 Fetus, 46, 58, 137, 191, 209, 229, 231, 238, 239, 243 Fibroblast Growth Factor, 22, 33, 51, 209 Fibroblasts, 6, 201, 209 Filtration, 19, 209 Fissure, 199, 200, 209 Flow Cytometry, 23, 56, 209 Fluorescence, 11, 209, 210 Fluorescent Dyes, 209, 210 Folate, 45, 76, 80, 88, 106, 109, 112, 210 Follow-Up Studies, 11, 210 Forskolin, 17, 210 G Gallbladder, 189, 204, 210 Ganglia, 189, 210, 224, 228, 240 Ganglion, 26, 44, 210, 224, 227 Gap Junctions, 210, 240 Gas, 191, 196, 208, 210, 215, 225, 234, 239, 244 Gastric, 116, 210, 214 Gastrin, 210, 214 Gastrointestinal, 196, 207, 208, 210, 237, 239 Gastrointestinal tract, 208, 210 Gastrula, 32, 210 Gene Expression, 7, 25, 28, 31, 33, 36, 39, 47, 54, 56, 57, 60, 211

Genetic Counseling, 14, 97, 130, 133, 173, 174, 211 Genetic Engineering, 195, 200, 211 Genetic Markers, 45, 211 Genetic Techniques, 8, 211 Genetics, Population, 14, 211 Genital, 27, 101, 170, 211, 233, 243 Genitourinary, 36, 211, 243 Genomics, 20, 37, 40, 211 Genotype, 51, 52, 70, 211, 229 Germ Cells, 211, 221, 226, 227, 238 Germ Layers, 205, 206, 210, 211 Gestation, 49, 50, 200, 211, 228, 229, 231, 238 Gestational, 35, 50, 137, 211 Gestational Age, 35, 50, 211 Gland, 189, 211, 220, 227, 229, 236, 239, 241 Glomeruli, 211, 226 Glucose, 137, 195, 198, 204, 211, 217, 236 Glucose Intolerance, 204, 211 Glutamate, 211, 229 Glutamic Acid, 210, 211, 232 Glycolysis, 80, 211 Glycoprotein, 58, 212, 218, 241, 243 Glycosaminoglycan, 51, 212 Gonadal, 212, 239 Gonadotropic, 22, 212 Gonads, 212 Governing Board, 212, 230 Grade, 142, 159, 212 Grading, 159, 212 Graft, 212, 214 Grafting, 212, 216 Granule, 9, 212, 235 Granulocytes, 212, 237, 245 Granulosa Cells, 23, 212 Grasses, 210, 212 Growth Cones, 53, 212 Growth factors, 22, 33, 51, 212 Guanylate Cyclase, 212, 225 H Habituation, 13, 212 Half-Life, 189, 212 Haploid, 32, 193, 212, 229 Haptens, 190, 213 Hazardous Waste, 73, 112, 213 Headache, 196, 213 Health Promotion, 4, 213 Hearing aid, 141, 213 Hearing Disorders, 141, 213 Heart attack, 197, 213

252 Birth Defects

Hematology, 50, 213 Hemorrhage, 213, 239 Hemostasis, 213, 217, 241 Heparan Sulfate Proteoglycan, 51, 213 Hepatic, 71, 213 Hereditary, 178, 213 Heredity, 131, 135, 210, 211, 213 Herpes, 35, 213 Herpes Zoster, 213 Heterochromatin, 38, 213 Heterodimers, 213, 217 Heterogeneity, 13, 51, 190, 213 Heterogenic, 213, 214 Heterogenous, 51, 213, 214 Heterozygotes, 5, 214 Histamine, 116, 192, 214, 219 Holoprosencephaly, 16, 45, 48, 54, 214 Homeobox, 33, 214 Homeotic, 57, 214 Homologous, 4, 37, 52, 190, 202, 214, 236, 240 Homozygotes, 5, 214 Hormonal, 22, 214 Hormone, 84, 202, 207, 210, 214, 217, 231, 237, 241 Horny layer, 207, 214 Host, 55, 56, 194, 200, 214, 215, 245 Human Development, 19, 156, 171, 214 Humoral, 23, 214 Humour, 214 Hybrid, 19, 24, 199, 214 Hybridization, 13, 30, 52, 214, 223 Hybridomas, 206, 214 Hydrogen, 189, 194, 196, 208, 214, 223, 225, 226, 227, 232, 246 Hydrolysis, 189, 215, 218, 229, 230, 232 Hydroxylysine, 200, 215 Hydroxyproline, 200, 215 Hypertension, 197, 213, 215, 231 Hypnotic, 194, 215, 241 Hypoglycemia, 137, 215 Hypoplasia, 59, 215 Hypothalamus, 194, 204, 215, 229 Hypothyroidism, 92, 124, 215 I Ibuprofen, 46, 215 Id, 108, 113, 169, 170, 177, 184, 186, 215 Idiopathic, 52, 215 Immune function, 56, 215 Immune response, 34, 193, 213, 215, 216, 239, 245 Immune Sera, 215

Immune system, 23, 36, 47, 195, 215, 216, 220, 243, 245 Immunization, 35, 175, 215, 231 Immunocompromised, 34, 56, 215 Immunodeficiency, 128, 158, 215, 216 Immunodeficiency syndrome, 158, 216 Immunofluorescence, 56, 216 Immunoglobulin, 192, 216 Immunohistochemistry, 13, 216 Immunologic, 199, 211, 215, 216 Immunology, 23, 47, 80, 190, 210, 216 Impairment, 216, 221, 233 Implantation, 23, 201, 216, 227 In situ, 6, 13, 19, 30, 31, 216 In Situ Hybridization, 6, 13, 19, 31, 216 In vitro, 17, 18, 24, 34, 35, 46, 48, 59, 71, 99, 121, 131, 197, 206, 216 In vivo, 5, 17, 18, 24, 27, 34, 44, 48, 53, 54, 59, 71, 216 Incision, 216, 218 Indicative, 125, 216, 244 Induction, 6, 37, 42, 216 Infancy, 30, 216 Infant Mortality, 69, 127, 135, 158, 179, 216 Infarction, 202, 216, 222 Infection, 23, 34, 158, 189, 193, 194, 195, 199, 203, 206, 215, 216, 220, 228, 239, 243, 245 Infertility, 23, 26, 32, 60, 83, 131, 145, 216 Inflammation, 189, 191, 193, 199, 206, 213, 216, 235 Ingestion, 213, 217, 230 Inhalation, 190, 213, 217, 230 Initiation, 37, 217, 242 Insecticides, 217, 228, 245 Insertional, 38, 217 Insight, 12, 19, 32, 34, 41, 48, 53, 217 Instar, 7, 217 Insulin, 137, 217, 243 Insulin-dependent diabetes mellitus, 217 Integrins, 17, 217 Intermittent, 217, 219 Internal Medicine, 213, 217 Interphase, 213, 217, 226 Intestinal, 197, 207, 217, 218 Intestines, 147, 189, 210, 217, 236 Intracellular, 16, 22, 36, 49, 53, 54, 56, 196, 198, 211, 216, 217, 225, 230, 237, 245 Intraocular, 200, 210, 217 Intraocular pressure, 210, 217 Intrinsic, 9, 190, 194, 217 Invasive, 53, 218

Index 253

Involuntary, 17, 218, 224 Ion Channels, 44, 193, 218, 240 Ion Exchange, 19, 198, 218 Ionizing, 191, 207, 218, 220, 228 Ions, 194, 204, 205, 215, 218, 230, 237 J Joint, 202, 205, 218 K Kb, 156, 218 Keratinocyte growth factor, 22, 218 Kidney Disease, 122, 137, 156, 218 Kinesin, 36, 38, 218, 222 Kinetic, 36, 38, 218 Kinetochores, 47, 218 L Labile, 200, 218 Lactation, 137, 138, 218 Laminin, 194, 209, 218 Lamivudine, 84, 218 Large Intestine, 204, 217, 218, 234, 237 Larynx, 218, 242, 244 Latent, 56, 219, 231, 233 Latent period, 219, 233 Lesion, 219 Lethal, 24, 60, 84, 194, 219 Lethargy, 215, 219 Leukocytes, 195, 199, 212, 219, 223, 243 Library Services, 184, 219 Life cycle, 190, 219 Life Expectancy, 137, 219 Ligands, 42, 54, 217, 219 Linkage, 11, 12, 15, 28, 31, 42, 51, 65, 100, 211, 219 Lip, 4, 27, 28, 30, 42, 78, 89, 132, 136, 138, 146, 147, 173, 214, 219 Lipid, 217, 219 Liver, 23, 26, 102, 147, 189, 191, 195, 203, 204, 210, 213, 219, 245 Liver cancer, 191, 219 Liver Neoplasms, 219, 245 Localization, 15, 58, 216, 219 Localized, 42, 58, 216, 218, 219, 229, 243 Locomotion, 39, 219, 229 Long-Term Care, 55, 219 Loop, 31, 219 Loratadine, 145, 219 Lumen, 17, 219 Lymph, 199, 207, 214, 220 Lymph node, 220 Lymphatic, 17, 207, 216, 220, 221, 237, 238, 241 Lymphatic system, 220, 237, 238, 241

Lymphocyte, 193, 220 Lymphoid, 35, 192, 202, 220 M Malformation, 29, 41, 128, 135, 220 Malignancy, 139, 220 Mandible, 26, 220 Manic, 220, 233 Manic-depressive psychosis, 220, 233 Manifest, 194, 220 Maternal Exposure, 65, 220 Matrix metalloproteinase, 22, 220 Medial, 22, 33, 41, 56, 208, 220 Mediate, 41, 47, 54, 205, 220 Mediator, 6, 220 Medical Staff, 205, 220 MEDLINE, 157, 221 Megaloblastic, 210, 221 Meiosis, 32, 36, 37, 38, 58, 199, 221, 240 Melanin, 221, 229, 243 Melanoblasts, 12, 221 Melanocytes, 221, 225 Membrane Glycoproteins, 221 Memory, 13, 39, 221 Meninges, 198, 221 Menstrual Cycle, 221, 231 Mental deficiency, 209, 221 Mental Disorders, 122, 221, 231, 233 Mental Health, iv, 4, 122, 156, 160, 221, 226, 231, 233 Mental Processes, 204, 221, 233 Mental Retardation, 8, 38, 52, 69, 93, 96, 139, 147, 158, 170, 214, 221 Mercury, 131, 177, 209, 221 Mesenchymal, 21, 22, 33, 55, 221 Mesoderm, 6, 16, 25, 40, 53, 55, 221, 238, 242 Meta-Analysis, 65, 103, 221 Metabolite, 189, 222 Metaphase, 218, 222 Metastasis, 53, 220, 222, 224 Methylenetetrahydrofolate Dehydrogenase, 61, 222 Methylnitrosourea, 35, 222 MI, 89, 101, 187, 222 Microbe, 222, 242 Microorganism, 200, 222, 228, 245 Microscopy, 9, 11, 15, 38, 53, 60, 194, 222, 226 Microtubules, 17, 218, 222 Migration, 12, 51, 53, 211, 222 Minority Groups, 69, 222 Miscarriage, 99, 114, 137, 147, 222

254 Birth Defects

Mitochondria, 222, 227 Mitosis, 36, 37, 38, 199, 222 Mitotic, 9, 37, 47, 218, 222 Modeling, 26, 222 Modification, 211, 222, 233, 246 Molecular Motors, 36, 222 Molecular Probes, 206, 222 Monitor, 159, 223, 226 Monocytes, 219, 223, 241 Monogenic, 29, 223 Monosomy, 192, 223 Morphogenesis, 6, 7, 8, 12, 17, 18, 25, 32, 39, 54, 55, 59, 128, 129, 209, 223 Morphological, 23, 30, 55, 190, 206, 221, 223 Morphology, 5, 9, 30, 39, 213, 223 Mosaicism, 84, 223 Motility, 11, 32, 36, 223 Mucinous, 210, 223 Mucins, 223, 236 Multicenter Studies, 50, 223 Multicenter study, 223 Muscle Contraction, 50, 223 Muscle Fibers, 18, 223, 224 Muscular Dystrophies, 18, 223 Mutagenesis, 7, 8, 29, 38, 223 Mutagenic, 222, 223 Mutagens, 130, 223 Mutate, 59, 224 Myocardium, 16, 25, 222, 224 Myosin, 8, 222, 223, 224 N NCI, 1, 122, 155, 199, 224 Necrosis, 216, 222, 224 Need, 3, 35, 43, 64, 106, 111, 123, 136, 137, 139, 141, 146, 147, 158, 170, 180, 220, 224, 241 Neocortex, 41, 224 Neonatal, 13, 23, 50, 60, 89, 107, 216, 224 Neonatology, 50, 224 Neoplasia, 21, 208, 224 Neoplasms, 196, 224 Nephropathy, 218, 224 Nerve Growth Factor, 224, 225 Nervous System, 11, 16, 19, 24, 26, 45, 48, 68, 128, 129, 189, 190, 191, 194, 196, 198, 200, 210, 211, 213, 219, 220, 224, 225, 227, 228, 229, 240, 244 Networks, 17, 21, 28, 39, 50, 224 Neural Crest, 12, 20, 53, 55, 59, 221, 224 Neural tube defects, 3, 11, 47, 61, 68, 71, 78, 94, 124, 209, 224

Neurologic, 139, 206, 225 Neurology, 6, 50, 65, 76, 83, 91, 112, 225 Neuroma, 139, 225 Neuromuscular, 37, 189, 225 Neuromuscular Junction, 189, 225 Neuronal, 15, 30, 36, 39, 44, 51, 212, 225 Neurons, 9, 19, 26, 39, 44, 200, 203, 210, 224, 225, 240 Neurotrophins, 19, 225 Neutrons, 191, 225, 234 Nevus, 170, 225 Nicotine, 44, 225 Nitrates, 103, 225 Nitric acid, 225 Nitric Oxide, 29, 225 Norepinephrine, 190, 204, 225 Notochord, 11, 18, 225 NSAIDs, 46, 116, 225 Nuclear, 35, 37, 60, 194, 206, 208, 210, 224, 226 Nuclei, 191, 193, 205, 211, 222, 225, 226, 227, 232 Nucleic acid, 196, 214, 216, 223, 226, 245, 246 Nucleic Acid Hybridization, 214, 226 Nucleolus, 54, 226, 235 Nucleus, 26, 38, 193, 199, 202, 203, 208, 221, 223, 225, 226, 232, 237, 239 Nurse Anesthetists, 84, 226 O Obstetrics, 10, 50, 92, 102, 107, 226 Occupational Exposure, 62, 65, 96, 100, 226 Occupational Health, 100, 226 Odds Ratio, 226, 234 Olfactory Bulb, 19, 226, 245 Oncogene, 47, 226 Oncogenic, 217, 226 Oocytes, 38, 226 Opsin, 226, 235 Optic cup, 192, 227 Optic Nerve, 227, 235 Orderly, 199, 227 Organ Culture, 22, 34, 227 Organ Transplantation, 35, 227 Organelles, 36, 203, 218, 221, 223, 227, 229 Orofacial, 27, 31, 45, 136, 227 Orthodontics, 4, 227 Otolaryngology, 4, 227 Outpatient, 178, 227 Ovarian Follicle, 23, 202, 212, 227 Ovary, 11, 22, 38, 202, 212, 227

Index 255

Ovulation, 212, 227, 235 Ovum, 195, 202, 203, 211, 219, 227, 231, 242, 245, 246 Ovum Implantation, 227, 242 Oxidation, 71, 189, 193, 222, 227 P Palate, 12, 22, 27, 28, 31, 33, 43, 55, 89, 132, 136, 138, 146, 147, 173, 199, 227 Palliative, 227, 241 Pancreas, 189, 204, 217, 227 Parasite, 56, 227 Particle, 228, 242, 245 Parturition, 226, 228 Paternal Exposure, 84, 228 Pathogen, 56, 228 Pathogenesis, 29, 31, 56, 80, 228 Patient Care Team, 146, 228 Patient Education, 173, 182, 184, 187, 228 Penicillin, 116, 192, 228 Penis, 27, 201, 228 Peptide, 19, 209, 228, 230, 232, 241 Perception, 130, 213, 228 Perinatal, 10, 50, 62, 66, 87, 93, 97, 132, 133, 134, 216, 228 Peripheral Nervous System, 44, 53, 228, 239 Pesticides, 65, 92, 99, 121, 159, 217, 228 Petroleum, 196, 228 Phallic, 27, 228 Pharmacists, 64, 106, 111, 147, 228 Pharmacokinetic, 9, 228 Pharmacologic, 192, 212, 228, 242 Pharynx, 5, 228, 244 Phenobarbital, 58, 229 Phenotype, 5, 13, 16, 19, 23, 29, 33, 38, 39, 52, 54, 229 Phenylalanine, 229, 243 Phospholipases, 229, 237 Phosphorus, 196, 229 Phosphorylating, 49, 229 Photoreceptors, 201, 229 Physical Examination, 211, 229 Physiologic, 190, 195, 209, 212, 221, 229, 234 Physiology, 23, 27, 35, 45, 49, 206, 213, 229 Pigment, 12, 221, 229 Pitch, 229, 245 Pituitary Gland, 209, 210, 229 Placenta, 58, 135, 229, 231, 233 Plants, 57, 190, 196, 200, 211, 223, 225, 229, 236, 242, 244 Plasma, 192, 198, 211, 213, 229

Plasma cells, 192, 229 Plasmid, 24, 229, 244 Plastids, 227, 229 Platelet Activation, 229, 237 Platelet Aggregation, 192, 210, 225, 230 Platelets, 225, 229, 230 Platinum, 219, 230 Poisoning, 221, 230 Polyethylene, 43, 230 Polymerase, 24, 230 Polymorphic, 45, 230 Polymorphism, 60, 61, 230 Polypeptide, 191, 196, 200, 214, 230, 246 Polysaccharide, 193, 198, 212, 230, 232 Pontine, 9, 230 Posterior, 7, 25, 33, 40, 41, 191, 198, 199, 205, 227, 230 Postnatal, 13, 24, 26, 88, 209, 230, 239 Postsynaptic, 18, 230, 237, 240 Potassium, 49, 109, 230 Potassium Channels, 49, 230 Potentiation, 230, 237 Practice Guidelines, 159, 230 Precipitating Factors, 197, 231 Preclinical, 67, 231 Precursor, 14, 18, 23, 204, 205, 207, 225, 229, 231, 243 Predisposition, 31, 78, 128, 231 Pre-Eclampsia, 11, 231 Pregnancy Outcome, 76, 100, 112, 174, 231 Pregnancy Tests, 147, 211, 231 Prenatal Care, 50, 174, 231 Prenatal Diagnosis, 22, 73, 78, 81, 130, 231 Presumptive, 25, 231 Presynaptic, 231, 240 Prevalence, 42, 66, 72, 81, 93, 97, 98, 226, 231 Primary Prevention, 72, 107, 231 Probe, 15, 231 Progeny, 14, 231 Progesterone, 50, 58, 231, 239, 243 Program Evaluation, 10, 231 Progression, 53, 56, 192, 232 Progressive, 197, 205, 212, 223, 224, 229, 232, 243 Projection, 203, 225, 226, 227, 232 Proline, 200, 215, 232 Promoter, 22, 34, 39, 232 Prophase, 32, 37, 226, 232, 240 Prosencephalon, 204, 214, 232, 240 Prospective study, 67, 232 Prosthesis, 43, 232

256 Birth Defects

Prosthodontics, 4, 43, 232 Protein C, 42, 48, 53, 191, 194, 232 Protein Isoforms, 191, 232 Protein S, 47, 135, 195, 232, 235, 241 Proteinuria, 231, 232 Proteoglycans, 194, 208, 232 Proteolytic, 54, 200, 232 Protons, 191, 215, 218, 232, 234 Proximal, 204, 231, 232, 236 Proxy, 57, 232 Psoriasis, 114, 189, 208, 232 Psychiatric, 27, 147, 221, 233 Psychiatry, 27, 139, 233 Psychology, 13, 73, 139, 204, 233 Psychosexual, 27, 233 Psychosexual Development, 27, 233 Psychosis, 148, 211, 233 Public Health, 14, 27, 50, 74, 75, 79, 87, 93, 96, 99, 101, 106, 108, 136, 158, 160, 233 Public Policy, 157, 233 Public Sector, 50, 233 Publishing, 60, 233 Puerperium, 226, 233 Pulmonary, 46, 195, 201, 233, 244 Pulmonary Artery, 195, 233, 244 Pulmonary hypertension, 46, 233 Pulse, 223, 233 Q Quality of Life, 43, 233 Quiescent, 15, 233 R Race, 50, 222, 233 Radiation, 19, 37, 65, 114, 177, 207, 209, 218, 220, 228, 234, 246 Radioactive, 212, 215, 216, 223, 226, 234 Radiography, 211, 234 Radium, 234 Radon, 15, 234 Randomized, 43, 205, 234 Reality Testing, 233, 234 Receptor, 6, 18, 20, 22, 26, 34, 41, 51, 54, 59, 193, 205, 219, 229, 234, 237 Recombinant, 24, 234, 244 Recombination, 5, 32, 37, 58, 211, 234 Rectum, 193, 196, 204, 210, 218, 234 Recurrence, 69, 97, 98, 220, 234 Reductase, 56, 234 Refer, 1, 200, 204, 213, 219, 225, 233, 234 Refraction, 234, 238 Regeneration, 53, 209, 234 Registries, 15, 29, 95, 158, 159, 234 Relative risk, 82, 234

Relaxant, 210, 234 Remission, 220, 234, 235 Reproduction Techniques, 231, 235 Respiration, 196, 222, 223, 235 Restoration, 232, 235, 240, 245 Retina, 26, 199, 201, 227, 235, 245 Retinal, 26, 46, 53, 227, 235 Retinoid, 25, 59, 189, 208, 235 Retinol, 110, 235 Reversion, 25, 235 Rheumatism, 215, 235 Rhythm Method, 137, 235 Ribose, 189, 235 Ribosome, 235, 242 Rigidity, 229, 235 Risk factor, 4, 11, 28, 58, 61, 63, 67, 82, 85, 92, 96, 174, 197, 207, 232, 234, 235 Rod, 17, 225, 235 Rodenticides, 228, 235 Rubber, 43, 189, 235 S Saliva, 34, 236 Salivary, 203, 204, 236 Salivary glands, 203, 204, 236 Saponins, 236, 239 Screening, 9, 11, 34, 42, 52, 83, 97, 124, 130, 137, 171, 199, 236 Secondary tumor, 222, 236 Secretion, 15, 116, 214, 215, 217, 218, 223, 236, 244 Secretory, 236, 240 Segmental, 18, 236 Segmentation, 214, 236 Segregation, 37, 38, 47, 199, 234, 236 Seizures, 214, 236 Seminiferous tubule, 236, 238 Septal, 59, 236 Sequencing, 19, 25, 30, 236 Serum, 124, 147, 174, 191, 200, 215, 236, 243 Sex Ratio, 62, 236 Sexually Transmitted Diseases, 35, 236 Shock, 236, 242 Side effect, 149, 190, 195, 236, 242, 246 Signal Transduction, 8, 26, 40, 53, 56, 237 Skeletal, 26, 29, 41, 44, 55, 147, 223, 237 Skeleton, 189, 218, 237 Skull, 146, 202, 206, 224, 237, 240 Small intestine, 214, 217, 237, 244 Smooth muscle, 49, 191, 196, 201, 210, 214, 237, 239 Social Environment, 233, 237

Index 257

Social Work, 139, 237 Sodium, 237, 244 Sodium Channels, 237, 244 Soft tissue, 195, 237 Solid tumor, 192, 237 Solitary Nucleus, 194, 237 Solvent, 208, 238 Somatic, 189, 206, 214, 221, 222, 228, 238, 244 Somatic cells, 221, 222, 238 Somite, 18, 40, 238 Spatial disorientation, 204, 238 Specialist, 146, 179, 238 Species, 5, 47, 55, 189, 198, 207, 213, 214, 221, 222, 227, 233, 238, 239, 242, 243, 245, 246 Specificity, 7, 39, 190, 238 Spectrum, 4, 23, 238 Speech Disorders, 139, 238 Sperm, 42, 95, 99, 199, 236, 238, 243 Spermatozoa, 81, 238 Spina bifida, 3, 8, 12, 48, 175, 176, 224, 238 Spinal cord, 54, 193, 198, 199, 210, 221, 224, 228, 238, 240 Spinal Nerves, 228, 238 Spinous, 207, 238 Spleen, 23, 203, 220, 238 Spontaneous Abortion, 5, 8, 37, 114, 137, 231, 238 Sporadic, 71, 84, 238 Stabilization, 16, 238 Stem Cells, 14, 23, 41, 48, 57, 238 Sterility, 216, 239 Sterilization, 95, 137, 239 Steroid, 58, 236, 239 Stillbirth, 50, 231, 239 Stimulant, 196, 214, 239 Stimulus, 13, 205, 208, 218, 239, 241 Stomach, 189, 204, 208, 210, 214, 217, 228, 237, 238, 239 Strand, 37, 65, 230, 239 Stress, 49, 137, 194, 231, 236, 239, 243 Stroke, 83, 122, 156, 169, 170, 171, 197, 239 Styrene, 236, 239 Subacute, 216, 239 Subclinical, 216, 236, 239 Subspecies, 238, 239 Substance P, 23, 222, 236, 239 Suction, 209, 239 Sulfur, 208, 218, 239 Superstitions, 88, 239

Supplementation, 22, 36, 47, 78, 81, 87, 88, 106, 107, 112, 240 Support group, 139, 140, 173, 178, 179, 240 Surgery, Plastic, 4, 240 Sympathetic Nervous System, 194, 240 Symptomatic, 34, 240 Synapses, 26, 226, 240 Synapsis, 240 Synaptic, 9, 39, 225, 237, 240 Synaptic Transmission, 225, 240 Synaptic Vesicles, 240 Systemic, 150, 193, 195, 207, 216, 240, 242 T Telencephalon, 41, 194, 232, 240 Telomere, 37, 240 Temporal, 5, 15, 22, 55, 98, 213, 240 Teratogen, 31, 36, 47, 133, 134, 173, 241 Teratogenesis, 7, 24, 36, 241 Teratogenic, 6, 13, 23, 24, 35, 47, 134, 208, 241 Teratogenicity, 147, 241 Terminalis, 240, 241 Testosterone, 234, 241 Tetracycline, 23, 116, 241 Thalidomide, 72, 90, 99, 132, 150, 172, 241 Therapeutics, 51, 150, 241 Thoracic, 204, 241, 245 Threshold, 208, 215, 241 Thrombin, 230, 232, 241 Thrombomodulin, 232, 241 Thrombophilia, 50, 241 Thrombosis, 172, 217, 232, 239, 241 Thymus, 215, 220, 241 Thyroid, 83, 87, 215, 241, 243 Thyrotropin, 215, 241 Tissue, 8, 11, 16, 18, 25, 29, 45, 46, 49, 51, 189, 192, 193, 194, 195, 199, 201, 205, 206, 207, 208, 209, 212, 215, 219, 220, 221, 223, 224, 225, 228, 229, 234, 235, 237, 239, 241, 242, 243, 245 Tolerance, 13, 211, 241 Tonicity, 205, 241 Topical, 193, 208, 241 Toxic, iv, 44, 126, 207, 212, 220, 225, 228, 239, 242, 246 Toxicity, 24, 129, 205, 221, 242, 244 Toxicology, 35, 72, 79, 80, 82, 87, 94, 99, 142, 158, 242 Toxins, 193, 206, 207, 216, 242 Trachea, 17, 196, 219, 228, 241, 242 Transcriptase, 218, 242, 246

258 Birth Defects

Transcription Factors, 7, 21, 25, 31, 39, 40, 57, 59, 60, 242 Transduction, 8, 36, 237, 242 Transfection, 7, 46, 195, 206, 242 Transfer Factor, 215, 242 Translating, 29, 242 Translation, 49, 242 Translational, 49, 242 Transmitter, 189, 193, 204, 218, 220, 225, 240, 242 Transplantation, 25, 127, 206, 215, 242 Trauma, 43, 213, 224, 242 Trees, 235, 242 Trisomy, 5, 38, 57, 192, 242 Trophoblast, 58, 195, 242 Truncal, 16, 242 Tryptophan, 200, 242 Tuberculosis, 201, 243 Tubulin, 222, 243 Tumor Necrosis Factor, 241, 243 Tumour, 210, 243 Type 2 diabetes, 137, 243 Tyrosine, 51, 204, 243 U Ultrasonography, 211, 243 Unconscious, 192, 203, 215, 243 Urethane, 47, 243 Urethra, 228, 243 Urinary, 170, 211, 243 Urine, 137, 147, 195, 204, 232, 243 Urogenital, 211, 243 Urologist, 27, 243 Urticaria, 219, 243 Uterine Contraction, 49, 243 Uteroglobin, 22, 243 Uterus, 22, 202, 203, 205, 207, 231, 243, 244 V Vaccine, 34, 243 Vacuoles, 206, 227, 244 Vagal, 12, 244 Vagina, 244 Vaginal, 95, 244 Vagus Nerve, 237, 242, 244 Valproic Acid, 47, 116, 244 Vascular, 17, 29, 55, 101, 139, 199, 207, 216, 225, 227, 229, 243, 244 Vasodilators, 225, 244

VE, 66, 101, 244 Vector, 217, 242, 244 Vegetative, 32, 57, 244 Vein, 7, 226, 244 Venous, 45, 172, 232, 244 Ventral, 16, 215, 238, 244 Ventricle, 16, 215, 233, 244 Ventricular, 59, 244 Vertebrae, 238, 244 Vertebral, 194, 225, 238, 244 Vesicular, 212, 213, 244 Veterinary Medicine, 47, 157, 244 Villi, 244 Villous, 103, 244 Vinyl Chloride, 74, 244 Viral, 35, 49, 196, 206, 226, 242, 245, 246 Virulence, 57, 242, 245 Virus, 34, 35, 158, 194, 196, 207, 211, 242, 245 Virus Replication, 35, 245 Visceral, 194, 244, 245 Visceral Afferents, 194, 244, 245 Vital Statistics, 195, 245 Vitamin A, 59, 102, 137, 235, 245 Vitreous Body, 235, 245 Vitro, 25, 245 Vivo, 24, 44, 53, 245 Voice Disorders, 139, 245 Volition, 218, 245 Vomeronasal Organ, 226, 245 W Weight Gain, 137, 209, 245 White blood cell, 192, 219, 220, 229, 245 Windpipe, 228, 241, 245 Womb, 243, 245 Wound Healing, 209, 217, 220, 245 X Xenobiotics, 58, 245 Xenograft, 192, 246 X-ray, 210, 226, 246 Y Yeasts, 229, 246 Z Zalcitabine, 218, 246 Zygote, 201, 223, 246 Zymogen, 232, 246

Index 259

260 Birth Defects

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