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

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Williams Syndrome: 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: 0-597-84686-3 1. Williams Syndrome-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 Williams syndrome. 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 WILLIAMS SYNDROME .............................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Williams Syndrome....................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 33 The National Library of Medicine: PubMed ................................................................................ 34 CHAPTER 2. NUTRITION AND WILLIAMS SYNDROME .................................................................... 77 Overview...................................................................................................................................... 77 Finding Nutrition Studies on Williams Syndrome ..................................................................... 77 Federal Resources on Nutrition ................................................................................................... 78 Additional Web Resources ........................................................................................................... 79 CHAPTER 3. ALTERNATIVE MEDICINE AND WILLIAMS SYNDROME.............................................. 81 Overview...................................................................................................................................... 81 National Center for Complementary and Alternative Medicine.................................................. 81 Additional Web Resources ........................................................................................................... 82 General References ....................................................................................................................... 83 CHAPTER 4. DISSERTATIONS ON WILLIAMS SYNDROME................................................................ 85 Overview...................................................................................................................................... 85 Dissertations on Williams Syndrome .......................................................................................... 85 Keeping Current .......................................................................................................................... 86 CHAPTER 5. BOOKS ON WILLIAMS SYNDROME .............................................................................. 87 Overview...................................................................................................................................... 87 Book Summaries: Federal Agencies.............................................................................................. 87 Book Summaries: Online Booksellers........................................................................................... 88 Chapters on Williams Syndrome ................................................................................................. 89 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 93 Overview...................................................................................................................................... 93 NIH Guidelines............................................................................................................................ 93 NIH Databases............................................................................................................................. 95 Other Commercial Databases....................................................................................................... 97 The Genome Project and Williams Syndrome ............................................................................. 97 APPENDIX B. PATIENT RESOURCES ............................................................................................... 103 Overview.................................................................................................................................... 103 Patient Guideline Sources.......................................................................................................... 103 Associations and Williams Syndrome........................................................................................ 106 Finding Associations.................................................................................................................. 107 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109 Overview.................................................................................................................................... 109 Preparation................................................................................................................................. 109 Finding a Local Medical Library................................................................................................ 109 Medical Libraries in the U.S. and Canada ................................................................................. 109 ONLINE GLOSSARIES................................................................................................................ 115 Online Dictionary Directories ................................................................................................... 116 WILLIAMS SYNDROME DICTIONARY................................................................................. 119 INDEX .............................................................................................................................................. 155

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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 Williams syndrome 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 Williams syndrome, 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 Williams syndrome, 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 Williams syndrome. 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 Williams syndrome, 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 Williams syndrome. The Editors

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

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CHAPTER 1. STUDIES ON WILLIAMS SYNDROME Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Williams syndrome.

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

Increased Prevalence of Urinary Symptoms and Voiding Dysfunction in Williams Syndrome Source: Journal of Pediatrics. 129(3): 466-469. September 1996. Summary: This article reports on an increased prevalence of urinary symptoms and voiding dysfunction in a population of patients with Williams syndrome, a genetic disorder characterized by a specific dysmorphic face and habitus, postnatal growth deceleration, mild to moderate psychomotor retardation, a characteristic personality, and multiple organ dysfunction. Thirteen of 41 patients (32 percent) with Williams syndrome in a multidisciplinary clinic were noted to have genitourinary symptoms. The predominant features were increased urinary frequency and daytime wetting. Four patients had bladder diverticula and uninhibited detrusor contractions as demonstrated

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on urodynamic studies. The authors speculate that there may be an association between increased detrusor pressure, an abnormal bladder matrix, and the presence of diverticula. Early detection of urinary dysfunction through clinical symptoms and appropriate urodynamic studies, with institution of bladder training and anticholinergic medication, can improve patients' voiding patterns, both medically and socially. 1 table. 9 references. (AA-M). •

Williams Syndrome: Report of a Case Source: Oral Surgery, Oral Medicine, Oral Pathology. 74(6): 756-759. December 1992. Summary: Williams syndrome is a rare anamoly, consisting of idiopathic hypercalcemia that is normally accompanied by aortic stenosis, moderate mental retardation, and a characteristic elfin face. This disease can eventually be detected in the dental or orthodontic clinic, because people with this syndrome have severe dental abnormalities. In this article, a unique case of this type is reported. The authors note that, although the genetic bases of the disease are not clear, an underlying disorder may exist, implying a dominant autosomal inheritance with a great variety of forms. 7 figures. 14 references. (AA-M).

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

Project Title: A STIMULUS CONTROL ANALYSIS OF ATTENDING Principal Investigator & Institution: Serna, Richard W.; Associate Professor; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: In typically-developing children, initially slow, one-at-a-time word learning is followed by an apparent "explosion" in their lexicon. One estimate suggests that children are learning up to nine new words a day through slow and deliberate effort (e.g., McLean, 1993). Yet word learning is a foundational component of human

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

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development, necessary for advanced linguistic functions (e.g. syntactic operations) and contributing to complex representation skills (for instance, categorization; Bowerman, 1988). Yet word learning is a foundational component of human development, necessary for advanced linguistic; Bowerman, 1998). To the extent that a cognitive disability interferes with cord learning, progress in these domains will be correspondingly limited. It is therefore essential to explore in detail the nature of lexical impairments in mental retardation. The existence of difficulties in lexical acquisition among individuals with severe mental retardation raises important questions. When rapid vocabulary expansion occurs, what linguistic/cognitive processes support that learning? When it does not occur, what skills are deficient or absent? A phenomenon called fast mapping may be of greatest potential relevance for rapid vocabulary expansion. Fast mapping refers to a "quick, initial, partial understanding of a 'new' word's meaning" derived from the context of word use )Rice, 1989, p.152). Fast mapping has been argued to facilitate the vocabulary expansion. This proposed role has received empirical confirmation in typical youngsters and children with Down Syndrome )Mervis & Bertrand, 1994, 1995). Yet evidence from children with atypical cognition/language has recently challenged the universality of this relation. My own studies (Wilkinson & Green, 1997) have added to preliminary evidence of selective deficits in fast mapping among individuals with severe mental retardation, Williams Syndrome, or specific language purpose of vocabulary expansion. These recent findings oblige a more systematic analysis of the precise role of the principle in learning outcomes in mental retardation. Is fast mapping at risk in individuals with severe mental retardation, potentially limiting their vocabulary expansion? I propose a five-year study of vocabulary expansion and delay, focusing specifically on rapid expansion of an extant, but limited, vocabulary. This study will implement methods developed by the applicant (Wilkinson & Green, 199) that for the first time enable systematic analysis of unresolved questions of lexical expansion in severe mental retardation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF PHD-DOMAIN PROTEINS REQUIRED FOR MEIOSIS Principal Investigator & Institution: Makaroff, Christopher A.; Professor of Biochemistry; Chemistry and Biochemistry; Miami University Oxford 500 E High St Oxford, Oh 45056 Timing: Fiscal Year 2002; Project Start 01-JUN-1997; Project End 30-JUN-2004 Summary: (provided by applicant): Meiosis represents a highly ordered series of events that results in the production of haploid gametes; it plays a central role in the reproduction of essentially all diploid organisms. As an experimental system, meiosis provides a valuable system to study many aspects of cellular function, including changes in chromatin conformation, recombination, nuclear and cellular division, and cell cycle control mechanisms. Through the analysis of the y9287 knockout mutation of Arabidopsis, which is defective in meiotic cell cycle control, a PHD domain containing protein has been identified. The phenotype of the y9287 mutation and the presence of nuclear-localization signals and the PHD domain suggest that Y9287 may participate in controlling meiotic gene expression or chromatin remodeling during meiosis. Experiments outlined in this proposal are designed to investigate these possibilities by determining the expression and localization patterns of Y9287 and by isolating proteins that interact with Y9287. In addition, preliminary experiments to isolate and characterize mutations in three additional Y9287-like PHD domain containing proteins are described to investigate their functions and determine it one or more are required for other aspects of meiosis. Information obtained from the studies outlined here will contribute

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significantly to our understanding of a number of areas, including (1) regulation of the meiotic cell cycle, (2) PHD-domain containing proteins and their role(s) in meiosis and (3) cell cycle control processes in general. Results from these experiments should also have significant health relevance. The process of meiosis lies at the heart of human reproduction. Given the numerous common themes observed between meiosis in different species, information obtained from this work should provide valuable insight into vertebrate systems. Furthermore, understanding the cell cycle and its control is critical to numerous different aspects of human health. Proper control of the cell cycle is responsible for cell growth and differentiation. Alterations in the cell cycle, specifically loss of control, are responsible for countless diseases. Finally, PHD-domain containing proteins have been associated with several diseases, including, Williams syndrome, head and neck squamous cell carcinomas, myeloid leukemia and autoimmune polyglandular syndrome type 1. Therefore, our studies will provide significant new insights into events associated with the meiotic cell cycle and the role(s) of PHD domain proteins, which should be applicable to numerous different systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUDITORY MEMORY PROCESSING IN WILLIAMS SYNDROME Principal Investigator & Institution: Marler, Jeffrey A.; Audiology and Speech Sciences; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): This project investigates the sensory and memory underpinnings of language processing in individuals with Williams syndrome (WS) and Down's syndrome (DS). Both syndromes are genetically-based neurodevelopmental disorders characterized by an uneven profile of language strengths and weaknesses. In the presence of mild-to-moderate mental retardation, individuals with WS show relative strengths in phonology, verbal short-term memory, and expressive vocabulary. In contrast, individuals with DS show relatively weak phonological abilities, poor verbal short-term memory, and diminished expressive vocabulary. In spite of minimal empirical support, current theories about language function in WS are frequently grounded upon an assumption of relative strengths in auditory processing. First, behavioral auditory measurements are examined including air conduction, tympanometry, otoacoustic emissions, simultaneous and backward masking. These measures are then compared with both (a) physiological responses indexing early auditory memory and (b) phonological analyses indexing early language processing. The inverse pattern of strengths and weaknesses in these two clinical populations provides an opportunity to: (1) empirically examine auditory sensitivity in individuals with WS, (2) empirically test the hypothesis that short-term auditory processing is particularly robust in individuals with WS, and (3) test a current hypothesis that there is a strong correlation between auditory processing, auditory memory, and phonological processing in two groups with confirmed genetic disorders. Important clinical applications are to investigate the possibility of higher-than-expected instances of hearing loss in WS and to identify auditory interactions with language function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS Principal Investigator & Institution: Merchant, Fatima; Lead Research Engineer; Advanced Digital Imaging Research, Llc 2450 S Shore Blvd, Ste 305 League City, Tx 775732997

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Timing: Fiscal Year 2004; Project Start 01-APR-2000; Project End 19-MAR-2006 Summary: (provided by applicant): This project will further develop automated instrumentation and image analysis techniques to detect gene duplications or deletions in interphase FISH, which are difficult to detect by routine cytogenetics. There is a growing list of genetic disorders that result from chromosomal anomalies, related to either duplications or deletions. These include: (1) neuropathies; Charcot-Marie-Tooth Disease (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP), (2) neurological disorders; Pelizaeus-Merzbacher Disease (PMD) and X-Linked Spastic Paraplegia (SPG2), (3) muscular wasting disorders; Duchene (DMD) and Becker Muscular Dystrophy (BMD), (4) contiguous-gene syndromes; Smith-Magenis Syndrome (SMS). Our approach is to use readily available DNA probes, followed by automated genetic screening to detect duplications/deletions. We will develop an imaging system for the automated identification of interphase cells, and use sophisticated image analysis for high-resolution detection and separation of microscopic rearrangements. In the Phase I project we evaluated the feasibility of newly developed imaging algorithms, for effectively and precisely identifying the separation of FISH dot duplicates. Algorithms were developed for automatically (1) segmenting dots, (2) computing the integrated fluorescence intensity of dots, (3) determining the separation distance, and (4) classifying duplicates and single dots. In Phase II we will incorporate the newly developed imaging algorithms into our automated imaging system, and test the prototype clinically. We will also develop and implement three-dimensional modeling techniques to obtain an unbiased estimate of the spatial distance between duplicated genes. Phase III will commercialize the instrument. Computer automation will make genetic screening practical on a large scale by reducing costs and relieving humans of tedious duties. This approach will be most valuable to medical genetics, particularly for screening CMT1A/HNPP, PMD/SPG2, DMD/BMD, and SMS. Duplications have also been identified for the Prader-Willi /Angelman syndrome region that result in autism. Duplications, such as for 22ql 1.2 and 17pl 1.2 have been described and result in a rather mild phenotype. But duplications of the Williams syndrome region have not been described and thus, the phenotype is unknown. The ability to screen patients for duplications by interphase FISH analysis will likely identify a large number of individuals that would benefit from medical intervention. It may uncover syndromes that previously had no identifiable etiology. This will provide a screening test and eventually a diagnostic test for those individuals with perhaps mild phenotypes, such as learning disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BAP135 IN THE CENTRAL NERVOUS SYSTEM Principal Investigator & Institution: Danoff, Sonye K.; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (Applicant's Abstract): This application outlines a training program to be carried out under the mentorship of Dr. Stephen Desiderio in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine. The applicant's goals are to study the role of a transcription factor, BAP135, in normal neuronal function, as well as to evaluate this gene as a candidate for the neurocognitive phenotype of Williams Syndrome. The training program has been designed to gain expertise in the fields of molecular biology and transcriptional regulation. BAP135 is a recently described transcription factor which appears to define a new family that also includes WBSCR11. BAP135 mRNA is expressed in multiple tissues in mouse, but is

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most abundant in regions of the central nervous system. Expression of BAP135 is highest during the development of synaptic connections and remains high in areas of ongoing synaptic plasticity. The pattern of BAP135 expression is of further interest as the gene for BAP135 maps to the region of chromosome 7 commonly deleted in the genetic disorder, Williams Syndrome. This syndrome includes a characteristic neurocognitive defect which might be explained by deletion of a transcription factor such as BAP135. Studies are proposed to gain an understanding of how BAP135 functions as a transcriptional activator in neurons. As part of Specific Aim 1, the cellular and subcellular localization of BAP135 protein with development will be established. This will also address the patterns of expression of the four isoforms of BAP135 known to exist. Several aspects of the induction of BAP135 transcriptional activation will be addressed in Specific Aim 2. Both DNA binding of BAP135 and transactivation of reporter constructs in neurons will be evaluated and the effect of pathways involved in synaptic plasticity on these functions will be addressed. Specific Aim 3 focuses on the pathway downstream of BAP135 in neurons. Genes modulated by BAP135 activity will be investigated using DNA expression arrays. Finally, in Specific Aim 4, lymphoblast lines from patients with Williams Syndrome will be examined for deletions and mutations in the BAP135 locus. Mutations identified will be evaluated for effects on DNA binding and transactivation by BAP135 in neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL LINEAGE MAGNETIC RESONANCE IMAGING Principal Investigator & Institution: Jacobs, Russell E.; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002 Summary: Quantitative volumetric studies of brain morphological changes between childhood, adolescence, and you adulthood have yielded interesting results. Past neurodevelopmental studies have, however, been limited by the technology available for magnetic resonance image (MRI) acquisition, image analysis, and ultimately computering power to best exploit imaging data. The methods proposed for this study of normal brain maturation will include very high resolution structural images, tissue segmentation, brain surface renderings for aid in detailed cortical anatomical segmentation, and surface and volume (voxel based) modeling spatial localization techniques. With these relatively sophisticated methods, questions abut the etiology of maturational changes in the brain (e.g., myelination vs. Synaptic pruning) may be further examined Perhaps more importantly, assessing the spatial anatomical location of these maturational changes will be possible. Specific Aims a) To spatially localize structural maturational changes in the developing human brain b) Quantify the statistical significance of localized changes in hypothesized regions of greatest change relative to regions predicted to show little age-related structural change. Williams syndrome is a rare metabolic disorder labeled in 1961 by the British cardiologist J.C. P. Williams. who described a syndrome which includes a specific heart defect. mental retardation, and a peculiar facial appearance. Williams subjects also exhibit a unique fractionation of higher cortical functioning. specifically. selective preservation of complex syntax in the face of marked and severe cognitive deficits. While it is widely known that specific language deficits can exist without any accompanying cognitive deficit, the opposite pattern in which linguistic abilities are spared despite overall cognitive deficits is rare. It seems likely that the marked and specific deficits in behavioral development, and resultant neuropsychological profile in Williams patients result from unique patterns of aberrant brain development. 1. To understand the brain

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morphometric differences between Williams Syndrome and developmentally normal children using a high resolution imaging protocol. 2). Use morphometric findings to analyze factors which may account for the distinctive behavioral profiles found in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE-BRAIN PHENOTYPING OF ATYPICAL CHINESE CHILDREN Principal Investigator & Institution: Karmiloff-Smith, Annette; U of L University College London University College London London, Timing: Fiscal Year 2003; Project Start 28-SEP-2003; Project End 28-FEB-2005 Summary: (provided by applicant): The present proposal describes a series of planning activities to develop an international collaborative program of research on cognitive and brain phenotypes of mentally retarded Chinese children with genetic disorders. Specifically, an international team of medical, psychological, genetic, and computational researchers from P.R. China, the United Kingdom, the United States, and Canada will collaborate to study Chinese children with Fragile-X syndrome (FXS), Williams syndrome (WS), and Down syndrome (DS). The specific aims of the present research planning proposal are:(1) To assess the existing research infrastructure at the Chinese institution (Zhejiang University) for conducting the proposed research activities, (2) To enhance the research capacities of our Chinese research team through workshops and short-term training; (3) To conduct pilot studies that (a) test the feasibility of a computer-assisted 3D photography-based system for identifying a large population of mentally retarded children whose facial dysmorphology may suggest FXS, WS or DS and verify such identifications by genetic tests, (b) translate, adapt, and pilot-test procedures developed by the researchers in UK, US, and Canada to assess children with genetic disorders in terms of their abilities in the areas of language, executive function, and faces and visual-spatial information processing, and compare the Chinese children's cognitive profiles with the existing profiles of affected Western children; (c) use eventrelated potential techniques to examine the neuro-physiological correlates of a small group of the Chinese children with WS, FXS, and DS when they process language and face-spatial information, and compare the results with those obtained with the existing samples of affected Western children. Based on the outcome of 1,2, and 3, the international interdisciplinary team will develop a R01 research proposal that will systematically examine cognitive and brain functions or dysfunctions of Chinese children with Williams, Fragile-X, and Down syndromes from infancy to middle childhood. Our long-term goal is to chart the developmental trajectories of cognitive and brain development in children with genetic disorders, to understand the interaction between genetic abnormality and neuro-cognitive development in different sociocultural contexts, and to provide information for the creation of syndrome-specific and, if necessary, culture-specific intervention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--DIAGNOSTIC Principal Investigator & Institution: Trauner, Doris A.; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: The Diagnostic Medical/Behavioral Core will provide a framework for the identification and neurobehavioral screening evaluation of subjects entering into the

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individual projects. Before the state-of-the-art experimental procedures outlined in Core C and in the Projects can be applied to the study populations, it is crucial to determine whether individual children meet the neurologic and behavioral criteria for the group to which they are assigned. In addition, the Core neurologic and behavioral information provides a framework in which to better understand the significance of the experimental behavioral data. The major responsibilities of the Neurobehavioral Core B are: 1. Identification and induction of experimental and control subjects. 2. Screening of subjects for selection criteria as defined for each research project. 3. Administration and analysis of medical and behavioral questionnaires and medical/neurologic examinations. 4. Administration and scoring of a standardized behavioral test battery to all experimental and control subjects. 5. Tracking of all subjects from entry to completion of testing. 6. Acquisition of MRI sans when appropriate, with clinical interpretations performed by a clinical neuroradiologist. 7. Collaboration with Project Investigators to relate these diagnostic findings to the experimental findings obtained in the Project studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--LANGUAGE AND COGNITION Principal Investigator & Institution: Reilly, Judy S.; Professor; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: The primary function of Core C is to chart the developmental trajectories through adolescence of language, discourse, attention, spatial cognition, memory and executive function in both normally developing and experimental populations. The Core organization allows us to maximize the efficiency of testing and ensure the smooth flow of information regarding children's testing between the Projects and Cores. It also serves to enhance the consistency, reliability and validity of data collection across Center populations. Core C will have primary responsibility for testing and tracking all normally developing subjects. The experimental populations are those identified with the Population Projects, and include children with early and late brain damage, Language Impairment, Williams Syndrome, and Down Syndrome, and Down Syndrome. These will be tested in close collaboration with Core C on two sub-batteries: A) Longitudinal, off-line: Language, Discourse, Spatial Cognition, Memory, Executive Function; B) Cross-sectional, on-line: Language, Attention and Spatial Cognition. The first sub-battery includes measures to assess later language development, specifically metalinguistic and discourse abilities. By assessing linguistic performance in isolation and in discourse, we address issues of linguistic knowledge versus performance. Using the CHILDES system, Core C will transcribe and code all elicited spoken and written language data. The Attention and Spatial Cognition, Memory and Executive Function Battery includes measures to assess various levels of non-linguistic processing: visual and auditory attention; hemispatial neglect, spatial cognition, verbal and spatial memory, and executive function. These data will permit us to identify association and dissociations within and across the domains of linguistic and non- linguistic cognition. The on-line tasks of Testing Battery B are directly yoked to the neuro-imaging studies (FMRI) and the the ERP studies. The studies outlined in Core C build on our previous research and introduce new lines of inquiry that will inform our understanding of later development in both normal and atypical populations. This new core will centralize our resources and provide a clearly-defined forum for the discussion and investigation of cross-population and investigation of cross-population hypotheses with respect to the development and integration of these basic cognitive systems.

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

Project Title: EARLY DEVELOPMENT: WILLIAMS OR DOWN SYNDROME CHILDREN Principal Investigator & Institution: Mervis, Carolyn B.; Distinguished University Scholar and Pro; Psychological and Brain Sciences; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-MAR-1993; Project End 31-MAY-2004 Summary: The general objective of the proposed research is to delineate the developmental relations between language and cognition. The research will focus on early linguistic and cognitive development by three groups of children: children with William syndrome, children with Down syndrome, and normally developing children. Previous researchers have argued that children with Williams syndrome have language skills that exceed their cognitive skills, whereas children with Down syndrome have cognitive skills that are more advanced than their language skills; in general, normally developing children have equivalent levels of linguistic and cognitive skills. Because of the differences in the general nature of the relations between language and cognition for the three populations, inclusion of all three in a single study provides a unique opportunity to investigate the universality or non-universality of specific relations among language and cognition. The proposed research consists of a five year longitudinal study with supplemental studies conducted at specific points in development. Both observational and experimental methodologies will be used. There are four specific objectives. First, a series of general and specific relations between language and cognition will be examined. Second, the reference of children's earliest words will be explored, using observational, quasi- experimental, and experimental procedures. Third, the development and use of lexical operating principles by children with mental retardation will be considered. Finally, general issues of development by children with Williams syndrome and Down syndrome will be addressed. The research will have implications both for theoretical models of the relation between language and cognition and for the design of early cognitive and language intervention for children with developmental disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELECTOPHYSIOLOGICAL STUDIES OF THE BRAIN Principal Investigator & Institution: Mills, Debra; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: Our broad goals are to study the biological constrains and the role of experience in setting up functionally specialized neural systems in normal development and to study the nature and extent of changes in this process in cases of abnormal development. An important approach is to study changes in brain organization that occur as a function of chronological age and to contrast these with changes linked to specific abilities when age is held constant. The variability occurring in normal development provides on opportunity to address this issue. The study of abnormal development, as in the case of language impaired (LI) children, children with foci brain lesions (FL children) and children with Williams Syndrome, provide another opportunity to link specific changes in neural development with alterations in specific cognitive processes. To this end we will record event-related potentials (ERPs) from over several specific cognitive processes. To this end we will record event-related

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potential (ERPs) from over several regions making comparisons within and between the cerebral hemispheres in a series of studies designed to assess different aspects of language, spatial, and attentional processing. The specific aims are to assess the hypotheses that (a) different neural systems mediate semantic and syntactic aspects of language processing from an early age, (b) neural systems important in grammatical processing are more vulnerable to early experience than are the systems that mediate semantic processing and these may be abnormally organized in children LI, focal brain lesions, and Williams Syndrome (c) some of the patterns of abnormal brain activity linked to language processing in the clinical populations may be elicited in normal children under stressed conditions related to perceptual or temporal difficulties (d) examine the timing and organization of neural systems that mediate different aspects of visuo- spatial processing within the dorsal and ventral visual streams in children who show abnormal spatial abilities (WMS and FL with RH damage), and (d) functional organization within the right hemisphere for spatial processing may be affected by abnormal organization of neural streams in children who show abnormal spatial abilities processing within the dorsal and ventral visual streams in children who show abnormal processing with the dorsal and ventral visual streams in children who show abnormal spatial abilities (WMS and FL with RH damage), and (d) functional organization within the right hemisphere may be affected by abnormal organization within the left hemisphere in children with abnormal organization for language, LI, WMS and a subset of children with FL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF GENES IN WILLIAMS SYNDROME DELETION REGION Principal Investigator & Institution: Francke, Uta; Professor; Genetics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): With the Human Genome Project promising to provide a catalog of all human genes in the near future, the main challenge of research in the next century is that of functional genomics. The processes that control gene activation and repression in a developmental-stage and cell-type specific manner are fundamental to understanding normal development and discovering the causes of human disease. Spontaneously recurring microdeletions are ideal for a systematic study of the downstream effects of hemizygosity for the defined set of genes in the deletion. Williams-Beuren syndrome (WBS), a neurodevelopmental disorder with a distinct profile of cognitive and behavioral features serves as a model system to study the genetic and molecular basis of cognition, speech, language, and visuo-spatial processing. WBS is caused by recurrent uniform deletions of 1.6 Mb of DNA from chromosome 7q11.23, that arise by inter- or intrachromosomal recombination between flanking duplicated regions. Within the deletion, 16 genes have been identified and characterized. They function as transcription factors, in DNA replication, chromatin assembly, translation, signal transduction and as structural proteins. Only one, the elastin gene has been linked to a specific manifestation, supravalvular aortic stenosis. To evaluate the functional consequences of hemizygosity for the other genes, humans with partial deletions will be identified and mouse models generated with corresponding deletions in the conserved syntenic region on mouse chromosome 5. Target genes of transcription factors and signaling molecules will be identified by microarray studies, comparing gene expression patterns in various tissues from affected humans and deletion mice. Development of a molecular phenotype of WBS links cognitive

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neuroscience to molecular genetics. Insights gained into the molecular pathways, that lead from the chromosomal deletion to the specific cognitive, behavioral and learning disabilities may have relevance for common developmental disorders, such as attention deficit/hyperactivity disorder and autism, as well as for understanding normal developmental processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHENOTYPE

GENETICS

OF

TURNER

SYNDROME

NEUROCOGNITIVE

Principal Investigator & Institution: Zinn, Andrew R.; Assistant Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-MAR-1997; Project End 31-JUL-2007 Summary: (provided by applicant): Turner syndrome (TS) is a human genetic disorder involving females who lack all or part of one X chromosome. Classic TS features include short stature, infertility, and anatomic abnormalities. More recently, characteristic neurocognitive deficits in nonverbal domains such as visual-spatial abilities have been recognized as part of the syndrome. Our original grant proposed to map loci responsible for specific TS cognitive and physical features by collecting a large number of subjects with heterogeneous X chromosome deletions, mapping the deletions using molecular methods, and thoroughly analyzing associated phenotypes. Rigorous statistical analysis showed that deletions of certain regions of the short arm of the X chromosome were associated with specific TS phenotypes, including neurocognitive deficits, short stature, and ovarian failure. Cognitive and physical aspects of the phenotype were dissociable. We narrowed the location of gene(s) responsible for a major component of the TS neurocognitive phenotype to an interval of the distal short arm (Xp) spanning only ~1% of the X chromosome. This same interval has been previously shown to contain a gene termed SHOX, deletions or mutations of which cause short stature and other TS skeletal abnormalities. Following the paradigm of Williams syndrome, another complex genetic disorder with characteristic physical and cognitive phenotypes, we reasoned that TS represents a genetic and phenotypic continuum associated with X chromosome deletions. Furthermore, physical phenotypes associated with SHOX deletions could be used to ascertain a population of subjects with small distal Xp deletions in and around the TS neurocognitive critical region without bias with regard to their neurocognitive phenotypes. Fine-mapping these subjects' deletions will allow us to narrow the TS neurocognitive critical region to a specific gene(s). Furthermore, characterizing the neurocognitive profile of subjects with SHOX point mutations or distal Xp deletions limited just to SHOX will allow us to critically test whether this known TS gene also plays a role in the neurocognitive phenotype. The proposed study takes advantage of our existing clinical collaborations as well as large referral populations for SHOXassociated disorders in Dallas and Philadelphia to obtain a sufficient sample size of unrelated distal Xp deletion subjects for rigorous statistical analyses. The project will combine molecular characterization of subjects with detailed cognitive evaluations to elucidate the role of SHOX or other pseudoautosomal gene deficiencies in the TS neurocognitive phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LANGUAGE COMPETENCE AND PERFORMANCE IN WILLIAMS SYNDROME Principal Investigator & Institution: Zukowski, Andrea L.; Assistant Research Scientist; Linguistics; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): The long-range goal of this research program is to characterize how much of a grammar is attainable in the context of cognitive limitations that last throughout the lifespan. The research focuses on people with Williams syndrome (WS)--a neurodevelopmental genetic disorder which results in moderate mental retardation, but impressively good language skills. Early evidence suggested that the WS profile could be taken as evidence for language modularity. However, recent research has documented poor performance in some aspects of WS morphosyntax, and these findings have been taken to challenge the modularity claim. Some researchers have even implied that we can expect to learn nothing about how language acquisition normally works by studying WS. But the potential implications of WS for understanding language acquisition do not depend on perfect language performance. Poor performance does not necessarily reflect impairments in underlying knowledge. The crucial question with regard to WS is not whether cognitive limitations have an influence in how one performs in tests of language abilities, but rather, what kind of grammatical competence system is one capable of achieving in the context of cognitive limitations? To answer this question, it is critical to localize the source of any problems as either residing in the competence system or in the performance systems that are called upon in comprehension, production, judgment, etc. The overall aim of the proposed work is to flesh out the linguistic profile of people with WS in both breadth and depth, in order to inform these questions. This aim is achieved by both investigating poor performance in specific language tasks in order to identify the locus of the difficulty, and by examining specific new areas of linguistic knowledge in this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENTAL PSYCHOPATHOLOGY

RETARDATION

AND

DEVELOPMENTAL

Principal Investigator & Institution: Cohen, Donald J.; Yale Child Study Center; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUL-1978; Project End 28-FEB-2005 Summary: This application requests five years of continued support for a Multidisciplinary program of research on Mental Retardation and Developmental Psychopathology. The Program emphasizes the interaction of neuromaturational genetic, and environmental factors in the emergence, course of specific syndromes as well as the development of individuals with mental retardation and developmental disorders. The program is unified by shared theoretical perspectives, methods, and research strategies. Processes are studied at various levels, including genetic, molecular, brain functioning, neuropsychology, clinical symptomatology, and adaptation and competence of retarded individuals as whole people. A particular concern is the interaction of neurobiological and neuropsychological factors in the understanding and aspects of competence as well as disability. The research Project areas focus on major domains of theoretical and clinical importance in relation to understanding of mental retardation and developmental disorders. Regulation of arousal and attention to conditions of environmental and biological risk, Interaction of genetic and biological

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factors in the pathogenesis of Tourette's syndrome and associated disorders, Autism and Asperger Syndrome-neurocognitive studies of social development and Neurobiological and developmental processes in genetic forms of mental retardation: Williams, PraderWilli, and autism. The Program Project includes a range of specific syndromes and disorders, including autism, Asperger, Tourette's Syndrome, Obsessive-compulsive disorder, Attention Deficit Hyperactivity Disorder, Prader-Willi, and Williams syndromes, as well as children with developmental difficulties related to exposure to drugs and psychosocial adversity. These conditions are studied as important in their own right as clinical conditions and also as models for studying gene-environment interaction, developmental mechanisms, and developmental process over the course of life. Neuropsychological, behavioral, genetic, brain-function, developmental and other findings an be compared across the various diagnostic groups, to clarify basic mechanisms (such as the development of social competence) and clinical correlates (such as arousal/attentional or obsessive-compulsive symptomatology). The Program is also supported by Core Research Resources: Assessment and Biostatistics and Methodology. These core resources provide state-of-the-art collaboration and consultation for all of the Project Areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC BASIS OF WILLIAMS SYNDROME Principal Investigator & Institution: Ruddle, Frank H.; Professor of Biology and Human Genetics; Molecular and Cellular Physio; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by the applicant): Williams Syndrome (WS) is an autosomal dominant genetic condition characterized by an ensemble of physical, cognitive, and behavioral traits. The syndrome has been mapped to 7ql1.23, where genetic causation is attributed to a microdeletion of approximately 1.5 Mb in length. To date, 17 genes have been identified in the haplo-insufficiency region, which serve as specific candidates for the multiple features of the condition. While the 1.5 Mb deletion occurs most commonly, smaller more informative deletions occur at a lower frequency and facilitate the presumptive identification of genes that are causal to specific cranio-facial and neurological attributes of WS. Currently, deletion mapping implicates genes near the telomeric terminus of the deletion, as most critical in phenotype causation. Three genes are viable candidates. These are CLIP-115, BEN, and TFII-I. CLIP-115 is a cytoplasmic linker protein, while TFII-I and BEN are closely related helix-loop-helix transcription factors. We have recently isolated the BEN gene in mice in a search for factors that bind to the early enhancer of the developmentally important Hoxc8 gene. This implicates BEN and TFII-I as candidate developmental factors, deficiencies of which may be expected to generate the symptomology of WS. In an effort to establish the molecular basis of WS, we will use chromosome engineering and other transgenic methodologies to simulate a haplo-insufficiency for these three candidate genes in mice. The mutant mice will be examined for physical, biochemical, and behavioral phenotypes that are typical of persons with WS. In this way, we hope to implicate definitively the three candidate genes singly or in combination as casual factors in WS. This will represent the first step in establishing the molecular genetic basis of WS. The second step will involve the discovery of downstream genes regulated by the transcription factors BEN and TFIII. We believe certain genes in this category may be profoundly deregulated in the WS haplo-insuficiency condition, and are therefore most probably the immediate causal factors in WS. The establishment of the developmental genetic basis of WS is important

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Williams Syndrome

beyond the understanding it brings to WS itself. The identification of genes that regulate behavior allows further investigation of genetic polymorphisms of these genes that may be causal to less severe behavioral conditions or to variations in behavior within a range considered normal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBEHAVIORAL STUDIES OF LANGUAGE IMPAIRMENT Principal Investigator & Institution: Wulfeck, Beverly; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: A growing body of research is challenging the notion of specific language impairment. Our investigations of language-impaired children (LI) reveal limitations in language, but neurologic abnormalities and deficits in other cognitive domains have also been noted. Further insights require study of non-verbal cognition as well as language, and the neural substrates that subserve them. Because LI can extend into adulthood, we will include adolescents with LI in our studiers. The major aims of this project are: 1. Study basic language processing abilities across a wider age range (7- 16) and examine higher order language to determine how early LI impacts on later language use and literacy. 2. Test for associations and dissociations and differentiate knowledge from processing deficits. 3. Study attention, spatial localization, laterality, visual memory and mental rotation abilities and examine for selective sparing and/or impairment across non-verbal cognitive domains. 4. Test for patterns of association and dissociation between language and cognition. 5. Conduct fMRI and ERP studies of language using paradigms tightly yoked to behavioral measures to examine languagebrain mappings in LI children. 6. Conduct fMRI and ERP studies of spatial cognition and attention using paradigms tightly yoked to behavioral measures to examine for patterns of sparing and impairment in non-verbal cognition. 7. Conduct longitudinal studies of LI to examine developmental trajectories for evidence of differential catching up or continued impairment across language and cognitive domains. 8. Compare LI results to results from children with different etiologies including early focal brain injury (FL), Williams or Down Syndrome, and FL Variants (i.e. bilateral or late onset brain lesions) to further characterize the contrasting behavioral profiles noted in the last funding period and determine whether these are associated with alternative forms of brain organization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROBIOLOGY AND DEVELOPMENTAL PROCESSES IN DEVELOPMENTAL DISABILITIES Principal Investigator & Institution: Schultz, Robert T.; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002 Summary: SUBPROJECT ABSTRACT NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROMORPHOLOGICAL CHARACTERIZATION OF WILLIAMS SYNDROME Principal Investigator & Institution: Jernigan, Terry L.; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2002 Summary: The existing resource of longitudinal data from the NHLBI Twin Study, the relatively large sample size, the use of comprehensive and state-of-the-art measures of brain function and structure will provide us with an unprecedented opportunity to examine previously unexplored associations between CVD risk factors and indices of brain aging in older twins. 1. Conduct a fourth exam in an estimated 641 individuals including, 120 monozygotic (MZ) and 120 dizygotic (DZ) intact pairs, that will repeat a core battery of assessments given in previous examinations and add new neuropsychological tests and cerebral NM scanning. 2. Evaluate the prospective and cross-sectional relationships of cardiovascular risk factors collected over 23 to 25 years of follow-up (e.g., blood pressure, lipids, obesity, smoking) and MRI indices of brain morphology assessed at the fourth exam. 3. Determine the extent that twins discordant for essential hypertension or non-insulin dependent diabetes mellitus (NIDDM) or cardiovascular disease (CVD) show different MRI profiles. 4. Characterize the neuropsychological changes In performance from Exam 3 to Exam 4 and determine the contribution of genes and the environment to stability or change. 5. Use the data from exams I to 3 to investigate prospective relationships between CVD risk factors and decline in cognitive performance from Exam 3 to Exam 4. 6. Determine the heritability of the new measurements obtained for the first time at the fourth examination cycle [e.g., MRI measures of white matter hyperintensities (WMHIs), infarct area and location, and ventricular volumes]. 7. Conduct multivariate genetic analyses to determine the contribution of genes and the environment to the covariation among physical, physiological, and neuropsychological variables. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUMERICAL DEFICITS ACROSS MULTIPLE GENETIC DISORDERS Principal Investigator & Institution: Simon, Tony J.; Research Assistant; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The central aim of the proposed research is to investigate whether there is a common basis for the numerical cognition deficits associated with three neurogenetic disorders: Turner, Williams, and full mutation fragile X syndromes. Despite many differences, numerical deficits have been consistently reported in individuals with Turner, Williams, full mutation fragile X, and 22q11.2 deletion (velocardiofacial/DiGeorge) syndromes, among others. The investigators hypothesize that some key aspects of visuospatial function are disturbed in each of these syndromes, and characterization of these basic processes will generate explanations of, and possibly indicate treatments for, these numerical deficits. On the other hand, the differences among these genetic syndromes will allow the investigators to control for a range of critical factors such as intelligence level, brain volume, cardiac status, and other cognitive performance domains. This project aims to study seven to fourteen year old children with Williams, Turner, and full mutation fragile X syndromes in parallel with a study of 22q11.2 deletion syndrome children already being carried out by the principal investigator. This will constitute the first parallel study of children with all of these disorders using the same methodology. Thus it has the potential to reveal critical information about a putative "common pathway" for foundational numerical cognitive competence. Little is known about why a set of neurogenetic disorders that produce such different physical and intellectual outcomes should share what appears to be a common deficit in the numerical cognition domain. The investigators' hypothesis is that the disorders all create some form of anomalous in brain development that affects the

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Williams Syndrome

parietal lobes, as well as other brain areas, in such a way as to disturb the normal development of visual/spatial cognition. Therefore, the investigators propose a program of research in three genetic disorders: Turner, Williams, full mutation fragile X syndromes with the following aims: (1) Characterize the cognitive deficit with performance tests; (2) Specify the volumetric changes in brains of children with these disorders; (3) Determine, via diffusion tensor imaging, white matter anomalies that might contribute to cognitive dysfunction; and (4) Directly measure, via functional magnetic resonance imaging (fMRI), cortical activity as children attempt visuospatial and numerical cognition tasks. The investigators expect that the results of these studies will provide the first extensive explanation of the similarities and/or differences in foundational numerical cognitive processes that exist among these different disorders. Findings are likely to indicate critical neurocognitive factors in the development of normal and disturbed early numerical ability. It should be possible to use these results to develop interventions for children with numerical disabilities and improved teaching methods in the numerical domain for typically developing children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OBJECT AND SPACE PROCESSING: A DEVELOPMENTAL PERSPECTIVE Principal Investigator & Institution: Paul, Brianna M.; Center for Human Development; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Fundamental human abilities such as recognizing a loved one, or navigating with a map depend integrally on the extra striate visual cortex. Interestingly, the developmental course of this system is a protracted one, with certain skills continuing to develop into the teenage years. In the adult, higher order visual functions can be divided according to the neuroanatomical subsystems ("what" or ventral occipitotemporal, and "where" or dorsal occipitoparietal) on which they rely. Though a great deal is known regarding these systems in the adult, little is known about the development of these pathways and the emergence of this adult-like dissociation. The proposed studies, therefore, aim to address these uncertainties by utilizing a matched-task paradigm. The "what" task involves perceptual object-matching and the "where" task involves perceptual location-matching; these tasks are matched in that they are identical with respect to stimuli, required response and level of difficulty in adult controls. Study 1 will compare patterns of reaction time performance on these tasks for typical adults and children, with the goal being to explicate developmental changes and examine the emergence of the adult-like behavioral dissociation in what/where processing. Study 2 utilizes functional magnetic resonance imaging (fMRI) to characterize and compare developmental change in the neural substrates underlying "what" and "where" visual processing. Knowledge regarding the relationship between behavioral changes in these systems manifested during development and functional brain activity will allow for the systematic examination of alternative developmental trajectories of these higher order visual functions. Specifically, Study 3 will examine behavioral performance indices and functional brain activity in individuals with congenital/genetic abnormalities (Williams Syndrome) and in individuals who have experienced a prenatal stroke. These populations, thus, afford us the unique opportunity to begin to understand the nature of plasticity and reorganization in these critical perceptual systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERIODIC LIMB MOVEMENTS IN WILLIAMS SYNDROME Principal Investigator & Institution: Mason, Thornton B.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Candidate's Plans/Training: The candidate plans a career as a patient-oriented researcher bridging pediatric medicine, sleep disorders, and genetics. Training will include formal epidemiology and biostatistics course work, structured laboratory work, and closely mentored completion of the research protocol. Environment: The outstanding pediatric research setting at UPCHP includes expertise in sleep disorders, clinical genetics, and molecular biology. These areas of strength will be complemented by the clinical and basic science research support offered by the Center for Sleep and Respiratory Neurobiology. Pennsylvania's Center for Clinical Epidemiology and Biostatistics will provide formal course training. Collectively, the environment is uniquely suited for this training award. Research: PLMS are rhythmic and highly stereotyped flexion movements of the extremities. PLMS may produce significant sleep disruption, and occur over a range of patient ages and settings. The pathophysiology of PLMS is unknown. Although family studies suggest a genetic basis for some cases of PLMS occurring with restless legs syndrome, no associated genes or gene products have been identified. Because preliminary data support the paucity of PLMS among control subjects and the prominence of PLMS in children with WS, this special group of patients may represent a unique opportunity to allow identification of a gene(s) involved in PLMS. WS is a human developmental disorder caused by a microdeletion of multiple genes in a distinct region of chromosome 7 (7q11.23). In this protocol, I propose to test the specific hypothesis that children with WS manifest genetically determined PLMS that is responsive to dopaminergic therapy. To this end, the primary aims of this proposal are: 1) to determine the prevalence of PLMS and the degree of variability in children with WS; 2) to determine whether PLMS are sensitive to dopamine therapy as are PLMS to other populations; and 3) to determine if there is a specific PLMS-genotype correlation in patients with WS. This protocol will provide new insights into WS as a model for PLMS in the general population, and may identify a specific gene(s) implicated in the etiology of these movements. Further, it will provide training necessary to conduct rigorous patient-oriented research in the area of genetics of sleep and its disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHENOTYPE/GENOTYPE CORRELATIONS FOR CONTIGUOUS GENE DELETION SYNDROMES Principal Investigator & Institution: Lupski, James L.; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POTENTIAL ROLE OF TFII-I IN IMMUNODEFICIENCY Principal Investigator & Institution: Roy, Ananda L.; Professor; Pathology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2005

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Williams Syndrome

Summary: TFII-II is an important multi-functional transcription factor that links events to transcription in several genes. TFII-I is constitutively associated with Bruton's tyrosine kinase (Btk), a non-receptor tyrosine kinase that is essential for normal B cell function, as its mutation causes X-linked agammaglobulinemia (XLA) in humans and Xlinked immune deficiency (xid) in mice. We propose that TFII-I is an important and novel component in linking Btk-mediated signaling to transcription in B cells. Furthermore, the TFII-I gene gets deleted in William's syndrome (WS) which is a neurodevelopmental disorder with multi-system manifestations, including supravalvar aortic stenosis, hypercalcemia in infancy, mental retardation and cognitive defects. Thus, TFIII appears to be involved in two genetic disorders: William's Syndrome and X-linked agammaglobulinemia (XLA). Knowledge gained from these studies may help us better understand a critical Btk dependent pathway that links B cell receptor mediated signal transduction to B cell specific transcription. These studies may also ultimately help identify potential target gene(s) that are affected by mutations in Btk. Importantly, these studies may establish possible connections between the neuro-developmental disorders (as in WS) and immuno-developmental disorders (as in XLA). Toward a better understanding of TFII-I function in Btk mediated immune response, we will first map the region(s) in TFII-I important for its physical and functional interactions with BTK. We will determine by deletion and point mutation the region(s) in TFII-I that is important for its interaction with Btk, followed by mapping the sites in TFII-I that are tyrosine phosphorylated by Btk in vitro and in vivo by a combination of site directed mutagenesis, phosphopeptide, finger printing, and mass spectrometric analysis. We will also analyze these mutants in functional transient transfection assays. To determine the functions of TFII-I and its biochemical interactions with Btk in B cells, we will employ in vivo transcriptional analysis. To determine the functions of TFII-I and its biochemical interactions with Btk in B cells, we will employ in vivo transcriptional analysis followed by the interaction studies by co- immunoprecipitation and ectopic expression of mutant forms of TFII-I in B cells. We will also stably express wild type and mutant forms of TFII-I, and Btk in B cell lines, and genetically delete TFII-I from chicken B cells. Finally, to ascertain the localization of TFII-I in the absence and in the presence of non-activated versus activated Btk, first, we will co-express various mutants of TFII-I with Btk in COS cells. Subsequently, we will employ freshly isolated primary splenic B cells derived from wild type, xid and Btk-/- mice and study the localization and tyrosine phosphorylation of TFII-I in the absence and in presence of B cell receptor signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PSYCHOPATHOLOGY IN YOUNG PEOPLE WITH MENTAL RETARDATION Principal Investigator & Institution: Tonge, Bruce J.; Monash University Faculty of Medicine, Nursing & Health Sciences Melbourne, Vic, 3181 Timing: Fiscal Year 2002; Project Start 20-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Families caring for young people with mental retardation face major burdens of care if the young person also has emotional and behavioural problems. Serious mental health problems are 2-3 times more common in young people with mental retardation, which apart from the personal distress and loss opportunity it causes the child and family, is also a major cost to our community. This project is intended to assist young people and their careers by providing new information about the factors contributing to these mental health problems and how they develop over time. The project makes use of the existing internationally unique epidemiological longitudinal study (the Australian Child and Adolescent Development

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Study ACAD) which has followed a group of young people with mental retardation aged 4-18 for the last eight years, from childhood through adolescence as they move into young adult life. The ACAD study has collected an extensive range of biopsychosocial data on these young people and their families. This project will examine the unique database produced by the ACAD study using state-of-the-art statistical techniques in to order to elucidate the biopsychosocial risk and protective factors relating to the progression and development of mental health problems in this under researched and under serviced population. It is expected that the results of such analyses will directly contribute to the development of appropriate intervention and prevention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUALITY OF LIFE OF ADOLESCENTS AND ADULTS WITH MILD INTELLECTUAL HANDICAPS Principal Investigator & Institution: Pober, Barbara R.; Associate Professor of Genetics and Pedi; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COFILIN/ADF

REGULATION

OF

ACTIN

FILAMENT

ASSEMBLIES

BY

Principal Investigator & Institution: Mcgough, Amy M.; Assistant Professor; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Actin plays a central role in cell motility. As cells move in response to external signals, the cytoskeleton is constantly remodeled. For this process to continue, actin subunits must be continuously recycled to the leading edge. Although the assembly rates of actin in vitro are extremely rapid, the pointed end disassembly rate constant measured in vitro is far too slow to recycle the monomers necessary for this process to continue. Recent studies have identified a family of actin binding proteins that play a central role in actin filament dynamics in cells by both severing filaments and increasing the rate of disassembly from ends. Cofilin and ADF (Actin Depolymerizing Factor) are members of a large family of proteins that is conserved across the complete spectrum of eukaryotic organisms. They are key players in actin filament turnover in yeast and are essential in all organisms tested. Failure to regulate cofilin properly leads to Williams syndrome in man, while point mutations in cofilin produce paralysis in Caenorhabiditis elegans. Thus, elucidating how cofilin regulates actin assembly has important implications for understanding both normal and diseased states in cells. In electron cryomicroscopy studies published last year, I showed that cofilin dramatically alters F-actin structure when it binds. The purpose of the proposed research is to test the hypothesis that this effect on F-actin structure represents a novel mechanism for regulating actin dynamics and assembly in cells. The first goal of this study is to model cofilin/F-actin interactions in greater detail. Cofilin will be labeled with gold on specific residues which will be used as markers to accurately position the x-ray model in our reconstruction. In addition, we will extend the resolution of the current reconstruction beyond its present limit (27 Angstrom units) using improved experimental and computational methods. The second goal of this proposal is to use both geneticallyengineered and naturally-occurring variants to identify the specific residues that endow cofilin with its unique actin regulatory properties. The third goal is to explore the

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Williams Syndrome

molecular basis of a cofilin-dependent muscle disease in C. elegans by determining how cofilin mutants responsible for this disease interact with F-actin. This project will test the hypothesis that cofilin's effects on actin filament structure are central to its function in multi-cellular organisms. Our fourth goal is to explore the hypothesis that cofilin promotes the formation of alternative actin assemblies in cells through its mode of binding to the filament. This will involve structural studies of non-helical cofilin/actin assemblies produced in vitro as well as of cofilin/actin rods found in the cytoplasm and nuclei of diseased cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE DEVELOPMENT

OF

ADF

PHOSPHORYLATION

IN

NEURONAL

Principal Investigator & Institution: Bamburg, James R.; Professor; Biochem and Molecular Biology; Colorado State University-Fort Collins Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-DEC-1984; Project End 31-MAR-2004 Summary: (VERBATIM FROM APPLICATION): Directed neuronal growth depends upon the dynamics of actin filaments within the highly motile growth cone. Although actin dynamics are regulated by the complex interactions of many actin-binding proteins, the high turnover rate of actin filaments in vivo is dependent upon proteins in the actin depolymerization factor (ADF)/cofilin (AC) family. AC proteins are essential in all eukaryotes and are enriched within neuronal growth cones. Furthermore, overexpression of ADF in neurons leads to an enhanced rate of outgrowth that is sustained for days. AC proteins are phosphorylated on a single regulatory site. Their phosphorylation and dephosphorylation are common targets of signaling pathways linking external signals to actin cytoskeletal reorganization. Enhanced dynamics of this phosphocycle, without a net change in the phosphorylation state of the AC proteins, often accompanies induction of ruffling membrane. Vertebrate AC proteins are phosphorylated by LIM kinases for which they are the only known substrates. Many growth factors and guidance cues signal in part through the rho family GTPases, each of which has specific targets for actin organization, but all of which target at least one member of the LIM kinase family. Hemizygosity of LIM kinase I causes Williams syndrome, a visuo-spatial cognitive defect resulting from aberrant neuronal migration in the human brain. Thus we hypothesize that the response of growth cones to various guidance cues is modulated by the regulation of AC activity, which is likely to be the final integrator of multiple signaling pathways. We propose to use a combination of molecular, cellular, immunological, and ultrastructural approaches to test the hypothesis that phosphorylation regulation of ADF activity is required for initiation of neuritic outgrowth cone pathfinding in response to attractive or repulsive guidance cues. Tropomyosin isoforms, which may compete with AC for actin filament binding, and Arp2/3, which caps pointed ends of actin and may regulate the ability of AC to depolymerize the filaments, will be localized along with AC and phosphorylated AC in growth cones undergoing a turning response. We will also test the hypothesis that guidance cues signal via bifurcating pathways that regulate both AC phosphorylation and dephosphorylation through activation of PI-3 kinase, and we will isolate and characterize the phosphatase involved. Adenoviral mediated gene transfer is a major tool to be used in sorting out the signal transduction pathways in regulating AC. These studies will advance our understanding of nerve growth cone guidance and the design of agents that allow neurons to grow and regenerated in a normally non-permissive environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOCIAL BEHAVIOR OF YOUNG CHILDREN WITH WILLIAMS SYNDROME Principal Investigator & Institution: Klein-Tasman, Bonita P.; Assistant Professor; Psychology; University of Wisconsin Milwaukee Graduate School Milwaukee, Wi 532010340 Timing: Fiscal Year 2004; Project Start 15-MAR-2004; Project End 28-FEB-2005 Summary: (provided by applicant): The study of children with Williams syndrome, a neurodevelopmental disorder with a known genetic basis, is fascinating for those interested in understanding the genetic underpinnings of behavior. The unusual peaks and valleys in cognitive abilities, coupled with increasingly specific delineation of the genes deleted in individuals with this disorder, have led to discoveries of likely relations between specific genes and cognitive abilities. Evidence is mounting that children with Williams syndrome also have distinctive personality characteristics, including a strong interest in interacting with other people. In light of this sociability, some researchers have pointed to Williams syndrome as a stark contrast to autism spectrum disorders, where reciprocal social interaction is an area of specific weakness. However, given that children with Williams syndrome have been shown to be sociable but not necessarily socially successful, the nature of their abilities warrant further investigation. The overall objective of this investigation is to provide a more complete description of the sociocommunicative behavior of young children with Williams syndrome, so as to gain a more comprehensive sense of the characteristics that are distinctive to the disorder. To achieve this objective, the proposed investigation will examine the behavior of children with Williams syndrome in a standardized context, using the Autism Diagnostic Observation Schedule. Participants will be 2 groups of 35 2 1/2- to 5 1/2- year-olds, matched for chronological age, developmental level, and gender. One group will consist of children with Williams syndrome; the other group will consist of children with other developmental disabilities. The specific aims are to: (1) Describe the sociocommunication abilities of young children with Williams syndrome and determine the distinctiveness of their pattern of abilities. (2) Determine the relation between chronological age, intellectual functioning, and the presence of deficits in communication and reciprocal social interaction. (3) Explore the extent to which the behavior seen in young children with Williams syndrome overlaps with the diagnostic category of Autism Spectrum Disorders and the nature of this overlap. The results of this investigation should lay a foundation for increased understanding of relations between genes, personality, and social behavior and facilitate the design of more effective social skills interventions for children with Williams syndrome or other developmental disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SOCIAL COGNITION IN WILLIAMS SYNDROME Principal Investigator & Institution: Tager-Flusberg, Helen B.; Professor of Anatomy and Neurobiology; Anatomy and Neurobiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 29-SEP-1995; Project End 31-AUG-2005 Summary: The goals of the proposed research are to systematically investigate social information processing capacities in Williams syndrome (WMS). Earlier work has shown that people with WMS have good face processing skills and language ability. While they are not spared on classic theory of mind tasks, studies we conducted in our ongoing research, during the current award period, suggest that they are better than

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Williams Syndrome

matched comparison groups in reading mental state information in eyes. We plan to extend this work by investigating foundational capacities in adolescents and adults with WMS to process information in two main channels for social communication: faces and vocal prosody. A series of experiments will be conducted with groups of adolescents and adults with WMS, matched on age, gender, IQ and receptive vocabulary to adolescents and adults with non-specific mental retardation, and to age and gender matched non-retarded controls. The experiments test the hypothesis that people with WMS are relatively spared compared to the matched mentally retarded controls in: (A) Face recognition; we also predict that they process faces using the same holistic representations as normal adolescents and adults; (B) Voice recognition; and the use of prosody in linguistic processing of both word and sentence ambiguity; (C) Attributing social-mental state information to faces; (D) Attributing mental state information to vocal prosody; (E) Recognizing people and attributing mental state information to dynamically presented social stimuli; (F) Expressing affect and empathy to dynamically presented emotionally charged events at physiological, and behavioral (but not cognitive) levels. We are especially interested in investigating the relationships between face processing skills and use of linguistic prosody, and parallels in the ability to attribute social or mental state information to faces and prosody -the two primary channels for interpersonal communication and social interaction. Our research also explores these links between faces and vocal prosody in different modalities: in the perception and expression of emotion. These studies will lay the groundwork for future studies that will address how these capacities develop in children with WMS, and the neural bases of these social information processing skills using functional brain imaging methodologies. This research will significantly advance our understanding of the phenotypic characteristics of people WMS, which has important implications for enhancing their everyday lives. Together, this program of research on WMS will provide a unique contribution to theoretical and empirical work in the newly emerging field of social cognitive neuroscience. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF PROSODY.AUTISTIC SPECTRUM DISORDERS Principal Investigator & Institution: Paul, Rhea; Professor; Communication Disorders; Southern Connecticut State University 501 Crescent St New Haven, Ct 06515 Timing: Fiscal Year 2004; Project Start 23-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The proposed project will provide 50% salary support for five years to release the applicant from teaching and other faculty responsibilities at Southern Connecticut State University and allow her to work on a series of patient-oriented research studies and to mentor beginning speech-language clinicians at the Yale Child Study Center. The candidate is a productive researcher (60 papers in refereed journals) who has, for the past 16 years, been teaching at state universities with heavy teaching loads. This award would provide her with the opportunity to engage in focused research and mentoring activities in a patient-oriented clinical research environment. The Yale Child Study Center has been active in both research and clinical care of children with autism for more than 20 years. The Center provides both a source of subjects for research and a multidisciplinary clinic that serves large numbers of these children and their families, as well as the opportunities for collaborations with scientists from a broad range of backgrounds. The candidate's longterm goals in this project are: 1) to increase her knowledge and skills in three areas in which specific collaborators have been proposed--instrumental speech analysis and signal detection, neuroimaging, and robotics; and 2) to devote more time and attention

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to patient-oriented research and clinical mentoring. The research career development plan proposed here will result in maximizing the candidate's opportunity to contribute to knowledge and practice in the field of communication disorders in autism. The research plan for this project involves three studies: 1) the study of the production of prosody in grammatical and pragmatic/affective contexts in high functioning individuals with autistic spectrum disorders (ASDs) and appropriate contrast groups, using instrumental analysis and signal detection methodologies, both to better detail prosodic abilities and to work toward the development of a prosodic intervention protocol; 2) the study of the perception of prosody in grammatical and pragmatic/affective contexts in high functioning individuals with ASDs and appropriate contrast groups, both to better detail their abilities and to work toward the development of a protocol that can be tested via functional magnetic resonance imaging for future studies of the neural organization of prosody and to investigate differences in processing strategies between typical subjects and those with ASDS; and 3) the development of a prosodic intervention program with a robotic generalization training phase, to be tested against a traditional intervention program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES ON CHILDREN WITH EARLY FOCAL BRAIN INJURY Principal Investigator & Institution: Bates, Elizabeth A.; Professor; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: Over the past 15 years, we have made significant progress in the study lf language and affective development in children with congenital injuries to one side of the brain (FL). In each behavioral , we have covered evidence of initial deficits, and specific effects of lesion side and site, but these initial deficits are followed by substantial recovery and development, providing strong evidence for behavioral and neural plasticity in this population. Furthermore, we have shown that trajectories of deficit and recovery differ across domains. In language, lesion- symptom correlations exist in the first years of life, but they do not resemble the patterns observed in adults; by 5-7 years of age, specific effects of lesion side and site seem to have disappeared altogether. In spatial cognition, lesion-symptom correlations persist across childhood and adolescence, albeit in a mild form, and continue to resemble the correlations observed in adults. These results are compatible with a large literature on plasticity and reorganization in animals, supporting the view that brain development is a dynamic, responsive and selforganizing system. But they also offer a unique perspective on plasticity and brain organization in humans. We are now well-positioned to take a historic new steps, with convergent use of functional magnetic resonance imaging (fMRI), event-related brain potentials(ERP), combined with analogous "on-line" (timed" behavioral studies of language, spatial cognition and spatial attention. These convergent methods will yield unprecedented information about the "alternative brain plans" that have emerged across the course of development in children with FL. E will also continue to chart language and cognitive development into adolescence, using benchmark "off-line" (untimed" measures of language (including aspects of discourse that re critical to success in school and work), visual-spatial cognition, memory and executive function. On all measures, results for children with FL will be compared systematically to findings for children in other populations, including Specific Language Impairment, Williams Syndrome, Down Syndrome, and new project studying other forms of FL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Williams Syndrome

Project Title: TRAINING PROGRAM IN COGNITIVE NEUROSCIENCE Principal Investigator & Institution: Sejnowski, Terrence J.; Professor; Institute/Neural Computation; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 15-JUL-1999; Project End 30-JUN-2004 Summary: The primary goal of this training program in cognitive neuroscience is to provide advanced graduate students and postdoctoral fellows with interdisciplinary research training in Cognitive Science, Neuroscience and Computation in preparation for a career in cognitive neuroscience. The training program will emphasize interdisciplinary training that involves collaborative research between laboratories using several different techniques. Fifteen faculty at The University of California at San Diego (UCSD) and The Salk Institute for Biological studies will participate in the training program, which builds on eight years of experience with a highly successful Center for Cognitive Neuroscience. Graduate students will be drawn from a large pool of high-quality applicants who are enrolled in the Departmental of Cognitive Science, the Neurosciences Graduate Program, and a new Computational Neurobiology Program in the Department of Biology at UCSD, as well as from other cognate departments including Philosophy, Psychology, and Psychiatry. The resources of several Organized Research Units at UCSD are also available for graduate and postgraduate research training including the Center for Research in Language, the Institute for Neural Computation and the Center for Human Information Processing. The advisory committee that will supervise the training program consists of T. Albright, E. Bates, U. Bellugi, S. Hillyard, M. Kutas, T. Sejnowski, L. Squire, and D. Swinney. The advisory committee will meet with the chairs of all the relevant graduate programs at UCSD to develop a coordinate infrastructure for training in cognitive neuroscience. In addition to the predoctoral training, support for postdoctoral research will focus on new research projects that develop new approaches toward understanding higher brain function. All of the major research areas are represented by the participating faculty on this training grant, including vision, memory, attention, language, sleep development, and neurophilosophy. Training will be provided in a wide variety of methods including electrophysiology, psycholinguistics, functional magnetic resonance imaging computational modeling, and developmental neurobiology. The training in basic research will directly involve studies of humans with mental health problems, including aphasia, autism, Williams syndrome, Downs syndrome and sleep disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHROMATIN

TRANSCRIPTIONAL

ACTIVATION

BY

REORGANIZING

Principal Investigator & Institution: Bartholomew, Blaine; Associate Professor; Medical Biochemistry; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-DEC-2005 Summary: (provided by applicant): Chromatin remodeling serves as a functional key in multiple cellular processes, one of them being the regulation of gene expression through promoting formation of the transcription complex and elongation of the transcription complex. There are several well-documented examples of chromatin remodeling complexes working in conjunction with gene-specific transcription factors to make the DNA accessible to the transcription machinery. In addition, the nucleosome structure is a severe deterrent to the rearrangement of genes required for the production of immunoglobulins. Chromatin remodeling is apparently a mechanism used to tightly

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regulate vertebrate immune systems and is probably the key to the molecular mechanism underlying the "accessibility hypothesis" proposed 15 years ago. Chromatin remodeling is also involved in cell cycle control and interacts with the tumor suppressor protein Rb or retinoblastoma protein. In understanding how SWI/SNF and ISW2 remodel the nucleosome, it is important to know that it does not work randomly on chromatin, but they are recruited or targeted to specific locations by gene-specific transcription factors or repressors. Evidence indicates that chromatin remodeling can be tightly coordinated with DNA modifications such as methylation of DNA and DNA replication. The list of diseases linked to chromatin remodeling continues to grow and includes such diseases as rhabdoid tumours, a very aggressive form of pediatric cancers, breast cancer, leukemia, mental retardation, Williams syndrome, and Rett syndrome. It is not known which subunits of SWI/SNF interact with the transcription activator or how its interaction with the nucleosome may be different when recruited versus indiscriminate binding to nucleosomes. Our research plan is to examine the structure and its relation to function of the SWI/SNF chromatin remodeling complex by a series of approaches that uses either modified DNA or modified histone octamers. We will obtain the 3-dimensional structure of SWI/SNF by electron tomography and determine which regions interact with DNA and histone octamer by linking data from site-directed photoaffinity labeling and proteolysis to the structure. Next, we will determine how SWI/SNF and ISW2 remodel chromatin when recruited to specific sites within nucleosomal arrays by their respective "targeting" proteins. Data on these two different chromatin remodeling complexes suggest that they modulate chromatin structure in significantly different ways both in vivo and in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VISUAL OBJECT REPRESENTATION IN WILLIAMS SYNDROME Principal Investigator & Institution: O'hearn, Kirsten M.; Cognitive Science; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 17-JAN-2003; Project End 16-JAN-2005 Summary: (provided by applicant): This research investigates visual object representation in children and adults with Williams syndrome, as well as normally developing children. People with Williams syndrome have particular difficulty reasoning about the spatial aspects of objects, such as the relations between objects, but seem relatively unimpaired with object category. We hypothesize that this pattern reflects deficits in the representation of the spatiotemporal characteristics of objects, specifically the ability to locate and track multiple objects through time and space, with comparative preservation in their representation of the object's category. Using wellestablished methodologies from adult psychology, we will examine working memory for an object's location and category, object tracking with and without occlusion, and enumeration of multiple objects. These studies will provide a more accurate characterization of the visuospatial deficits in WS, benefiting further research in three important ways. First, it will further our understanding of the functional divisions in object representation and the associated neurophysiological substrates, since researchers have begun to describe the brain abnormalities that accompany this disorder. Second, it will provide a foundation for addressing these impairments clinically. Third, it will increase our understanding of the effects of the gene deletion that is a marker of this syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Williams Syndrome

Project Title: VISUAL-SOCIAL COGNITION IN NEURODEVELOPMENTAL DISORDERS Principal Investigator & Institution: Hadjikhani, Nouchine; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Visual perception of faces is a major component of the "online" processing of social information required for successful interaction with other individuals. Research from cognitive, clinical, and neuroscience approaches suggests that elements of the visual system may be specialized for processing human faces. Of particular interest is the dissociation of face processing from other categories of object processing, and from other components of visual processing, such as motion, attention, and spatial perception. Neuroimaging techniques have the potential to reveal aspects of the underlying architecture and function of visual processing. By combining data from functional magnetic resonance imaging (fMRI), magneto- and electroencephalography (MEG/EEG), and diffusion tensor imaging (DTI), we will be able to better understand the pathophysiology of three neurodevelopmental disorders: autism, Williams syndrome and developmental prosopagnosia. We will explore the dissociations observed in these three groups in order to better understand the fundamental architecture of the parts of the visual system involved with social cognition. Autistic disorder (ASD) and Williams syndrome (WS) seemingly offer complementary patterns of impaired and spared visual function. ASD individuals are poor at social interactions, at facial expression recognition but can perform well on spatial tasks, such as block design. WS individuals are hyper social, perform at ageappropriate levels on the Benton face recognition task, but are severely impaired at block construction and other spatial tasks. Another group of patients, developmental prosopagnosics (DP), are severely impaired in face recognition but are otherwise normal in all other cognitive and social domains. Our research goal will be to characterize the neural system underlying the visual-spatial and communicative aspects of face and object recognition in these three subject populations. We will examine the behavioral profile of ASD, WS and DP, and characterize their cognitive phenotypes in the domain of face processing. We will also analyze the visual cortex organization, at low (retinotopy), and intermediate (hierarchical attention) levels using fMRI, and at high levels (facial and emotional processing), in spatial and temporal domains using MEG and fMRI. Finally, we will examine the architecture of the visual stream subserving facial perception (including the amygdala) using Diffusion Tensor Imaging, Diffusion Spectrum Imaging, and cortical thickness analysis. These aims taken together should provide insight into the relation between behavioral performance and structural/functional characteristics. It should give us additional insight into the pathophysiology face perception disorders, and provide a basis for the development of remedial treatment for deficits in social communication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VOCABULARY EXPANSION IN SEVERE MENTAL RETARDATION Principal Investigator & Institution: Wilkinson, Krista M.; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 30-JUN-2002 Summary: In typically-developing children initially slow, one-at-a-time word learning is followed by an apparent explosion in their lexicon. One estimate suggests that children

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are learning up to nine new words a day. By contrast, for some individuals with severe mental retardation new words enter the lexicon only through slow and deliberate effort. Yet word learning is a foundational component of human development, necessary for advanced linguistic functions and contributing to complex representational skills (e.g., categorization). To the extent that a cognitive disability interferes with word learning, progress in these domains will be correspondingly limited. It is therefore essential to explore in detail the nature of lexical impairments in severe mental retardation. The existence of difficulties in lexical acquisition among individuals with severe mental retardation raises important questions. When rapid vocabulary expansion occurs, what linguistic cognitive processes support that learning? When it does not occur, what skills are deficient or absent? A phenomenon called fast mapping may be of greatest potential relevance for rapid vocabulary expansion. Fast mapping refers to a quick, initial partial understanding of a new word's meaning derived from the context of word use. Fast mapping has been argued to facilitate the vocabulary explosion. This proposed role has received empirical confirmation in typical youngsters and children with Down syndrome. Yet evidence from children with atypical cognition/language has recently challenged the universality of this relation. The Principal Investigator's studies have added to the preliminary evidence of selective deficits in fast mapping among individuals with severe mental retardation, William's syndrome, or specific language impairments. The deficits are most often observed when individuals attempt to apply the principle for the purpose of vocabulary expansion. These recent findings oblige a more systematic analysis of the precise role of the principle in learning outcomes in mental retardation. Is fast mapping at risk in individuals with severe mental retardation, potentially limiting their vocabulary expansion? This application proposes a five-year study of vocabulary expansion and delay, focusing specifically on rapid expansion of an extant, but limited, vocabulary. The proposed series of studies will implement methods developed by the Principal Investigator that will enable the systematic analysis of unresolved questions of lexical expansion in severe mental retardation. The project has four specific aims that will be addressed in the course of four studies: 1) To examine the relation of fast mapping, rapid vocabulary expansion, and nonverbal processes, in order to explore the nature of lexical expansion in severe mental retardation; 2) To explore the points of greatest vulnerability for learning through fast mapping by explicitly taxing participants' skills and observing the ways in which breakdowns occur; 3) To extend the analysis from the commonly examined object-word learning to the acquisition of actionrelated words, to determine whether processes of fast mapping are similar for the two types of form/class categories; 4) To examine the basis underlying children's apparent assumption that new words should and do map to unnamed objects, and whether this assumption is intact among individuals with severe mental retardation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WILLIAMS SYNDROME: BRIDGING COGNITION AND GENES Principal Investigator & Institution: Bellugi, Ursula; Research Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002; Project Start 05-MAR-1996; Project End 28-FEB-2004 Summary: The over-arching goal of the Program Project is to build bridges across disciplines: to link higher cognitive functions, their underlying neurobiological bases, and their molecular genetic underpinnings, using Williams functional magnetic resonance imaging with molecular genetics to study each individual. WMS is a rare genetically based disorder that generally results in mental retardation, distinctive faces, and a specific heart defect. Studies so far suggest that the syndrome also results in a

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Williams Syndrome

characteristic cognitive profile of dissociations both within and across cognitive domains: severe intellectual deficits but relatively spared language; and severe deficits in spatial construction, but remarkable preserved face processing. These dissociations in higher cognitive functioning make WMS an invaluable paradigm for the study of brainbehavior relationships, and for the mapping of brain and behavior phenotypes to the genome. Subproject 0001 WMS, investigating consistency, variability and the bases for dissociations. Subproject 0002 (Neurophysiological Characterization) will investigate the neural correlates of this cognitive profile, using electrophysiological resolution structural and functional magnetic resonance imaging to investigate neural systems in WMS; Subproject 0004 (Cellular and Molecular Architectonics) will address histological changes in neuronal architecture and gene expression in WMS, and Subproject 0005 (The Molecular Genetic Characterization of Williams Syndrome) will seek an understanding of the molecular genetic basis of the disorder. These Diagnostic Methods and Services. Through links across subprojects 0001, 0002, 0003, 0004, 0004 we will begin to define pathways between genotype and cognitive as well as neural phenotype of WMS. Studies of this unusual disorder, Williams syndrome, will provide new opportunities to explore fundamental issues of cognitive neuroscience that relative cognitive functions to brain organization and to their genetic bases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WILLIAMS CHARACTERIZATION

SYNDROME--BRAIN

CYTOARCHITECTONIC

Principal Investigator & Institution: Galaburda, Albert M.; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002 Summary: The purpose of this component project is to carry out a neuroanatomical analysis of the brain in Williams Syndrome (WMS) to shed light on the interface between genetic abnormality and behavioral disorder. The brain in WMS exhibits the following: curtailment of the posterior portion of the forebrain; foreshortening of central sulci dorsally; decrease in volume of the amygdalar nuclei; decreased asymmetry; normal cytoarchitecture; acquired microvascular pathology; laminar-specific decrease neuronal size and increase cell packing density; absence of staining for Elastin in cerebellum; and normal staining for Lim-12 kinase. Curtailment of development of the posterior and dorsal portions of the hemispheres is compatible with the visuo-spatial problem seen in WMS; it may also be compatible with the relative sparing of function linked to more ventral cortices, such as face recognition and language and musical abilities. Acquired microvascular pathology in the same dorsal regions implicates the same behaviors and may represent additive pathology. Involvement of the amygdala, particularly the lateral nuclei, implicates the limbic system and may contribute to the personality typical of WMS. Decrease in cell size with increase in cell packing density, together with a smaller brain, suggests an overall paucity of projection neurons with accompanying changes in connectivity. The absence of Elastin staining but normal Lim1 kinase staining indicates a differential effect off hemideletion on gene expression. Additional brains will be collected. Appropriate sections will undergo semi-automated image processing for cell size and cell numbers. We will also look at differences between dorsal and ventral cortical areas, frontal and posterior, cortical and subcortical vis a vis acquired neuropathology, architectonic pathology, histometric differences and gene expression in order to test the hypothesis that particularly dorsal portions of the hemispheres are affected. We will also investigate the amygdala further to test the hypothesis that this nucleus is abnormal and that the limbic portions of this nucleus are

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particularly affected in WMS. Finally, we will begin to look at putative animal models by assaying GTF2I/IRD knock- outs anatomically and behaviorally. The results of these studies will help guide additional research aiming at looking at the steps between genomic lesion, messenger, and product expression leading to abnormal development in the WMS brain, and may shed additional light on normal brain and behavioral development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WILLIAMS CHARACTERIZATION

SYNDROME--MOLECULAR

GENETIC

Principal Investigator & Institution: Korenberg, Julie R.; Vice Chair for Research; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002 Summary: Understanding the molecular biological underpinnings of human behavior and cognition is a challenge to modern biomedicine for which Williams syndrome (WMS) provides a compelling model. We have characterized the genetic structure of WMS subjects to show the two common deletions are clustered, with one centromeric and two telomeric breakpoints and that the deleted region is flanked by complex unstable duplications that vary through primate evolution and are related to the instability in humans. By combing genetic with neurocognitive, neuroanatomic and neurophysiological measures in WMS with small deletions, the results parsed the genetic origins of WMS phenotypes, suggesting the following working hypotheses: that the deletion of two genes for transcription factors, GTF2I and GTF2IRD1 was linked to aspects of defective visual- spatial cognition including global processing, to aberrant neuroanatomy of the parieto-occipital region and the cerebellum, and to event related potential (ERP) measures of face processing; further, that this pathway was separated from that underlying the WMS larger superior temporal gyrus and correlational abnormal electrophysiological measures of language, both of which were associated with other regions. Combining these electrophysiological measures of language, both of which were associated with other regions. Combining these with other data supports a unifying hypothesis, that relates decreased expression of GTF2I/GTF2IRD1 to the differential impairment of the dorsal versus the ventral visual streams and related neural pathways, perhaps through the aberrant neuroanatomy observed. The experiments proposed are designed to test these hypotheses and to generate and test new working models relating the under-expression of specific genes deleted in WMS to specific neurocognitive features. 1. The clinical and molecular structures of 250 WMS subjects will be established and combined with the neurocognitive, ERP and neuroanatomic (MRI and fMRI) results from subprojects 0001, 0002, 0003. Analyses of subjects with the common and larger deletions as well as of eight rare subjects with small deletions, will be used to define, assign and test WMS neurocognitive phenotypes versus subsets of genes in the deleted region. 4. The expression of candidate genes GTF2I and GTFIRD1 will be evaluated during human brain morphogenesis and by the generation of knock-out mouse models. The results will help to elucidate the pathways that link genes with cognitive phenotypes and to formulate approaches for testing them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION

WILLIAMS

SYNDROME--NEUROANATOMICAL

Principal Investigator & Institution: Reiss, Allan L.; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099

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Williams Syndrome

Timing: Fiscal Year 2002 Summary: This application requests support for continuation of a highly productive scientific collaboration between Stanford University, The Salk Institute and other affiliated sites participating in this program project. Since the transfer of Project III to Stanford during the third year of the current project period, significant period, significant progress has been made in characterizing neuromorphological variation of the brain in WMS. In particular, analyses of structural neuroimaging data that, compared to normal controls, individuals with WMS have a unique profile of neuroanatomical variations with predisposition for particular volume and shape abnormalities. These include (1) reduced volume of posterior cerebral regions, (2) disproportionately reduced cerebral white matter volume, (3) disproportionately increased size of the cerebellum (including posterior vermis), superior temporal gyrus, right amygdala and superior temporal gyrus, and (4) abnormal cerebral and callosal shape as shown by 2D "bending angle" analysis. Further, pilot fMRI studies in four subjects confirm the feasibility of using this imaging modality in the WMS population and suggest that aberrant brain activation occurs in this condition. In view of these findings, new imaging studies are proposed to further explicate the neuroanatomical and neurofunctional profiles associated with WMS. These studies will elucidate, more precisely, the nature of variations in volume, shape and white matter integrity/connectivity of the WMS brain. Utilizing functional MRI, we also will directly investigate neural pathways underlying the WMS neurocognitive phenotype. The proposed imaging studies of WMS, within the context of this program project, provide an exceptional opportunity to examine critical associations among measures of cognition and behavior, neuroanatomy and brain function, and genetic influences. The results of this research, and their interpretation in parallel with related genetic, neurocognitive, neuropathological and electrophysiological data holds promise to reveal critical insights into bridging cognition and gene in WMS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: WILLIAMS CHARACTERIZATION

SYNDROME--NEUROPHYSIOLOGICAL

Principal Investigator & Institution: Mills, Debraen; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002 Summary: The purpose of this research continues to be to link variability in the phenotypic expression of specific patterns of a abnormally brain function in individuals with Williams Syndrome (WMS) to variability in brain structure and neurocognitive and genetic profiles as determined in the other projects of this program project. Previously we identified electrophysiological markers of abnormal brain function linked to the processing of faces and abnormal auditory language and sensory processing typical of individuals with WMS. We have begin to develop templates for each of these markers to characterize the variability in the patterns of brain activity across normal controls and individuals with WMS. In the proposed studies we will employ these templates along with modified diagnostic versions of the previous paradigms to assess the extent to which an individual with WMS fits the typical WMS pattern or may fall closer to the normal range. Variability in the expression of the phenotypic markers of brain function linked to specific cognitive functions will in turn be compared with concomitant variability in the genetic structural and neurocognitive profiles. Additionally, we have developed new paradigms to study brain function linked to differential activation of the dorsal and ventral visual streams perception and

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recognition of facial expressions, and language about spatial relations. We will record event-related potentials during these tasks using a high density array of 64 channels to increase the spatial distribution of our results. Behavioral and ERP data from these experiments will be compared with behavioral measures from standardized tests of language and cognitive capabilities. Variability in will also be compared with that individual's measurement of brain structure for the specific areas of the brain known to mediate that function, e.g. variability in the latency amplitude in the latency amplitude and distribution of ERPs linked to differential activation of the dorsal versus ventral visual streams will be compared with measurements of brain regions known to mediate dorsal versus ventral visual processing (in conjunction with subproject 0003), ERP indices of perception and recognition of facial expression will be compared with measures of the amygdala, which have been found to be abnormal in individuals with WMS. Moreover variability in the ERP patterns which have been found to be abnormal in individuals with WMS. Moreover variability in the ERP patterns elicited in the new studies and diagnostic paradigms described above will be compared with the presence or absence of specific genetic abnormalities typically observed in these individuals (in conjunction with subproject 0005). 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 “Williams syndrome” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Williams syndrome in the PubMed Central database: •

A family of chromatin remodeling factors related to Williams syndrome transcription factor. by Bochar DA, Savard J, Wang W, Lafleur DW, Moore P, Cote J, Shiekhattar R.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15513

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Generation and Comparative Analysis of [similar]3.3 Mb of Mouse Genomic Sequence Orthologous to the Region of Human Chromosome 7q11.23 Implicated in Williams Syndrome. by DeSilva U, Elnitski L, Idol JR, Doyle JL, Gan W, Thomas JW, Schwartz S, Dietrich NL, Beckstrom-Sternberg SM, McDowell JC, Blakesley RW, Bouffard GG, Thomas PJ, Touchman JW, Miller W, Green ED.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155257

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The role of a Williams-Beuren syndrome-associated helix --loop --helix domaincontaining transcription factor in activin/nodal signaling. by Ring C, Ogata S, Meek L, Song J, Ohta T, Miyazono K, Cho KW.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=186325

3 4

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

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

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

A 1943 children's book illustration showing Williams syndrome? Author(s): Oestreich AE. Source: Pediatric Radiology. 2002 August; 32(8): 610. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269254

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A case of Williams syndrome with a large, visible cytogenetic deletion. Author(s): Wu YQ, Nickerson E, Shaffer LG, Keppler-Noreuil K, Muilenburg A. Source: Journal of Medical Genetics. 1999 December; 36(12): 928-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636739

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A complete physical contig and partial transcript map of the Williams syndrome critical region. Author(s): Hockenhull EL, Carette MJ, Metcalfe K, Donnai D, Read AP, Tassabehji M. Source: Genomics. 1999 June 1; 58(2): 138-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10366445

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A componential view of theory of mind: evidence from Williams syndrome. Author(s): Tager-Flusberg H, Sullivan K. Source: Cognition. 2000 July 14; 76(1): 59-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10822043

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

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•

A family of chromatin remodeling factors related to Williams syndrome transcription factor. Author(s): Bochar DA, Savard J, Wang W, Lafleur DW, Moore P, Cote J, Shiekhattar R. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 February 1; 97(3): 1038-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10655480

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A gene-dosage PCR method for the detection of elastin gene deletions in patients with Williams syndrome. Author(s): del Rio T, Urban Z, Csiszar K, Boyd CD. Source: Clinical Genetics. 1998 August; 54(2): 129-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9761391

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A highly polymorphic CA/GT repeat (LIMK1GT) within the Williams syndrome critical region. Author(s): Mari A, Amati F, Conti E, Bengala M, Novelli G, Dallapiccola B. Source: Clinical Genetics. 1998 March; 53(3): 226-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9630081

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A longitudinal assessment of diverging verbal and non-verbal abilities in the Williams syndrome phenotype. Author(s): Jarrold C, Baddeley AD, Hewes AK, Phillips C. Source: Cortex. 2001 June; 37(3): 423-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485066

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A longitudinal study of cognitive abilities and educational attainment in Williams syndrome. Author(s): Udwin O, Davies M, Howlin P. Source: Developmental Medicine and Child Neurology. 1996 November; 38(11): 1020-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8913183

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A new clinical sign in Williams syndrome. Author(s): Withers S. Source: Archives of Disease in Childhood. 1996 July; 75(1): 89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8813883

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A novel human gene FKBP6 is deleted in Williams syndrome. Author(s): Meng X, Lu X, Morris CA, Keating MT. Source: Genomics. 1998 September 1; 52(2): 130-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9782077

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A novel human gene, WSTF, is deleted in Williams syndrome. Author(s): Lu X, Meng X, Morris CA, Keating MT. Source: Genomics. 1998 December 1; 54(2): 241-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9828126

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A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. Author(s): Wang YK, Samos CH, Peoples R, Perez-Jurado LA, Nusse R, Francke U. Source: Human Molecular Genetics. 1997 March; 6(3): 465-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9147651

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A study of relative clauses in Williams syndrome. Author(s): Grant J, Valian V, Karmiloff-Smith A. Source: Journal of Child Language. 2002 May; 29(2): 403-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109378

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A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome. Author(s): Tassabehji M, Carette M, Wilmot C, Donnai D, Read AP, Metcalfe K. Source: European Journal of Human Genetics : Ejhg. 1999 October-November; 7(7): 73747. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10573005

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Adaptive behavior of 4- through 8-year-old children with Williams syndrome. Author(s): Mervis CB, Klein-Tasman BP, Mastin ME. Source: Am J Ment Retard. 2001 January; 106(1): 82-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246716

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Adults with Williams syndrome. Author(s): Russell PS. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1998 September; 173: 268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9926109

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Adults with Williams syndrome. Author(s): Morris CA, Leonard CO, Dilts C, Demsey SA. Source: Am J Med Genet Suppl. 1990; 6: 102-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2118770

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Adults with Williams syndrome. Preliminary study of social, emotional and behavioural difficulties. Author(s): Davies M, Udwin O, Howlin P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1998 March; 172: 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614479

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American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Author(s): Committee on Genetics. Source: Pediatrics. 2001 May; 107(5): 1192-204. Erratum In: Pediatrics 2002 February; 109(2): 329. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11331709

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An investigation of verbal short-term memory and phonological processing in four children with Williams syndrome. Author(s): Majerus S, Barisnikov K, Vuillemin I, Poncelet M, van der Linden M. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2003 October; 9(5): 390-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972754

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Anaesthesia for MRI angiography in a patient with Williams syndrome. Author(s): Andrzejowski J, Mundy J. Source: Anaesthesia. 2000 January; 55(1): 97-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10594455

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Anaesthetic management of a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis. Author(s): Kawahito S, Kitahata H, Kimura H, Tanaka K, Sakai Y, Hirose Y, Oshita S. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1998 December; 45(12): 1203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10051941

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Analysis of cerebral shape in Williams syndrome. Author(s): Schmitt JE, Eliez S, Bellugi U, Reiss AL. Source: Archives of Neurology. 2001 February; 58(2): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176967

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Anesthesiologic problems in Williams syndrome: the CACNL2A locus is not involved. Author(s): Mammi I, Iles DE, Smeets D, Clementi M, Tenconi R. Source: Human Genetics. 1996 September; 98(3): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8707301

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Anxiety, fears, and phobias in persons with Williams syndrome. Author(s): Dykens EM. Source: Developmental Neuropsychology. 2003; 23(1-2): 291-316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730029

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Assessment of the influence of background noise on escape-maintained problem behavior and pain behavior in a child with Williams syndrome. Author(s): O'Reilly MF, Lacey C, Lancioni GE. Source: J Appl Behav Anal. 2000 Winter; 33(4): 511-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214027

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Attentional characteristics of infants and toddlers with Williams syndrome during triadic interactions. Author(s): Mervis CB, Morris CA, Klein-Tasman BP, Bertrand J, Kwitny S, Appelbaum LG, Rice CE. Source: Developmental Neuropsychology. 2003; 23(1-2): 243-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730027

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Audiovisual speech perception in Williams syndrome. Author(s): Bohning M, Campbell R, Karmiloff-Smith A. Source: Neuropsychologia. 2002; 40(8): 1396-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11931944

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Autism associated with Williams syndrome. Author(s): Reiss AL, Feinstein C, Rosenbaum KN, Borengasser-Caruso MA, Goldsmith BM. Source: The Journal of Pediatrics. 1985 February; 106(2): 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3968612

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Balloon dilation angioplasty of peripheral pulmonary stenosis associated with Williams syndrome. Author(s): Geggel RL, Gauvreau K, Lock JE. Source: Circulation. 2001 May 1; 103(17): 2165-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11331257

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Behavioral and emotional disturbance in individuals with Williams syndrome. Author(s): Einfeld SL, Tonge BJ, Florio T. Source: Am J Ment Retard. 1997 July; 102(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241407

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Bilateral vocal cord paralysis in Williams syndrome. Author(s): Stewart FJ, Dalzell M, McReid M, Cinnamond MJ. Source: Clinical Genetics. 1993 September; 44(3): 164-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8275577

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Block design performance in the Williams syndrome phenotype: a problem with mental imagery? Author(s): Farran EK, Jarrold C, Gathercole SE. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2001 September; 42(6): 719-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583244

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Body composition, energy expenditure, and energy intake in patients with Williams syndrome. Author(s): Kaplan AS, Stallings VA, Zemel BS, Green KA, Kaplan P. Source: The Journal of Pediatrics. 1998 February; 132(2): 223-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9506631

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Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? Author(s): Chang L, Ernst T, Berman N. Source: Neurology. 1999 March 10; 52(4): 898-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078767

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Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? Author(s): Rae C, Karmiloff-Smith A, Lee MA, Dixon RM, Grant J, Blamire AM, Thompson CH, Styles P, Radda GK. Source: Neurology. 1998 July; 51(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9674775

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Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome. Author(s): Bellugi U, Lichtenberger L, Mills D, Galaburda A, Korenberg JR. Source: Trends in Neurosciences. 1999 May; 22(5): 197-207. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10322491

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Brief report: four case histories and a literature review of Williams syndrome and autistic behavior. Author(s): Gillberg C, Rasmussen P. Source: Journal of Autism and Developmental Disorders. 1994 June; 24(3): 381-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8050990

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Brief report: response to methylphenidate in two children with Williams syndrome. Author(s): Power TJ, Blum NJ, Jones SM, Kaplan PE. Source: Journal of Autism and Developmental Disorders. 1997 February; 27(1): 79-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018583

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Can adolescents with Williams syndrome tell the difference between lies and jokes? Author(s): Sullivan K, Winner E, Tager-Flusberg H. Source: Developmental Neuropsychology. 2003; 23(1-2): 85-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730021

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Cardiovascular manifestations in 75 patients with Williams syndrome. Author(s): Eronen M, Peippo M, Hiippala A, Raatikka M, Arvio M, Johansson R, Kahkonen M. Source: Journal of Medical Genetics. 2002 August; 39(8): 554-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161592

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Carotid ultrasound examination in Williams syndrome. Author(s): Sadler LS, Gingell R, Martin DJ. Source: The Journal of Pediatrics. 1998 February; 132(2): 354-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9506657

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Central precocious puberty in girls with Williams syndrome. Author(s): Partsch CJ, Japing I, Siebert R, Gosch A, Wessel A, Sippell WG, Pankau R. Source: The Journal of Pediatrics. 2002 September; 141(3): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12219071

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Cerebellar abnormalities in infants and toddlers with Williams syndrome. Author(s): Jones W, Hesselink J, Courchesne E, Duncan T, Matsuda K, Bellugi U. Source: Developmental Medicine and Child Neurology. 2002 October; 44(10): 688-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12418794

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Cerebral artery stenoses in Williams syndrome cause strokes in childhood. Author(s): Kaplan P, Levinson M, Kaplan BS. Source: The Journal of Pediatrics. 1995 June; 126(6): 943-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7776101

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Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome. Author(s): Ardinger RH Jr, Goertz KK, Mattioli LF. Source: American Journal of Medical Genetics. 1994 July 1; 51(3): 200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8074144

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Chiari I malformation in asymptomatic young children with Williams syndrome: clinical and MRI study. Author(s): Mercuri E, Atkinson J, Braddick O, Rutherford MA, Cowan FM, Counsell SJ, Dubowitz LM, Bydder G. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1997; 1(5-6): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728215

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Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome. Author(s): Brewer CM, Morrison N, Tolmie JL. Source: Archives of Disease in Childhood. 1996 January; 74(1): 59-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8660051

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Coeliac disease in Williams syndrome. Author(s): Giannotti A, Tiberio G, Castro M, Virgilii F, Colistro F, Ferretti F, Digilio MC, Gambarara M, Dallapiccola B. Source: Journal of Medical Genetics. 2001 November; 38(11): 767-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694549

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Cognitive dissection of Williams syndrome. Author(s): Wang PP. Source: American Journal of Medical Genetics. 1999 February 5; 88(1): 103-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10050977

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Cognitive functioning in adults with Williams syndrome. Author(s): Howlin P, Davies M, Udwin O. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1998 February; 39(2): 183-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9669231

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Cognitive, adaptive, and behavioral characteristics of Williams syndrome. Author(s): Greer MK, Brown FR 3rd, Pai GS, Choudry SH, Klein AJ. Source: American Journal of Medical Genetics. 1997 September 19; 74(5): 521-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342204

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Cognitive, lexical and morpho-syntactic profiles of Israeli children with Williams syndrome. Author(s): Levy Y, Bechar T. Source: Cortex. 2003 April; 39(2): 255-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784888

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Community care for adults with Williams syndrome: how families cope and the availability of support networks. Author(s): Udwin O, Howlin P, Davies M, Mannion E. Source: Journal of Intellectual Disability Research : Jidr. 1998 June; 42 ( Pt 3): 238-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678408

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Comparative genomic sequence analysis of the Williams syndrome region (LIMK1RFC2) of human chromosome 7q11.23. Author(s): Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. 2000 October; 11(10): 890-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11003705

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Comparative mapping of the region of human chromosome 7 deleted in Williams syndrome. Author(s): DeSilva U, Massa H, Trask BJ, Green ED. Source: Genome Research. 1999 May; 9(5): 428-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10330122

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Complete augmentation of diffuse narrowing of the aorta with Williams syndrome by using an overturn approach. Author(s): Yamagishi M, Shuntoh K, Matsushita T, Fujiwara K, Shinkawa T, Miyazaki T, Kitamura N. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 June; 125(6): 1556-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830088

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Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes. Author(s): Meng X, Lu X, Li Z, Green ED, Massa H, Trask BJ, Morris CA, Keating MT. Source: Human Genetics. 1998 November; 103(5): 590-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9860302

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Composite aortoplasty for recurrent coarctation after neonatal repair in Williams syndrome. Author(s): Marks JL, Mitchell MB, Campbell DN, Toews WH. Source: The Annals of Thoracic Surgery. 2004 January; 77(1): 319-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726089

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Concomitant reentrant tachycardias from concealed accessory atrioventricular bypass tract and atrioventricular nodal reentry in a patient with Williams syndrome. Author(s): Kantharia BK, Mittleman RS. Source: Cardiology. 1999; 91(4): 264-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10545683

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Configural and local processing of faces in children with Williams syndrome. Author(s): Deruelle C, Mancini J, Livet MO, Casse-Perrot C, de Schonen S. Source: Brain and Cognition. 1999 December; 41(3): 276-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10585239

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Contractures in patients with Williams syndrome. Author(s): Kaplan P, Kirschner M, Watters G, Costa MT. Source: Pediatrics. 1989 November; 84(5): 895-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2797983

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Coronary artery disease and anesthesia-related death in children with Williams syndrome. Author(s): Horowitz PE, Akhtar S, Wulff JA, Al Fadley F, Al Halees Z. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2002 December; 16(6): 73941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12486657

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Corpus callosum morphology of Williams syndrome: relation to genetics and behavior. Author(s): Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL. Source: Developmental Medicine and Child Neurology. 2001 March; 43(3): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11263684

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Cytogenetic testing for Williams syndrome. Author(s): Jalal SM, Crifasi PA, Karnes PS, Michels VV. Source: Mayo Clinic Proceedings. 1996 January; 71(1): 67-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8538237

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De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome. Author(s): von Dadelszen P, Chitayat D, Winsor EJ, Cohen H, MacDonald C, Taylor G, Rose T, Hornberger LK. Source: American Journal of Medical Genetics. 2000 February 14; 90(4): 270-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710222

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Delay in diagnosis of Williams syndrome. Author(s): Huang L, Sadler L, O'Riordan MA, Robin NH. Source: Clinical Pediatrics. 2002 May; 41(4): 257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12041723

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Deletions at chromosome regions 7q11.23 and 7q36 in a patient with Williams syndrome. Author(s): Wouters CH, Meijers-Heijboer HJ, Eussen BJ, van der Heide AA, van Luijk RB, van Drunen E, Beverloo BB, Visscher F, Van Hemel JO. Source: American Journal of Medical Genetics. 2001 August 15; 102(3): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484204

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Delineation of the common critical region in Williams syndrome and clinical correlation of growth, heart defects, ethnicity, and parental origin. Author(s): Wu YQ, Sutton VR, Nickerson E, Lupski JR, Potocki L, Korenberg JR, Greenberg F, Tassabehji M, Shaffer LG. Source: American Journal of Medical Genetics. 1998 June 16; 78(1): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9637430

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Demonstration of supravalvar aortic stenosis by different cardiac imaging modalities in Williams syndrome. Author(s): Youn HJ, Chung WS, Hong SJ. Source: Heart (British Cardiac Society). 2002 October; 88(4): 438. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12231615

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Dental anomalies in Williams syndrome. Author(s): Kashyap AS, Sharma HS, Kumar P. Source: Postgraduate Medical Journal. 2000 November; 76(901): 712. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11060148

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Dental characteristics in Williams syndrome: a clinical and radiographic evaluation. Author(s): Axelsson S, Bjornland T, Kjaer I, Heiberg A, Storhaug K. Source: Acta Odontologica Scandinavica. 2003 June; 61(3): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868685

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Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Author(s): Botta A, Novelli G, Mari A, Novelli A, Sabani M, Korenberg J, Osborne LR, Digilio MC, Giannotti A, Dallapiccola B. Source: Journal of Medical Genetics. 1999 June; 36(6): 478-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10874638

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Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome. Author(s): Karmiloff-Smith A, Brown JH, Grice S, Paterson S. Source: Developmental Neuropsychology. 2003; 23(1-2): 227-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730026

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Differences by sex in cardiovascular disease in Williams syndrome. Author(s): Sadler LS, Pober BR, Grandinetti A, Scheiber D, Fekete G, Sharma AN, Urban Z. Source: The Journal of Pediatrics. 2001 December; 139(6): 849-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743512

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Difficulty in writing Japanese semantic characters in a 9-year-old boy with Williams syndrome. Author(s): Nakamura M, Hara K, Watamaki T, Nishimura B, Kumagai T, Matsumoto A, Miura K, Yamanaka T, Hayakawa C, Miyazaki S. Source: Journal of Intellectual Disability Research : Jidr. 1999 December; 43 ( Pt 6): 562-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622373

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Disordered visual processing and oscillatory brain activity in autism and Williams syndrome. Author(s): Grice SJ, Spratling MW, Karmiloff-Smith A, Halit H, Csibra G, de Haan M, Johnson MH. Source: Neuroreport. 2001 August 28; 12(12): 2697-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522950

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Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness. Author(s): Lacolley P, Boutouyrie P, Glukhova M, Daniel Lamaziere JM, Plouin PF, Bruneval P, Vuong P, Corvol P, Laurent S. Source: Clinical Science (London, England : 1979). 2002 July; 103(1): 21-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12095400

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Distinctive personality characteristics of 8-, 9-, and 10-year-olds with Williams syndrome. Author(s): Klein-Tasman BP, Mervis CB. Source: Developmental Neuropsychology. 2003; 23(1-2): 269-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730028

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Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome. Author(s): Doyle JL, DeSilva U, Miller W, Green ED. Source: Cytogenetics and Cell Genetics. 2000; 90(3-4): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124535

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Divided attention, selective attention and drawing: processing preferences in Williams syndrome are dependent on the task administered. Author(s): Farran EK, Jarrold C, Gathercole SE. Source: Neuropsychologia. 2003; 41(6): 676-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591025

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Do individuals with Williams syndrome have bizarre semantics? Evidence for lexical organization using an on-line task. Author(s): Tyler LK, Karmiloff-Smith A, Voice JK, Stevens T, Grant J, Udwin O, Davies M, Howlin P. Source: Cortex. 1997 September; 33(3): 515-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9339332

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Dorsal forebrain anomaly in Williams syndrome. Author(s): Galaburda AM, Schmitt JE, Atlas SW, Eliez S, Bellugi U, Reiss AL. Source: Archives of Neurology. 2001 November; 58(11): 1865-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11708996

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Drawing abilities in Williams syndrome: a case study. Author(s): Stiles J, Sabbadini L, Capirci O, Volterra V. Source: Developmental Neuropsychology. 2000; 18(2): 213-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280965

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Drawings by individuals with Williams syndrome: are people different from shapes? Author(s): Dykens EM, Rosner BA, Ly TM. Source: Am J Ment Retard. 2001 January; 106(1): 94-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246717

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Early categorization abilities in young children with Williams syndrome. Author(s): Nazzi T, Karmiloff-Smith A. Source: Neuroreport. 2002 July 19; 13(10): 1259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151782

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Early development (5 to 48 months) in Williams syndrome. A study of 14 children. Author(s): Plissart L, Fryns JP. Source: Genet Couns. 1999; 10(2): 151-6. Erratum In: Genet Couns 2000; 11(1): 83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10422008

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Early development of children with Williams syndrome. Author(s): Sarimski K. Source: Genet Couns. 1999; 10(2): 141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10422007

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Early linguistic abilities of Italian children with Williams syndrome. Author(s): Volterra V, Caselli MC, Capirci O, Tonucci F, Vicari S. Source: Developmental Neuropsychology. 2003; 23(1-2): 33-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730019

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Early puberty in Williams syndrome. Author(s): Cherniske EM, Sadler LS, Schwartz D, Carpenter TO, Pober BR. Source: Clinical Dysmorphology. 1999 April; 8(2): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319200

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Echocardiographic and Doppler findings in the Williams syndrome. Author(s): Brand A, Keren A, Reifen RM, Gross-Kieselstein E, Armir N. Source: The American Journal of Cardiology. 1989 March 1; 63(9): 633-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2645763

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Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype. Author(s): Urban Z, Peyrol S, Plauchu H, Zabot MT, Lebwohl M, Schilling K, Green M, Boyd CD, Csiszar K. Source: Pediatric Dermatology. 2000 January-February; 17(1): 12-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10720981

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Elastin gene deletions in Williams syndrome. Author(s): Smoot LB. Source: Current Opinion in Pediatrics. 1995 December; 7(6): 698-701. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8776022

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Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome. Author(s): Girard A, Sidi D, Aggoun Y, Laude D, Bonnet D, Elghozi JL. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 April; 12(2): 72-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102453

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Elastin region deletions in Williams syndrome. Author(s): Zhang J, Kumar A, Roux K, Williams CA, Wallace MR. Source: Genetic Testing. 1999; 3(4): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10627943

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Elevated 1,25-dihydroxyvitamin D and normocalcaemia in presumed familial Williams syndrome. Author(s): Knudtzon J, Aksnes L, Akslen LA, Aarskog D. Source: Clinical Genetics. 1987 December; 32(6): 369-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3436085

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Elevated ambulatory blood pressure in 20 subjects with Williams syndrome. Author(s): Broder K, Reinhardt E, Ahern J, Lifton R, Tamborlane W, Pober B. Source: American Journal of Medical Genetics. 1999 April 23; 83(5): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10232742

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Enlarged cerebellar vermis in Williams syndrome. Author(s): Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL. Source: Journal of Psychiatric Research. 2001 July-August; 35(4): 225-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11578640

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ERP abnormalities of illusory contour perception in Williams syndrome. Author(s): Grice SJ, Haan MD, Halit H, Johnson MH, Csibra G, Grant J, Karmiloff-Smith A. Source: Neuroreport. 2003 October 6; 14(14): 1773-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534418

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Evaluation of arterial stiffness in children with Williams syndrome: Does it play a role in evolving hypertension? Author(s): Salaymeh KJ, Banerjee A. Source: American Heart Journal. 2001 September; 142(3): 549-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526372

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Exercise testing and 24-hour ambulatory blood pressure monitoring in children with Williams syndrome. Author(s): Giordano U, Turchetta A, Giannotti A, Digilio MC, Virgilii F, Calzolari A. Source: Pediatric Cardiology. 2001 November-December; 22(6): 509-11. Epub 2001 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11894156

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Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome. Author(s): Botta A, Sangiuolo F, Calza L, Giardino L, Potenza S, Novelli G, Dallapiccola B. Source: Genomics. 1999 December 15; 62(3): 525-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10644452

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Expressive language of children with Williams syndrome. Author(s): Udwin O, Yule W. Source: Am J Med Genet Suppl. 1990; 6: 108-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2118771

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Expressive vocabulary ability of toddlers with Williams syndrome or Down syndrome: a comparison. Author(s): Mervis CB, Robinson BF. Source: Developmental Neuropsychology. 2000; 17(1): 111-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10916578

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Extended aortic and left main coronary angioplasty with a single pericardial patch in a patient with Williams syndrome. Author(s): Matsuda H, Miyamoto Y, Takahashi T, Kadoba K, Nakano S, Sano T. Source: The Annals of Thoracic Surgery. 1991 December; 52(6): 1331-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1755690

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Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation. Author(s): Paul BM, Stiles J, Passarotti A, Bavar N, Bellugi U. Source: Neuroreport. 2002 July 2; 13(9): 1115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151752

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Facial and dental appearance of Williams syndrome. Author(s): Tarjan I, Balaton G, Balaton P, Varbiro S, Vajo Z. Source: Postgraduate Medical Journal. 2003 April; 79(930): 241. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743349

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Facial expression recognition in Williams syndrome. Author(s): Gagliardi C, Frigerio E, Burt DM, Cazzaniga I, Perrett DI, Borgatti R. Source: Neuropsychologia. 2003; 41(6): 733-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591030

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Familial occurrence of the Williams syndrome. Author(s): White RA, Preus M, Watters GV, Fraser FC. Source: The Journal of Pediatrics. 1977 October; 91(4): 614-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=908984

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Familial Williams syndrome. Author(s): Cortada X, Taysi K, Hartmann AF. Source: Clinical Genetics. 1980 September; 18(3): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7192194

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Family contexts, parental behaviour, and personality profiles of children and adolescents with Prader-Willi, fragile-X, or Williams syndrome. Author(s): van Lieshout CF, De Meyer RE, Curfs LM, Fryns JP. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1998 July; 39(5): 699-710. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9690933

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FISH analysis in patients with clinical diagnosis of Williams syndrome. Author(s): Elcioglu N, Mackie-Ogilvie C, Daker M, Berry AC. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 January; 87(1): 48-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9510447

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Generalized arteriopathy in Williams syndrome: an intravascular ultrasound study. Author(s): Rein AJ, Preminger TJ, Perry SB, Lock JE, Sanders SP. Source: Journal of the American College of Cardiology. 1993 June; 21(7): 1727-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8496544

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Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome. Author(s): DeSilva U, Elnitski L, Idol JR, Doyle JL, Gan W, Thomas JW, Schwartz S, Dietrich NL, Beckstrom-Sternberg SM, McDowell JC, Blakesley RW, Bouffard GG, Thomas PJ, Touchman JW, Miller W, Green ED. Source: Genome Research. 2002 January; 12(1): 3-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11779826

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Genetic approaches to cardiovascular disease. Supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. Author(s): Keating MT. Source: Circulation. 1995 July 1; 92(1): 142-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7788908

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Genetically dissociated components of working memory: evidence from Down's and Williams syndrome. Author(s): Jarrold C, Baddeley AD, Hewes AK. Source: Neuropsychologia. 1999 June; 37(6): 637-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10390025

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Genetics of childhood disorders: XXVI. Williams syndrome and brain-behavior relationships. Author(s): Schultz RT, Grelotti DJ, Pober B. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 May; 40(5): 606-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349707

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Genetics of childhood disorders: XXVII. Genes and cognition in Williams syndrome. Author(s): Osborne L, Pober B. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 June; 40(6): 732-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11392353

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Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Author(s): Bayarsaihan D, Dunai J, Greally JM, Kawasaki K, Sumiyama K, Enkhmandakh B, Shimizu N, Ruddle FH. Source: Genomics. 2002 January; 79(1): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11827466

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Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome. Author(s): Castorina P, Selicorni A, Bedeschi F, Dalpra L, Larizza L. Source: American Journal of Medical Genetics. 1997 March 3; 69(1): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9066894

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Growth of the aorta in children with Williams syndrome: does surgery make a difference? Author(s): English RF, Colan SD, Kanani PM, Ettedgui JA. Source: Pediatric Cardiology. 2003 November-December; 24(6): 566-8. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14758447

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Heat shock protein 27 gene: chromosomal and molecular location and relationship to Williams syndrome. Author(s): Stock AD, Spallone PA, Dennis TR, Netski D, Morris CA, Mervis CB, Hobart HH. Source: American Journal of Medical Genetics. 2003 July 30; 120A(3): 320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838549

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Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Author(s): Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating MT. Source: Nature Genetics. 1993 September; 5(1): 11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7693128

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Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with Williams syndrome. Author(s): Nakayama T, Matsuoka R, Kimura M, Hirota H, Mikoshiba K, Shimizu Y, Shimizu N, Akagawa K. Source: Cytogenetics and Cell Genetics. 1998; 82(1-2): 49-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9763659

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Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome. Author(s): Osborne LR, Soder S, Shi XM, Pober B, Costa T, Scherer SW, Tsui LC. Source: American Journal of Human Genetics. 1997 August; 61(2): 449-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9311751

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How common is precocious puberty in patients with Williams syndrome? Author(s): Scothorn DJ, Butler MG. Source: Clinical Dysmorphology. 1997 January; 6(1): 91-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018426

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Human genetics: dissecting Williams syndrome. Author(s): Monaco AP. Source: Current Biology : Cb. 1996 November 1; 6(11): 1396-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8939595

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Hyperacusis and otitis media in individuals with Williams syndrome. Author(s): Klein AJ, Armstrong BL, Greer MK, Brown FR 3rd. Source: J Speech Hear Disord. 1990 May; 55(2): 339-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2329796

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Hyperacusis and Williams syndrome. Author(s): Nigam A, Samuel PR. Source: The Journal of Laryngology and Otology. 1994 June; 108(6): 494-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027650

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Hyperacusis in Williams syndrome. Author(s): Johnson LB, Comeau M, Clarke KD. Source: The Journal of Otolaryngology. 2001 April; 30(2): 90-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11770962

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Hyperacusis in Williams syndrome: a sample survey study. Author(s): Van Borsel J, Curfs LM, Fryns JP. Source: Genet Couns. 1997; 8(2): 121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9219010

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Hypercalcemic phase of Williams syndrome. Author(s): Bzduch V. Source: The Journal of Pediatrics. 1993 September; 123(3): 496. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8355137

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Hypothesis for development of a behavioral phenotype in Williams syndrome. Author(s): Dilts CV, Morris CA, Leonard CO. Source: Am J Med Genet Suppl. 1990; 6: 126-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2118772

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I. The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. Author(s): Bellugi U, Lichtenberger L, Jones W, Lai Z, St George M. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 7-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953231

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Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. Author(s): Osborne LR, Martindale D, Scherer SW, Shi XM, Huizenga J, Heng HH, Costa T, Pober B, Lew L, Brinkman J, Rommens J, Koop B, Tsui LC. Source: Genomics. 1996 September 1; 36(2): 328-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8812460

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II. Hypersociability in Williams Syndrome. Author(s): Jones W, Bellugi U, Lai Z, Chiles M, Reilly J, Lincoln A, Adolphs R. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 30-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953232

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III. Electrophysiological studies of face processing in Williams syndrome. Author(s): Mills DL, Alvarez TD, St George M, Appelbaum LG, Bellugi U, Neville H. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 47-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953233

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Imparied calcitonin secretion in patients with Williams syndrome. Author(s): Culler FL, Jones KL, Deftos LJ. Source: The Journal of Pediatrics. 1985 November; 107(5): 720-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4056970

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Implicit learning in children and adults with Williams syndrome. Author(s): Don AJ, Schellenberg EG, Reber AS, DiGirolamo KM, Wang PP. Source: Developmental Neuropsychology. 2003; 23(1-2): 201-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730025

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Implicit versus explicit memory function in children with Down and Williams syndrome. Author(s): Vicari S. Source: Downs Syndr Res Pract. 2001 October; 7(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706810

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Increased gyrification in Williams syndrome: evidence using 3D MRI methods. Author(s): Schmitt JE, Watts K, Eliez S, Bellugi U, Galaburda AM, Reiss AL. Source: Developmental Medicine and Child Neurology. 2002 May; 44(5): 292-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12033713

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Increased prevalence of urinary symptoms and voiding dysfunction in Williams syndrome. Author(s): Schulman SL, Zderic S, Kaplan P. Source: The Journal of Pediatrics. 1996 September; 129(3): 466-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8804343

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Increased renal medullary echogenicity in patients with Williams syndrome. Author(s): Cote G, Jequier S, Kaplan P. Source: Pediatric Radiology. 1989; 19(6-7): 481-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2671904

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Independence and adaptive behavior in adults with Williams syndrome. Author(s): Davies M, Howlin P, Udwin O. Source: American Journal of Medical Genetics. 1997 May 16; 70(2): 188-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9128941

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Infantile spasms in a patient with Williams syndrome and craniosynostosis. Author(s): Morimoto M, An B, Ogami A, Shin N, Sugino Y, Sawai Y, Usuku T, Tanaka M, Hirai K, Nishimura A, Hasegawa K, Sugimoto T. Source: Epilepsia. 2003 November; 44(11): 1459-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636357

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Infantile spasms in two children with Williams syndrome. Author(s): Tsao CY, Westman JA. Source: American Journal of Medical Genetics. 1997 July 11; 71(1): 54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215769

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Inflectional morphology in German Williams syndrome. Author(s): Krause M, Penke M. Source: Brain and Cognition. 2002 March-April; 48(2-3): 410-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030478

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Intact perception of biological motion in the face of profound spatial deficits: Williams syndrome. Author(s): Jordan H, Reiss JE, Hoffman JE, Landau B. Source: Psychological Science : a Journal of the American Psychological Society / Aps. 2002 March; 13(2): 162-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11934001

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Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms. Author(s): Mizugishi K, Yamanaka K, Kuwajima K, Kondo I. Source: Journal of Human Genetics. 1998; 43(3): 178-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9747030

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Interstitial deletion of the long arm of chromosome 6(q22.2q23) in a boy with phenotypic features of Williams syndrome. Author(s): Bzduch V, Lukacova M. Source: Clinical Genetics. 1989 March; 35(3): 230-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2706804

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Intrauterine hypercalcaemia and non-immune hydrops fetalis--relationship to the Williams syndrome. Author(s): Westgren M, Eastham WN, Ghandourah S, Woodhouse N. Source: Prenatal Diagnosis. 1988 June; 8(5): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3405972

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Ischemic stroke and intracranial multifocal cerebral arteriopathy in Williams syndrome. Author(s): Soper R, Chaloupka JC, Fayad PB, Greally JM, Shaywitz BA, Awad IA, Pober BR. Source: The Journal of Pediatrics. 1995 June; 126(6): 945-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7776102

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IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study. Author(s): Reiss AL, Eliez S, Schmitt JE, Straus E, Lai Z, Jones W, Bellugi U. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 65-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953234

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Knowledge enrichment and conceptual change in folkbiology: evidence from Williams syndrome. Author(s): Johnson SC, Carey S. Source: Cognitive Psychology. 1998 November; 37(2): 156-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9878105

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Kyphoscoliosis in Williams syndrome. Author(s): Osebold WR, King HA. Source: Spine. 1994 February 1; 19(3): 367-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7513444

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Language and cognition in two children with Williams syndrome. Author(s): Thal D, Bates E, Bellugi U. Source: Journal of Speech and Hearing Research. 1989 September; 32(3): 489-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2476586

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Language and conversational abilities in Williams syndrome: how good is good? Author(s): Stojanovik V, Perkins M, Howard S. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. 2001; 36 Suppl: 234-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11340788

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Language and Williams syndrome: how intact is “intact”? Author(s): Karmiloff-Smith A, Grant J, Berthoud I, Davies M, Howlin P, Udwin O. Source: Child Development. 1997 April; 68(2): 246-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9180000

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Language, speech and hearing in Williams syndrome: intervention approaches and research needs. Author(s): Meyerson MD, Frank RA. Source: Developmental Medicine and Child Neurology. 1987 April; 29(2): 258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3582796

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Large mirror movements of upper extremities in Williams syndrome. Author(s): Glos J, Bzduch V, Lisy L, Jariabkova K. Source: Pediatric Neurology. 1993 September-October; 9(5): 414. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8292223

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Learning to read in Williams syndrome: looking beneath the surface of atypical reading development. Author(s): Laing E, Hulme C, Grant J, Karmiloff-Smith A. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2001 September; 42(6): 729-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583245

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Lexical production in children with Williams syndrome: spontaneous use of gesture in a naming task. Author(s): Bello A, Capirci O, Volterra V. Source: Neuropsychologia. 2004; 42(2): 201-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644106

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LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Author(s): Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 2004 February; 26(2): 141-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745832

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LIM-kinase deleted in Williams syndrome. Author(s): Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Proschel C, Gutowski NJ, Mao X, Sheer D. Source: Nature Genetics. 1996 July; 13(3): 272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8673124

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Linguistic abilities in Italian children with Williams syndrome. Author(s): Volterra V, Capirci O, Pezzini G, Sabbadini L, Vicari S. Source: Cortex. 1996 December; 32(4): 663-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8954245

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Linguistic dissociations in Williams syndrome: evaluating receptive syntax in on-line and off-line tasks. Author(s): Karmiloff-Smith A, Tyler LK, Voice K, Sims K, Udwin O, Howlin P, Davies M. Source: Neuropsychologia. 1998 April; 36(4): 343-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9665645

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Longitudinal course of behavioral and emotional problems in Williams syndrome. Author(s): Einfeld SL, Tonge BJ, Rees VW. Source: Am J Ment Retard. 2001 January; 106(1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246715

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Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. Author(s): Partsch CJ, Dreyer G, Gosch A, Winter M, Schneppenheim R, Wessel A, Pankau R. Source: The Journal of Pediatrics. 1999 January; 134(1): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9880454

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Low MSAFP levels and Williams syndrome. Author(s): Chodirker BN, Greenberg CR, Giddins NG, Dawson AJ, Evans JA, Chudley AE. Source: American Journal of Medical Genetics. 1997 November 12; 72(4): 448-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9375729

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Masseter spasm in Williams syndrome. Author(s): Matthews AJ, Vernon JM. Source: Anaesthesia. 1991 August; 46(8): 706. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1888003

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Mechanical properties of the common carotid artery in Williams syndrome. Author(s): Aggoun Y, Sidi D, Levy BI, Lyonnet S, Kachaner J, Bonnet D. Source: Heart (British Cardiac Society). 2000 September; 84(3): 290-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10956293

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Medial telangiectatic sacral nevi (Types A and C) associated with Williams syndrome. Author(s): Schepis C, Greco D, Bosco P, Ragusa A, Romano C. Source: Dermatology (Basel, Switzerland). 2000; 201(3): 285-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096215

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Memory abilities in children with Williams syndrome. Author(s): Vicari S, Brizzolara D, Carlesimo GA, Pezzini G, Volterra V. Source: Cortex. 1996 September; 32(3): 503-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8886525

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Metacarpophalangeal pattern profile analysis in Williams syndrome. Author(s): Burns MA, McLeod DR, Linton LR, Butler MG. Source: American Journal of Medical Genetics. 1993 September 15; 47(4): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8256807

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Micro-deletion detected by fluorescent in situ hybridization for Williams syndrome. Author(s): Dewan K, Borgaonkar DS, Bartoshesky LE, Tuttle D. Source: Del Med J. 1999 November; 71(11): 467-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10615798

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Microdeletion oe chromosomal region 7Q11.23 in Williams syndrome. Author(s): Hou JW, Wang JK, Wang TR. Source: J Formos Med Assoc. 1997 February; 96(2): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9071842

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Mitral regurgitation without supravalvular aortic stenosis in Williams syndrome. Author(s): Takagi H, Mori Y, Iwata H, Umeda Y, Fukumoto Y, Matsuno Y, Matsutomo M, Shimokawa K, Nishigaki K, Fujiwara H, Hirose H. Source: Heart and Vessels. 2002 September; 16(6): 257-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382035

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Molecular cytogenetic diagnosis of Williams syndrome. Author(s): Hirota H, Matsuoka R, Kimura M, Imamura S, Joh-o K, Ando M, Takao A, Momma K. Source: American Journal of Medical Genetics. 1996 August 23; 64(3): 473-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8862624

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Molecular definition of the chromosome 7 deletion in Williams syndrome and parentof-origin effects on growth. Author(s): Perez Jurado LA, Peoples R, Kaplan P, Hamel BC, Francke U. Source: American Journal of Human Genetics. 1996 October; 59(4): 781-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8808592

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Morphological abilities of Hebrew-speaking adolescents with Williams syndrome. Author(s): Levy Y, Hermon S. Source: Developmental Neuropsychology. 2003; 23(1-2): 59-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730020

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Morphological patterns in Hungarian children with Williams syndrome and the rule debates. Author(s): Pleh C, Lukacs A, Racsmany M. Source: Brain and Language. 2003 September; 86(3): 377-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972368

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Morphology and morphometry of the corpus callosum in Williams syndrome: a T1weighted MRI study. Author(s): Tomaiuolo F, Di Paola M, Caravale B, Vicari S, Petrides M, Caltagirone C. Source: Neuroreport. 2002 December 3; 13(17): 2281-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488811

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Mucinous cystadenoma of ovary in a patient with Williams syndrome. Author(s): Marles SL, Goldberg NA, Chudley AE. Source: American Journal of Medical Genetics. 1993 May 15; 46(3): 349. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8488885

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Multifocal intracranial occlusive vasculopathy resulting in stroke: an unusual manifestation of Williams syndrome. Author(s): Putman CM, Chaloupka JC, Eklund JE, Fulbright RK. Source: Ajnr. American Journal of Neuroradiology. 1995 August; 16(7): 1536-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7484650

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Myocardial infarction leading to sudden death in the Williams syndrome: report of three cases. Author(s): Conway EE Jr, Noonan J, Marion RW, Steeg CN. Source: The Journal of Pediatrics. 1990 October; 117(4): 593-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2213386

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Natural history of Williams syndrome: physical characteristics. Author(s): Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL. Source: The Journal of Pediatrics. 1988 August; 113(2): 318-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2456379

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Neonatal Williams syndrome presenting as an isolated supravalvular pulmonary stenosis. Author(s): di Gioia CR, Ciallella C, d'Amati G, Parroni E, Nardone AM, Gallo P. Source: Archives of Pathology & Laboratory Medicine. 2003 September; 127(9): E367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946215

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Neural correlates of auditory perception in Williams syndrome: an fMRI study. Author(s): Levitin DJ, Menon V, Schmitt JE, Eliez S, White CD, Glover GH, Kadis J, Korenberg JR, Bellugi U, Reiss AL. Source: Neuroimage. 2003 January; 18(1): 74-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507445

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Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function. Author(s): Atkinson J, Braddick O, Anker S, Curran W, Andrew R, Wattam-Bell J, Braddick F. Source: Developmental Neuropsychology. 2003; 23(1-2): 139-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730023

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Neurologic findings in children and adults with Williams syndrome. Author(s): Chapman CA, du Plessis A, Pober BR. Source: Journal of Child Neurology. 1996 January; 11(1): 63-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8745391

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Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome. Author(s): Bellugi U, Bihrle A, Jernigan T, Trauner D, Doherty S. Source: Am J Med Genet Suppl. 1990; 6: 115-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2144426

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Objects, motions, and paths: spatial language in children with Williams syndrome. Author(s): Landau B, Zukowski A. Source: Developmental Neuropsychology. 2003; 23(1-2): 105-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730022

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Occurrence of an astrocytoma in a patient with Williams syndrome. Author(s): Semmekrot BA, Rotteveel JJ, Bakker-Niezen SH, Logt F. Source: Pediatr Neurosci. 1985-86; 12(3): 188-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3843262

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Occurrence of non-Hodgkin's lymphoma in Williams syndrome--case report. Author(s): Felice PV, Ritter SD, Anto J. Source: Angiology. 1994 February; 45(2): 167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8129194

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Oligoyric microcephaly in a child with Williams syndrome. Author(s): Faravelli F, D'Arrigo S, Bagnasco I, Selicorni A, D'Incerti L, Riva D, Pantaleoni C. Source: American Journal of Medical Genetics. 2003 March 1; 117A(2): 169-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567416

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On the trail of genetic culprits in Williams syndrome. Author(s): Keating MT. Source: Cardiovascular Research. 1997 November; 36(2): 134-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9463625

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People with Williams syndrome process faces holistically. Author(s): Tager-Flusberg H, Plesa-Skwerer D, Faja S, Joseph RM. Source: Cognition. 2003 August; 89(1): 11-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893122

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Periodic limb movement in sleep in children with Williams syndrome. Author(s): Arens R, Wright B, Elliott J, Zhao H, Wang PP, Brown LW, Namey T, Kaplan P. Source: The Journal of Pediatrics. 1998 November; 133(5): 670-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9821427

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Personality characteristics and behaviour problems in individuals of different ages with Williams syndrome. Author(s): Gosch A, Pankau R. Source: Developmental Medicine and Child Neurology. 1997 August; 39(8): 527-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9295848

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Phosphoserine phosphatase deficiency in a patient with Williams syndrome. Author(s): Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E. Source: Journal of Medical Genetics. 1997 July; 34(7): 594-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9222972

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Photoanthropometric study of craniofacial traits in individuals with Williams syndrome. Author(s): Hovis CL, Butler MG. Source: Clinical Genetics. 1997 June; 51(6): 379-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9237500

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Picture of the month--paediatrics. Williams syndrome. Author(s): Shepherd RC, Goel KM. Source: Scott Med J. 1990 April; 35(2): 48. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2374905

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PMS2-related genes flank the rearrangement breakpoints associated with Williams syndrome and other diseases on human chromosome 7. Author(s): Osborne LR, Herbrick JA, Greavette T, Heng HH, Tsui LC, Scherer SW. Source: Genomics. 1997 October 15; 45(2): 402-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9344666

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Portal hypertension in Williams syndrome: report of two patients. Author(s): Casanelles Mdel C, Gil-Fernandez JJ, Casero LF, Bengoechea MG, Serrano R, Ranada JM, Jurado LA. Source: American Journal of Medical Genetics. 2003 May 1; 118A(4): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687671

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Pragmatic language impairment and social deficits in Williams syndrome: a comparison with Down's syndrome and specific language impairment. Author(s): Laws G, Bishop D. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. 2004 January-March; 39(1): 45-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660186

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Precocious puberty in a Williams syndrome patient. Author(s): Douchi T, Maruta K, Kuwahata R, Nagata Y. Source: Obstetrics and Gynecology. 1999 November; 94(5 Pt 2): 860. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546771

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Prevalence estimation of Williams syndrome. Author(s): Stromme P, Bjornstad PG, Ramstad K. Source: Journal of Child Neurology. 2002 April; 17(4): 269-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088082

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Procedural learning deficit in children with Williams syndrome. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Neuropsychologia. 2001; 39(7): 665-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11311297

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Progressive left main coronary artery obstruction leading to myocardial infarction in a child with Williams syndrome. Author(s): Bonnet D, Cormier V, Villain E, Bonhoeffer P, Kachaner J. Source: European Journal of Pediatrics. 1997 October; 156(10): 751-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9365061

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Progressive vascular lesions in Williams syndrome. Author(s): Ino T, Nishimoto K, Iwahara M, Akimoto K, Tokita A, Kaneko K, Yabuta K. Source: The Journal of Pediatrics. 1985 November; 107(5): 826. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4056992

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Pseudohypertension and Williams syndrome. Author(s): Bastianon V. Source: Pediatric Cardiology. 1996 March-April; 17(2): 132. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8833503

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Pseudohypertension in a child with Williams syndrome. Author(s): Narasimhan C, Alexander T, Krishnaswami S. Source: Pediatric Cardiology. 1993 March; 14(2): 124-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8469630

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Pulmonary hypertension associated with portal hypertension in a child with Williams syndrome--a case report. Author(s): Land SD, Shah MD, Berman WF. Source: Pediatr Pathol. 1994 January-February; 14(1): 61-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8159621

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Radioulnar synostosis in Williams syndrome. Author(s): Bzduch V, Spissak L. Source: The Journal of Pediatrics. 1989 July; 115(1): 165. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2738785

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Radio-ulnar synostosis in Williams syndrome. A frequently associated anomaly. Author(s): Charvat KA, Hornstein L, Oestreich AE. Source: Pediatric Radiology. 1991; 21(7): 508-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1771116

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Radioulnar synostosis in Williams syndrome: a historical overview. Author(s): Bzduch V. Source: American Journal of Medical Genetics. 1994 May 1; 50(4): 386. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8209922

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Reading and phonological awareness in Williams syndrome. Author(s): Menghini D, Verucci L, Vicari S. Source: Neuropsychology. 2004 January; 18(1): 29-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744185

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Reading the windows to the soul: evidence of domain-specific sparing in Williams syndrome. Author(s): Tager-Flusberg H, Boshart J, Baron-Cohen S. Source: Journal of Cognitive Neuroscience. 1998 September; 10(5): 631-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9802996

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Reduced stereoacuity in Williams syndrome. Author(s): Sadler LS, Olitsky SE, Reynolds JD. Source: American Journal of Medical Genetics. 1996 December 18; 66(3): 287-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985489

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Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients. Author(s): Wu YQ, Bejjani BA, Tsui LC, Mandel A, Osborne LR, Shaffer LG. Source: American Journal of Medical Genetics. 2002 April 22; 109(2): 121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977160

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Renal abnormalities associated with Williams syndrome. Author(s): Suzuki Y, Shimazaki S, Kaneko K, Ino T, Yabuta K. Source: The Journal of Pediatrics. 1992 October; 121(4): 667. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1403410

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Renal findings in 40 individuals with Williams syndrome. Author(s): Pober BR, Lacro RV, Rice C, Mandell V, Teele RL. Source: American Journal of Medical Genetics. 1993 May 15; 46(3): 271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8488870

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Renal insufficiency in Williams syndrome. Author(s): Biesecker LG, Laxova R, Friedman A. Source: American Journal of Medical Genetics. 1987 September; 28(1): 131-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3314505

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Restenosis and pseudoaneurysm formation after stent placement for aortic coarctation in Williams syndrome. Author(s): Apostolopoulou SC, Kelekis NL, Laskari C, Kaklamanis L, Rammos S. Source: Journal of Vascular and Interventional Radiology : Jvir. 2002 May; 13(5): 547-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11997368

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Review of referrals for the FISH detection of Williams syndrome highlights the importance of testing in supravalvular aortic stenosis/pulmonary stenosis. Author(s): St Heaps L, Robson L, Smith A. Source: American Journal of Medical Genetics. 2001 January 1; 98(1): 109-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11428332

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Rickets in an infant with Williams syndrome. Author(s): Mathias RS. Source: Pediatric Nephrology (Berlin, Germany). 2000 June; 14(6): 489-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10872191

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Rieger's and Williams syndrome. A rare clinical case. Author(s): Balacco-Gabrieli C, Lorusso VV, La Torre M. Source: Ophthalmic Paediatr Genet. 1985 December; 6(3): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4094730

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Second-order belief attribution in Williams syndrome: intact or impaired? Author(s): Sullivan K, Tager-Flusberg H. Source: Am J Ment Retard. 1999 November; 104(6): 523-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10587733

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Sedation for Magnetic Resonance Imaging in a child affected with Williams syndrome. Author(s): Baldinelli F, DeCarli A, Accinelli G. Source: Minerva Anestesiol. 2003 March; 69(3): 169-73, 173-75,. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792585

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Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome. Author(s): Calamandrei G, Alleva E, Cirulli F, Queyras A, Volterra V, Capirci O, Vicari S, Giannotti A, Turrini P, Aloe L. Source: Developmental Medicine and Child Neurology. 2000 November; 42(11): 746-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104346

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Shifting attention and joint attention dissociation in Williams syndrome: implications for the cerebellum and social deficits in autism. Author(s): Lincoln A, Lai Z, Jones W. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2002; 8(3): 226-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119319

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Short-term memory in children with Williams syndrome: a reduced contribution of lexical--semantic knowledge to word span. Author(s): Vicari S, Carlesimo G, Brizzolara D, Pezzini G. Source: Neuropsychologia. 1996 September; 34(9): 919-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8822738

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Single signal of the Williams syndrome chromosome region 1 gene in hyperploidic bone marrow cells of acute lymphoblastic leukemia in a Williams syndrome patient. Author(s): Culic V, Culic S, Armanda V, Resic B, Lasan R, Peterlin B. Source: Medical and Pediatric Oncology. 2002 March; 38(3): 205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836725

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Skin elastic fibers in Williams syndrome. Author(s): Dridi SM, Ghomrasseni S, Bonnet D, Aggoun Y, Vabres P, Bodemer C, Lyonnet S, de Prost Y, Fraitag S, Pellat B, Sidi D, Godeau G. Source: American Journal of Medical Genetics. 1999 November 19; 87(2): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10533027

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Spatial breakdown in spatial construction: evidence from eye fixations in children with Williams syndrome. Author(s): Hoffman JE, Landau B, Pagani B. Source: Cognitive Psychology. 2003 May; 46(3): 260-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694695

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Spatial representation and attention in toddlers with Williams syndrome and Down syndrome. Author(s): Brown JH, Johnson MH, Paterson SJ, Gilmore R, Longhi E, Karmiloff-Smith A. Source: Neuropsychologia. 2003; 41(8): 1037-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667539

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Spontaneous regression of peripheral pulmonary artery stenosis in Williams syndrome. Author(s): Miyamura H, Watanabe H, Tatebe S, Eguchi S. Source: Japanese Circulation Journal. 1996 May; 60(5): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8803725

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Strabismus in Williams syndrome. Author(s): Roy FH. Source: American Journal of Ophthalmology. 1995 August; 120(2): 266-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503903

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Stroke in Williams syndrome. Author(s): Wollack JB, Kaifer M, LaMonte MP, Rothman M. Source: Stroke; a Journal of Cerebral Circulation. 1996 January; 27(1): 143-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8553392

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Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Author(s): Lowery MC, Morris CA, Ewart A, Brothman LJ, Zhu XL, Leonard CO, Carey JC, Keating M, Brothman AR. Source: American Journal of Human Genetics. 1995 July; 57(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7611295

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Subnormal binocular vision in the Williams syndrome. Author(s): Olitsky SE, Sadler LS, Reynolds JD. Source: Journal of Pediatric Ophthalmology and Strabismus. 1997 January-February; 34(1): 58-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9027682

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Sudden death in Williams syndrome: report of ten cases. Author(s): Bird LM, Billman GF, Lacro RV, Spicer RL, Jariwala LK, Hoyme HE, ZamoraSalinas R, Morris C, Viskochil D, Frikke MJ, Jones MC. Source: The Journal of Pediatrics. 1996 December; 129(6): 926-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8969740

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Sudden death of a 21-year-old female with Williams syndrome showing rare complications. Author(s): Imashuku S, Hayashi S, Kuriyama K, Hibi S, Tabata Y, Todo S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2000 June; 42(3): 322-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881597

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Supravalvular aortic stenosis without Williams syndrome. Author(s): Ozergin U, Sunam GS, Yeniterzi M, Yuksek T, Solak T, Solak H. Source: The Thoracic and Cardiovascular Surgeon. 1996 August; 44(4): 219-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8896169

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Supravalvular aortic stenosis, Williams syndrome and sudden death. A case report. Author(s): Suarez-Mier MP, Morentin B. Source: Forensic Science International. 1999 November 22; 106(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10629967

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Syntax and morphology in Williams syndrome. Author(s): Clahsen H, Almazan M. Source: Cognition. 1998 September; 68(3): 167-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9852664

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Systemic hypertension secondary to peripheral vascular anomalies in patients with Williams syndrome. Author(s): Daniels SR, Loggie JM, Schwartz DC, Strife JL, Kaplan S. Source: The Journal of Pediatrics. 1985 February; 106(2): 249-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3968613

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Temperament in Williams syndrome. Author(s): Plissart L, Borghgraef M, Fryns JP. Source: Genet Couns. 1996; 7(1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8652087

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TFII-I, a candidate gene for Williams syndrome cognitive profile: parallels between regional expression in mouse brain and human phenotype. Author(s): Danoff SK, Taylor HE, Blackshaw S, Desiderio S. Source: Neuroscience. 2004; 123(4): 931-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751286

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The BCL7 gene family: deletion of BCL7B in Williams syndrome. Author(s): Jadayel DM, Osborne LR, Coignet LJ, Zani VJ, Tsui LC, Scherer SW, Dyer MJ. Source: Gene. 1998 December 11; 224(1-2): 35-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9931421

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The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Author(s): Kitagawa H, Fujiki R, Yoshimura K, Mezaki Y, Uematsu Y, Matsui D, Ogawa S, Unno K, Okubo M, Tokita A, Nakagawa T, Ito T, Ishimi Y, Nagasawa H, Matsumoto T, Yanagisawa J, Kato S. Source: Cell. 2003 June 27; 113(7): 905-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837248

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The gene for replication factor C subunit 2 (RFC2) is within the 7q11.23 Williams syndrome deletion. Author(s): Peoples R, Perez-Jurado L, Wang YK, Kaplan P, Francke U. Source: American Journal of Human Genetics. 1996 June; 58(6): 1370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8651315

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The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion associated with the Williams syndrome. Author(s): Perez Jurado LA, Li X, Francke U. Source: Cytogenetics and Cell Genetics. 1995; 70(3-4): 246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7789182

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The iris in Williams syndrome. Author(s): Holmstrom G, Almond G, Temple K, Taylor D, Baraitser M. Source: Archives of Disease in Childhood. 1990 September; 65(9): 987-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2221973

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The murine CYLN2 gene: genomic organization, chromosome localization, and comparison to the human gene that is located within the 7q11.23 Williams syndrome critical region. Author(s): Hoogenraad CC, Eussen BH, Langeveld A, van Haperen R, Winterberg S, Wouters CH, Grosveld F, De Zeeuw CI, Galjart N. Source: Genomics. 1998 November 1; 53(3): 348-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9799601

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The neuropathology of Williams syndrome. Report of a 35-year-old man with presenile beta/A4 amyloid plaques and neurofibrillary tangles. Author(s): Golden JA, Nielsen GP, Pober BR, Hyman BT. Source: Archives of Neurology. 1995 February; 52(2): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7848137

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The roles of verbal short-term memory and working memory in the acquisition of grammar by children with Williams syndrome. Author(s): Robinson BF, Mervis CB, Robinson BW. Source: Developmental Neuropsychology. 2003; 23(1-2): 13-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730018

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The Williams syndrome cognitive profile. Author(s): Mervis CB, Robinson BF, Bertrand J, Morris CA, Klein-Tasman BP, Armstrong SC. Source: Brain and Cognition. 2000 December; 44(3): 604-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104544

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The Williams syndrome. Spectrum and significance of ocular features. Author(s): Greenberg F, Lewis RA. Source: Ophthalmology. 1988 December; 95(12): 1608-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3231433

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The Williams syndrome: an Italian collaborative study. Author(s): Franceschini P, Guala A, Vardeu MP, Signorile F, Franceschini D, Mastroiacovo P, Gianotti A, Livini E, Lalatta F, Selicorni A, Andria G, Scarano G, Della Monica M, Rizzo R, Zelante L, Stabile M, Gabrielli O, Neri G. Source: Minerva Pediatr. 1996 October; 48(10): 421-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9017917

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The Williams syndrome: evidence for possible autosomal dominant inheritance. Author(s): Sadler LS, Robinson LK, Verdaasdonk KR, Gingell R. Source: American Journal of Medical Genetics. 1993 September 15; 47(4): 468-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8256806

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The Williams syndrome: objective definition and diagnosis. Author(s): Preus M. Source: Clinical Genetics. 1984 May; 25(5): 422-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6723102

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Three diagnostic signs in Williams syndrome. Author(s): Morris CA, Carey JC. Source: Am J Med Genet Suppl. 1990; 6: 100-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2118769

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Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome. Author(s): Cammareri V, Vignati G, Nocera G, Beck-Peccoz P, Persani L. Source: American Journal of Medical Genetics. 1999 August 27; 85(5): 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405448

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Treating food refusal in a child with Williams syndrome using the parent as therapist in the home setting. Author(s): O'Reilly MF, Lancioni GE. Source: Journal of Intellectual Disability Research : Jidr. 2001 February; 45(Pt 1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168775

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Treatment of children with Williams syndrome with methylphenidate. Author(s): Bawden HN, MacDonald GW, Shea S. Source: Journal of Child Neurology. 1997 June; 12(4): 248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9203066

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Treatment of hyperacusis in Williams syndrome with bilateral conductive hearing loss. Author(s): Miani C, Passon P, Bracale AM, Barotti A, Panzolli N. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2001 September; 258(7): 341-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11699823

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Unbalanced 13;18 translocation and Williams syndrome. Author(s): Colley A, Thakker Y, Ward H, Donnai D. Source: Journal of Medical Genetics. 1992 January; 29(1): 63-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1552549

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Unifocalization of the neck arteries combined with aortic arch replacement for Williams syndrome. Author(s): Yamada Y, Yamagishi M, Shuntoh K, Okano T, Hayashida K, Shinkawa T, Kitamura N. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 March; 123(3): 579-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11882841

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Unusual cognitive and behavioural profile in a Williams syndrome patient with atypical 7q11.23 deletion. Author(s): Gagliardi C, Bonaglia MC, Selicorni A, Borgatti R, Giorda R. Source: Journal of Medical Genetics. 2003 July; 40(7): 526-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843326

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V. Multi-level analysis of cortical neuroanatomy in Williams syndrome. Author(s): Galaburda AM, Bellugi U. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 74-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953235

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Verbal and nonverbal abilities in the Williams syndrome phenotype: evidence for diverging developmental trajectories. Author(s): Jarrold C, Baddeley AD, Hewes AK. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1998 May; 39(4): 511-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9599779

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VI. Genome structure and cognitive map of Williams syndrome. Author(s): Korenberg JR, Chen XN, Hirota H, Lai Z, Bellugi U, Burian D, Roe B, Matsuoka R. Source: Journal of Cognitive Neuroscience. 2000; 12 Suppl 1: 89-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953236

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Visual and spatial working memory dissociation: evidence from Williams syndrome. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Developmental Medicine and Child Neurology. 2003 April; 45(4): 269-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647929

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Visual and visuospatial development in young children with Williams syndrome. Author(s): Atkinson J, Anker S, Braddick O, Nokes L, Mason A, Braddick F. Source: Developmental Medicine and Child Neurology. 2001 May; 43(5): 330-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368486

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Visual information process in Williams syndrome: intact motion detection accompanied by typical visuospatial dysfunctions. Author(s): Nakamura M, Kaneoke Y, Watanabe K, Kakigi R. Source: The European Journal of Neuroscience. 2002 November; 16(9): 1810-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431234

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Visuo-spatial and linguistic abilities in a twin with Williams syndrome. Author(s): Volterra V, Longobardi E, Pezzini G, Vicari S, Antenore C. Source: Journal of Intellectual Disability Research : Jidr. 1999 August; 43 ( Pt 4): 294-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466868

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Visuospatial cognition in Williams syndrome: reviewing and accounting for the strengths and weaknesses in performance. Author(s): Farran EK, Jarrold C. Source: Developmental Neuropsychology. 2003; 23(1-2): 173-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730024

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Vitamin-D-binding protein in the Williams syndrome and idiopathic hypercalcemia. Author(s): Daiger SP, Miller M, Romeo G, Parsons M, Cavalli-Sforza LL. Source: The New England Journal of Medicine. 1978 March 23; 298(12): 687-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=628393

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Vocal cord abnormalities in Williams syndrome: a further manifestation of elastin deficiency. Author(s): Vaux KK, Wojtczak H, Benirschke K, Jones KL. Source: American Journal of Medical Genetics. 2003 June 15; 119A(3): 302-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784297

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Why should neurologists be interested in Williams syndrome? Author(s): Rossen ML, Sarnat HB. Source: Neurology. 1998 July; 51(1): 8-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9674768

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Williams syndrome and deficiency in visuospatial recognition. Author(s): Nakamura M, Watanabe K, Matsumoto A, Yamanaka T, Kumagai T, Miyazaki S, Matsushima M, Mita K. Source: Developmental Medicine and Child Neurology. 2001 September; 43(9): 617-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570631

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Williams syndrome and related disorders. Author(s): Morris CA, Mervis CB. Source: Annual Review of Genomics and Human Genetics. 2000; 1: 461-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701637

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Williams syndrome and the brain. Author(s): Lenhoff HM, Wang PP, Greenberg F, Bellugi U. Source: Scientific American. 1997 December; 277(6): 68-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9388834

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Williams syndrome as a model of genetically determined right-hemisphere dominance. Author(s): Bogdanov NN, Solonichenko VG. Source: Neuroscience and Behavioral Physiology. 1997 May-June; 27(3): 264-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9194063

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Williams syndrome associated with chronic renal failure and various endocrinological abnormalities. Author(s): Ichinose M, Tojo K, Nakamura K, Matsuda H, Tokudome G, Ohta M, Sakai S, Sakai O. Source: Intern Med. 1996 June; 35(6): 482-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835601

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Williams syndrome associated with complete atrioventricular septal defect. Author(s): Nakamoto S, Saga T, Shinohara T. Source: Heart (British Cardiac Society). 2003 May; 89(5): E15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695480

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Williams syndrome cognitive profile also characterizes Velocardiofacial/DiGeorge syndrome. Author(s): Bearden CE, Wang PP, Simon TJ. Source: American Journal of Medical Genetics. 2002 August 8; 114(6): 689-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210289

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Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Author(s): Hirota H, Matsuoka R, Chen XN, Salandanan LS, Lincoln A, Rose FE, Sunahara M, Osawa M, Bellugi U, Korenberg JR. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2003 July-August; 5(4): 311-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865760

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Williams syndrome in Slovakia. Author(s): Bzduch V. Source: American Journal of Medical Genetics. 1996 November 11; 65(4): 366. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8923954

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Williams syndrome starts making sense. Author(s): Ashkenas J. Source: American Journal of Human Genetics. 1996 October; 59(4): 756-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8808588

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Williams syndrome: 15 years of psychological research. Author(s): Mervis CB. Source: Developmental Neuropsychology. 2003; 23(1-2): 1-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730017

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Williams syndrome: a guide to diagnosis and treatment. Author(s): Gustafson R, Traub D. Source: S D J Med. 1997 March; 50(3): 89-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9078861

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Williams syndrome: an update on clinical and molecular aspects. Author(s): Metcalfe K. Source: Archives of Disease in Childhood. 1999 September; 81(3): 198-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10451389

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Williams syndrome: neuronal size and neuronal-packing density in primary visual cortex. Author(s): Galaburda AM, Holinger DP, Bellugi U, Sherman GF. Source: Archives of Neurology. 2002 September; 59(9): 1461-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223034

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Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. Author(s): Tassabehji M, Metcalfe K, Karmiloff-Smith A, Carette MJ, Grant J, Dennis N, Reardon W, Splitt M, Read AP, Donnai D. Source: American Journal of Human Genetics. 1999 January; 64(1): 118-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9915950

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Williams syndrome--does early diagnosis matter? Author(s): Kaplan P. Source: Clinical Pediatrics. 2002 May; 41(4): 277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12041725

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Williams syndrome--the Singapore General Hospital experience. Author(s): Teo SH, Chan DK, Yong MH, Ng IS, Wong KY, Knight L, Ho LY. Source: Ann Acad Med Singapore. 1997 May; 26(3): 360-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9285033

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Word learning in a special population: do individuals with Williams syndrome obey lexical constraints? Author(s): Stevens T, Karmiloff-Smith A. Source: Journal of Child Language. 1997 October; 24(3): 737-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9519593

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CHAPTER 2. NUTRITION AND WILLIAMS SYNDROME Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Williams syndrome.

Finding Nutrition Studies on Williams Syndrome 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 “Williams syndrome” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Williams syndrome” (or a synonym): •

Body composition, energy expenditure, and energy intake in patients with Williams syndrome. Author(s): Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, USA. Source: Kaplan, A S Stallings, V A Zemel, B S Green, K A Kaplan, P J-Pediatr. 1998 February; 132(2): 223-7 0022-3476

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Growth hormone treatment in a child with Williams-Beuren syndrome: a case report. Author(s): Department of Endocrinology, Wilhelmina Children's Hospital, Utrecht University, The Netherlands. [email protected] Source: Kuijpers, G M De Vroede, M Knol, H E Jansen, M Eur-J-Pediatr. 1999 June; 158(6): 451-4 0340-6199

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Intrauterine hypercalcaemia and non-immune hydrops fetalis--relationship to the Williams syndrome. Author(s): King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. Source: Westgren, M Eastham, W N Ghandourah, S Woodhouse, N Prenat-Diagn. 1988 June; 8(5): 333-7 0197-3851

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Rickets in an infant with Williams syndrome. Author(s): Department of Pediatrics, University of California Medical Center, San Francisco 94143-0748, USA. Source: Mathias, R S Pediatr-Nephrol. 2000 June; 14(6): 489-92 0931-041X

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Williams syndrome: an historical perspective of its evolution, natural history, and etiology. Author(s): Department of Pediatrics, University of California, San Diego. Source: Jones, K L Am-J-Med-Genet-Suppl. 1990; 689-96 1040-3787

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND WILLIAMS SYNDROME Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Williams syndrome. 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 Williams syndrome 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 “Williams syndrome” (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 Williams syndrome: •

Adjunct diagnostic test for Angelman syndrome: the tuning fork response. Author(s): Hall BD. Source: American Journal of Medical Genetics. 2002 May 1; 109(3): 238-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977186

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Autism as a neurodevelopmental disorder affecting communication and learning in early childhood: prenatal origins, post-natal course and effective educational support. Author(s): Trevarthen C. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2000 July-August; 63(12): 41-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10970712

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Block design performance in the Williams syndrome phenotype: a problem with mental imagery? Author(s): Farran EK, Jarrold C, Gathercole SE. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2001 September; 42(6): 719-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583244

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Early categorization abilities in young children with Williams syndrome. Author(s): Nazzi T, Karmiloff-Smith A. Source: Neuroreport. 2002 July 19; 13(10): 1259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151782

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Genetics and cardiac anomalies: the heart of the matter. Author(s): Prasad C, Chudley AE. Source: Indian J Pediatr. 2002 April; 69(4): 321-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019554

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Huldre folk of elfame: a case of hidden infirmities. Author(s): Weber KT. Source: Cardiovascular Research. 1997 November; 36(2): 132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9463624

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Treatment of hyperacusis in Williams syndrome with bilateral conductive hearing loss. Author(s): Miani C, Passon P, Bracale AM, Barotti A, Panzolli N. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery.

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/

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 WILLIAMS SYNDROME Overview In this chapter, we will give you a bibliography on recent dissertations relating to Williams syndrome. 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 “Williams syndrome” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Williams syndrome, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Williams Syndrome 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 Williams syndrome. 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: •

A comparative case study of persons with Williams syndrome and musical interests by Milne, Henry James Ogston; PhD from The University of Connecticut, 2001, 268 pages http://wwwlib.umi.com/dissertations/fullcit/3038043

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A DESCRIPTION OF THE PSYCHOLINGUISTIC ABILITIES OF A WILLIAMS SYNDROME POPULATION by NEALE, MARIAN M., EDD from The American University, 1980, 277 pages http://wwwlib.umi.com/dissertations/fullcit/8019135

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A neuropsychological model for the development of the cognitive profiles in mental retardation syndromes: Evidence from Down syndrome and Williams syndrome by Edgin, Jamie Ogline; PhD from University of Denver, 2003, 91 pages http://wwwlib.umi.com/dissertations/fullcit/3086381

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Children with Prader-Willi syndrome vs. Williams syndrome: Parents' attributional cues on a jigsaw puzzle task by Ly, Tran My; PhD from University of California, Los Angeles, 2003, 86 pages http://wwwlib.umi.com/dissertations/fullcit/3089041

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Living in a hello world: An autoethnographic study of the interplay of cognition, genetics and culture in Williams syndrome* by Zitzer-Comfort, Carol Ruth; PhD from The Claremont Graduate University, 2003, 272 pages http://wwwlib.umi.com/dissertations/fullcit/3086766

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The development of visuospatial attentional orienting: Evidence from normally developing children, children with specific language impairment, and adults with Williams syndrome by Schul, Rina; PhD from University of California, San Diego and San Diego State University, 2003, 144 pages http://wwwlib.umi.com/dissertations/fullcit/3083455

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. BOOKS ON WILLIAMS SYNDROME Overview This chapter provides bibliographic book references relating to Williams syndrome. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Williams syndrome 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 “Williams syndrome” (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 Williams syndrome: •

Communication and Language Acquisition: Discoveries from Atypical Development Source: Baltimore, MD: Paul H. Brookes Publishing Company. 1997. 352 p. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775 or (410) 337-9580. Fax (410) 337-8539. E-mail: [email protected]. Website: www.brookespublishing.com. PRICE: $44.00 plus shipping and handling. ISBN: 1557662797. Summary: This text explores research on atypical communication and language development as a source of knowledge about how children become accomplished communicators. The authors describe findings from their own research programs to illustrate how research with children who do not acquire language rapidly and smoothly can help to answer questions essential to the entire field of language and communication development. Twelve chapters cover the classical developmental

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theories and atypical communication development, the contributions of stimulus control perspectives to psycholinguistic theories of vocabulary development and delay, the problems of small sample sizes and scientific conclusions, the developmental relations between cognition and language (Williams syndrome), the skills approach to early language development, the theory of the mind and language acquisition, the linguistic profile of specific language impairment (SLI), the comprehension and language acquisition of youths with severe cognitive disabilities, the communication and language of young children who are deaf and their mothers, the language learning of children reared in poverty, the facilitative effects of input on children's language development, and the theoretical and applied insights from multimedia facilitation of communication skill (in children with autism, deafness, and other disabilities). Each chapter includes extensive references, and a subject index concludes the volume.

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

Journey from Cognition to Brain to Gene: Perspectives from Williams Syndrome by Ursula Bellugi (Editor), Marie I. St. George; ISBN: 0262523124; http://www.amazon.com/exec/obidos/ASIN/0262523124/icongroupinterna

•

The Official Parent's Sourcebook on Williams Syndrome: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597831238; http://www.amazon.com/exec/obidos/ASIN/0597831238/icongroupinterna

•

Understanding Williams Syndrome: Behavioral Patterns and Interventions by Eleanor Semel, Sue R. Rosner; ISBN: 0805826173; http://www.amazon.com/exec/obidos/ASIN/0805826173/icongroupinterna

•

Williams Syndrome by Eleanor Rosner, Sue R. Semel; ISBN: 1557865620; http://www.amazon.com/exec/obidos/ASIN/1557865620/icongroupinterna

•

Williams Syndrome Across Languages (Language Acquisition and Language Disorders, 36) by Susanne Bartke (Editor), Julia Siegmuller (Editor); ISBN: 1588114945; http://www.amazon.com/exec/obidos/ASIN/1588114945/icongroupinterna

•

Williams Syndrome: A Special Double Issue of Developmental Neuropsychology by Mervis (Editor); ISBN: 0805896120; http://www.amazon.com/exec/obidos/ASIN/0805896120/icongroupinterna

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

Williams Syndrome: Hypercalcemia, Supravalvular Aortic Stenosis, Elfin Facies, and Mental Retardation Syndrome Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 171-177. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (212) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Williams syndrome is a multisystem disorder that includes hypercalcemia, supravulvular aortic stenosis, characteristic facial features, distinctive behavioral characteristics, and mental retardation. This chapter on Williams syndrome is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 1 figure. 8 references.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute8: •

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

•

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

•

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

•

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

•

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

•

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

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

•

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

8

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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

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

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

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

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

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

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

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

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

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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

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

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

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

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

•

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

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.9 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:10 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

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

•

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

•

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

•

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

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

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

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

•

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

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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

9

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

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•

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

•

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

The NLM Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Williams syndrome” (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 672 7 104 0 348 1131

HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.15 Simply search by “Williams syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

11

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

12

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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15

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

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

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Coffee Break: Tutorials for Biologists16 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.17 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.18 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

The Genome Project and Williams Syndrome In the following section, we will discuss databases and references which relate to the Genome Project and Williams syndrome. 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).19 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. 16 Adapted 17

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 18 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. 19 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Williams syndrome” (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 Williams syndrome: •

Williams-Beuren Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194050

•

Williams-Beuren Syndrome Chromosome Region 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603431

•

Williams-Beuren Syndrome Chromosome Region 14 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605678

•

Williams-Beuren Syndrome Chromosome Region 5 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605719 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

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

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

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•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Williams syndrome” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database20 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 Database21 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “Williams syndrome” (or synonyms) into the search

20

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 21 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 Williams syndrome can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 Williams syndrome. 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 Williams syndrome. 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 “Williams syndrome”:

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Bile Duct Diseases http://www.nlm.nih.gov/medlineplus/bileductdiseases.html Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Facial Injuries and Disorders http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Head and Brain Malformations http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html Hemophilia http://www.nlm.nih.gov/medlineplus/hemophilia.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Tourette Syndrome http://www.nlm.nih.gov/medlineplus/tourettesyndrome.html Turner's Syndrome http://www.nlm.nih.gov/medlineplus/turnerssyndrome.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Williams syndrome. 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: •

Williams Syndrome Source: Bethesda, MD: National Institute of Neurological Disorders and Stroke. 1997. [1 p.]. Contact: Available from National Institute of Neurological Disorders and Stroke. Office of Scientific and Health Reports, P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424 or (301) 496-5751. PRICE: Single copy free. Summary: This fact sheet from the National Institute of Neurological Disorders and Stroke describes Williams syndrome, a rare, congenital (present at birth) disorder

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characterized by physical and developmental problems. Common features include elfin facial features, heart and blood vessel problems, hypercalcemia, low birth weight, slow weight gain, feeding problems, irritability during infancy, dental and kidney abnormalities, hyperacusis (sensitive hearing), musculoskeletal problems, an impulsive and outgoing personality, limited spatial skills and motor control, and intellectual disability (i.e., developmental delay, learning disabilities, mental retardation, or attention deficit disorder). The fact sheet describes the syndrome, treatment options, prognosis, and present research efforts on the disorder. The fact sheet concludes with the telephone numbers and addresses for four organizations through which readers can obtain more information. 6 references. 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: •

Frequently Asked Questions About Williams Syndrome Summary: These are frequently asked questions about Williams syndrome. Source: Williams Syndrome Association, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7672 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 Williams syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm.

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

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Williams Syndrome The following is a list of associations that provide information on and resources relating to Williams syndrome: •

Canadian Association for Williams Syndrome Telephone: (604) 853-0231 Fax: (604) 853-0232 Email: [email protected] Web Site: http://www.bmts.com/~williams/caws.htm Background: The Canadian Association for Williams Syndrome (CAWS) is a voluntary nonprofit organization dedicated to providing support and assistance to families with children affected by Williams Syndrome; maintaining a network for adults with Williams Syndrome; and supporting research into educational, behavioral, social, and medical aspects of this syndrome. Williams Syndrome is a rare congenital disorder characterized by heart and blood vessel abnormalities, high blood calcium levels, developmental delays, characteristic facial features, and/or additional abnormalities. Established in 1984 as a parent support group, the Association currently consists of 10 chapters and 360 members. CAWS is committed to locating affected families who are unaware of the Association; becoming a visible group in the medical, scientific, educational, and professional communities in order to facilitate referrals of newly diagnosed individuals; and providing a variety of educational materials to affected individuals, family members, and health care professionals. Relevant area(s) of interest: Beuren Syndrome, Williams Syndrome

•

Williams Syndrome Association Telephone: (248) 244-2229 Fax: (248) 244-2230 Email: [email protected] or [email protected] Web Site: http://www.williams-syndrome.org

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Background: The Williams Syndrome Association is a national voluntary not-for-profit organization dedicated to improving the lives of individuals with Williams Syndrome, a rare congenital disorder characterized by heart and blood vessel abnormalities, high blood calcium levels, developmental delays, characteristic facial features, and/or additional abnormalities. Established in 1983, the Association is committed to locating affected individuals and their families, and disseminating current medical and educational information to families, professionals, and the public. In addition, the organization seeks to increase professional awareness of, and interest in, Williams Syndrome and supports ongoing research into the educational, behavioral, social, and medical aspects of the disorder. The Williams Syndrome Association engages in patient and family advocacy; provides appropriate referrals including to support groups; and holds annual regional conferences, social gatherings, and biennial conventions. The Association also provides a variety of informational materials to families, health care professionals, teachers, and others through its database, directory, quarterly newsletter, reports, medical monitoring guidelines for physicians, brochures, pamphlets, and audiovisual aids. Relevant area(s) of interest: Beuren Syndrome, Williams Syndrome

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Williams syndrome. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Williams syndrome. 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 Williams syndrome. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Williams syndrome” (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

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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 “Williams syndrome”. 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 “Williams syndrome” (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 “Williams syndrome” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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

•

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

•

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

•

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

•

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

•

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

23

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

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•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

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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

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Williams syndrome: •

Basic Guidelines for Williams Syndrome ADD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001551.htm Williams syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001116.htm

•

Signs & Symptoms for Williams Syndrome Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Epicanthal folds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003030.htm

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Flattened nasal bridge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003056.htm Hypercalcemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000365.htm Microcephaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003272.htm Pectus excavatum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003320.htm Short stature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003271.htm •

Diagnostics and Tests for Williams Syndrome ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Hypercalcemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003486.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm

•

Background Topics for Williams Syndrome Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm

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

Online Glossaries 117

•

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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WILLIAMS SYNDROME DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Actin: Essential component of the cell skeleton. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] 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] 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] Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps

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to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino 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] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH]

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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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [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] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [NIH] Aortic Stenosis, Supravalvular: A narrowing of the aorta in the region above the aortic valve. [NIH] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [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)

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is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Perception: The process whereby auditory stimuli are selected, organized and interpreted by the organism; includes speech discrimination. [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] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH]

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Binocular vision: The blending of the separate images seen by each eye into a single image; allows images to be seen with depth. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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

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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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH]

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Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] 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 Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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 Deletion: Actual loss of a portion of the chromosome. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic

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engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices 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

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theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

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] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [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] 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 Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to

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which a subject has learned to respond. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [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] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH]

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Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular

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dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [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] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] 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] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are

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sometimes considered part of the epithalamus. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [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] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Nerve Diseases: Diseases of the facial nerve or nuclei. Pontine disorders may affect the facial nuclei or nerve fascicle. The nerve may be involved intracranially, along its course through the petrous portion of the temporal bone, or along its extracranial course. Clinical manifestations include facial muscle weakness, loss of taste from the anterior tongue, hyperacusis, and decreased lacrimation. [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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH]

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Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] 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] 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] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration

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following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [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] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH]

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Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hyperacusis: An abnormally disproportionate increase in the sensation of loudness in response to auditory stimuli of normal volume. Cochlear diseases; vestibulocochlear nerve diseases; facial nerve diseases; stapes surgery; and other disorders may be associated with this condition. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] 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] 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 response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU]

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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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It

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consists of three distinct parts: an anterior limb, posterior limb, and genu. [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] Intravascular: Within a vessel or vessels. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH]

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Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lipid: Fat. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] 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] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU]

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Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] 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]

Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms

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include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle

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known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [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]

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Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]

Octamer: Eight molecules of histone. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and

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secrete some of the female sex hormones. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] 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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phobias: An exaggerated and invariably pathological dread of some specific type of stimulus or situation. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH]

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Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] 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]

Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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]

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Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU]

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Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoacoustics: The science pertaining to the interrelationship of psychologic phenomena and the individual's response to the physical properties of sound. [NIH] Psycholinguistics: A discipline concerned with relations between messages and the characteristics of individuals who select and interpret them; it deals directly with the processes of encoding (phonetics) and decoding (psychoacoustics) as they relate states of messages to states of communicators. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [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] 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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral

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mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Research Support: Financial support of research activities. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] 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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]

Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated

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insulin pumps and other prostheses. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] 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] Semantics: The relationships between symbols and their meanings. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological

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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]

Sociability: The tendency of organisms to grow together with others of the same kind. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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] 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 pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH]

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Speech Perception: The process whereby an utterance is decoded into a representation in terms of linguistic units (sequences of phonetic segments which combine to form lexical and grammatical morphemes). [NIH] Sperm: The fecundating fluid of the male. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striate: Recurrent branch of the anterior cerebral artery which supplies the anterior limb of the internal capsule. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the

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hematopoietic system and elsewhere. [NIH] 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]

Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] 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] Synostosis: The joining of contiguous and separate bones by osseous tissue. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH]

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Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Thermal: Pertaining to or characterized by heat. [EU] 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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] 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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] 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] 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

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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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] 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] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] 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] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

Dictionary 153

Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [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] Vocal cord: The vocal folds of the larynx. [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]

Williams Syndrome: A contiguous gene syndrome associated with a heterozygous microdeletion in the chromosomal region 7q11.23, encompassing the elastin gene. Clinical manifestations include supravalvular aortic stenosis (aortic stenosis, supravalvular), mental

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retardation, elfin facies, impaired visuospatial constructive abilities, and transient hypercalcemia in infancy. The condition affects both sexes, with onset at birth or in early infancy. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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]

155

INDEX 3 3-dimensional, 27, 119 A Abdomen, 119, 142, 149 Aberrant, 8, 22, 31, 32, 119 Abscess, 119, 147 ACE, 20, 49, 119 Actin, 21, 22, 119, 140 Acute lymphoblastic leukemia, 67, 119 Acute lymphocytic leukemia, 119 Adaptation, 14, 119, 143 Adenovirus, 119, 146 Adjustment, 119 Adolescence, 8, 10, 21, 25, 119 Adrenergic, 119, 129, 130, 150 Agammaglobulinemia, 20, 119 Agonist, 119, 129 Algorithms, 7, 119, 123 Alkaline, 120, 123 Alternative medicine, 81, 83, 120 Amino Acids, 120, 142, 144, 146, 152 Amygdala, 28, 30, 32, 33, 120, 122, 137, 147, 150 Amyloid, 70, 120 Anaesthesia, 37, 58, 120, 135 Anal, 38, 120, 137 Analogous, 25, 120, 152 Anatomical, 8, 120, 122, 125, 134, 147 Anemia, 99, 120, 134 Anesthesia, 43, 120, 130 Angiography, 37, 120 Angioplasty, 38, 49, 120 Animal model, 31, 120 Anomalies, 7, 18, 44, 69, 82, 120 Anterior Cerebral Artery, 120, 125, 149 Anterior chamber, 120, 136 Antibacterial, 121, 148 Antibiotic, 121, 148 Antibodies, 121, 134 Anticholinergic, 4, 121 Antigen, 121, 126, 134, 135, 146 Anus, 120, 121, 126, 136 Aorta, 42, 52, 121, 153 Aortic Coarctation, 66, 121 Aortic Stenosis, Supravalvular, 121, 153 Aphasia, 26, 121 Aqueous, 121, 122, 128 Arterial, 45, 48, 121, 125, 134, 144, 150

Arteries, 72, 121, 123, 127, 138, 139 Arterioles, 121, 123 Arteriosus, 121, 145 Artificial Organs, 121, 146 Astrocytes, 121, 122 Astrocytoma, 61, 122 Asymptomatic, 41, 122 Ataxia, 99, 122, 125, 150 Atrioventricular, 43, 75, 122 Atrium, 122, 153 Atrophy, 98, 99, 122 Atypical, 5, 10, 29, 44, 57, 72, 87, 122 Audiovisual Aids, 107, 122 Auditory, 6, 10, 32, 61, 122, 133, 134 Auditory Perception, 61, 122 Axons, 122, 133 B Bacteria, 121, 122, 130, 138, 139, 148, 152 Bacterial Physiology, 119, 122 Bacteriophage, 122, 143, 152 Basal Ganglia, 122, 137 Basal Ganglia Diseases, 122 Base, 122, 128, 136, 141, 143, 150 Beta-pleated, 120, 122 Bilateral, 16, 39, 72, 82, 122 Binocular vision, 68, 123 Biochemical, 15, 20, 123 Biological Factors, 15, 123 Biological therapy, 123, 133 Biological Transport, 123, 128 Biotechnology, 33, 34, 95, 97, 98, 99, 100, 123 Bladder, 3, 123, 132, 144, 152 Blood Coagulation, 123, 124 Blood pressure, 17, 48, 49, 116, 123, 124, 134, 139 Blood vessel, 105, 106, 107, 119, 120, 123, 124, 125, 136, 148, 149, 150, 151, 152 Body Fluids, 123, 129 Bone Marrow, 67, 119, 123, 138, 149 Bone Marrow Cells, 67, 123, 138 Brain Stem, 123, 125, 140 Branch, 113, 123, 128, 130, 141, 142, 148, 149, 150 Breakdown, 67, 123, 132 Bypass, 43, 123 C Calcium, 106, 107, 123, 126, 134, 148

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Carbohydrate, 124, 147 Carcinogenic, 124, 135 Carcinogens, 124, 141 Carcinoma, 124 Cardiac, 17, 44, 58, 75, 82, 124, 130, 140, 150 Cardiovascular, 17, 40, 42, 43, 45, 51, 62, 68, 72, 82, 116, 124 Cardiovascular disease, 17, 45, 51, 124 Case report, 62, 64, 69, 78, 124 Catecholamine, 124, 129 Catheterization, 120, 124 Caudal, 124, 128, 134, 143 Causal, 15, 124 Cell Cycle, 5, 27, 124, 133 Cell Differentiation, 124, 148 Cell Division, 98, 122, 124, 128, 133, 136, 138, 143, 144, 147 Cell motility, 21, 124 Cell proliferation, 124, 146, 148 Cell Size, 30, 124 Cell Survival, 125, 133 Central Nervous System, 8, 125, 128, 132, 138, 141 Cerebellar, 40, 48, 122, 125, 146, 152 Cerebellar Diseases, 122, 125, 152 Cerebellum, 30, 31, 32, 39, 67, 125, 127, 146 Cerebral, 12, 17, 32 Cerebral hemispheres, 12, 122, 123, 125 Cerebral Infarction, 40, 125 Cerebrovascular, 40, 122, 124, 125, 150 Cerebrum, 125, 127, 152 Cervix, 125, 131 Chin, 125, 138 Chromatin, 5, 12, 26, 33, 35, 69, 125, 141 Chromosomal, 7, 13, 52, 59, 76, 125, 153 Chromosome, 8, 12, 13, 15, 19, 33, 42, 44, 50, 51, 55, 59, 63, 67, 70, 75, 98, 125, 133, 147 Chromosome Deletion, 13, 125 Chronic, 74, 98, 125, 130, 135, 136, 143 Chronic renal, 74, 125, 143 Clinical trial, 4, 95, 125, 144 Cloning, 123, 125 Cofactor, 126, 144 Cognition, 5, 10, 11, 12, 16, 17, 25, 28, 29, 31, 32, 86, 88 Collapse, 123, 126 Colon, 98, 126 Communication Disorders, 24, 25, 56, 63, 94, 126 Complement, 126

Complementary and alternative medicine, 81, 83, 126 Complementary medicine, 81, 126 Computational Biology, 95, 97, 126 Concomitant, 32, 43, 127 Conduction, 6, 127 Cone, 22, 127 Connective Tissue, 123, 127, 131, 132, 149 Consciousness, 127, 128, 129 Consultation, 15, 127 Continuum, 13, 127 Contraindications, ii, 127 Conus, 127, 145 Coordination, 125, 127 Coronary, 43, 49, 64, 124, 127, 138, 139 Coronary heart disease, 124, 127 Coronary Thrombosis, 127, 138, 139 Corpus, 43, 60, 127 Corpus Callosum, 60, 127 Cortex, 18, 28, 35, 41, 46, 58, 59, 122, 127, 131, 134, 135, 140, 146 Cortical, 8, 18, 28, 30, 72, 127, 147, 150 Cortices, 30, 127, 133 Cranial, 125, 127, 131, 153 Crossing-over, 127, 145 Cues, 22, 86, 127 Cytogenetics, 7, 46, 52, 70, 128 Cytoplasm, 22, 128, 133, 140, 146 Cytoskeleton, 21, 128, 139 Cytotoxic, 128, 148 D Data Collection, 10, 128 Databases, Bibliographic, 95, 128 Deletion, 8, 12, 13, 15, 17, 20, 27, 31, 34, 36, 42, 44, 52, 55, 59, 69, 70, 72, 128, 132 Dementia, 128, 140 Dendrites, 128, 133, 140 Density, 30, 33, 76, 128, 141, 148 Depolarization, 128, 148 Dermal, 47, 128 Dextroamphetamine, 128, 138 Diabetes Mellitus, 17, 128, 133 Diagnostic procedure, 128 Diastolic, 128, 134 Diencephalon, 128, 130, 134, 140, 151 Diffusion, 18, 28, 123, 128 Digestive tract, 129, 148, 149 Dilatation, 120, 129 Dilation, 38, 129 Diploid, 5, 129, 143 Direct, iii, 129, 146 Discrimination, 122, 129

157

Dissection, 41, 129 Dissociation, 16, 18, 28, 49, 67, 73, 129 Dissociative Disorders, 129 Distal, 13, 129, 144 Diverticula, 3, 129 Diverticulum, 129 Dominance, 74, 129, 136 Dopamine, 19, 128, 129, 142 Dorsal, 12, 18, 30, 31, 32, 46, 49, 61, 129, 130, 143, 147 Dorsum, 129 Duct, 104, 124, 129, 147, 149 Dyes, 120, 129 Dysplasia, 99, 129 Dystrophy, 7, 98, 129 E Ectopic, 20, 130 Elastin, 12, 30, 35, 45, 47, 48, 52, 68, 74, 130, 153 Electroencephalography, 28, 130 Electrophysiological, 30, 31, 32, 54, 130 Embolus, 130, 135 Embryo, 124, 130, 135 Empirical, 5, 6, 24, 29, 130 Endarterectomy, 120, 130 End-stage renal, 125, 130, 143 Energy Intake, 39, 78, 130 Enhancer, 15, 130 Environmental Exposure, 130, 141 Environmental Health, 7, 94, 96, 130 Enzymatic, 124, 126, 130, 146 Enzyme, 119, 130, 138, 148, 153 Epidemiological, 20, 130 Epidermoid carcinoma, 130, 149 Epinephrine, 119, 129, 130, 141, 152 Epithalamus, 128, 130, 137 Epithelium, 131, 136 Erythrocytes, 120, 123, 131 Essential Tremor, 99, 131 Eukaryotic Cells, 131, 135, 141, 152 Evoke, 131, 149 Extracellular, 120, 121, 127, 131 Extrapyramidal, 129, 131 F Facial, 8, 9, 15, 28, 33, 49, 50, 89, 104, 105, 106, 107, 131, 134 Facial Expression, 28, 33, 131 Facial Nerve, 131, 134 Facial Nerve Diseases, 131, 134 Family Planning, 95, 131 Fat, 123, 127, 130, 131, 137, 148 Fetus, 131, 144, 152

Fibrosis, 99, 131, 147 Fissure, 127, 131 Flexion, 19, 131 Fluorescence, 7, 131 Forearm, 123, 131 Fossa, 125, 131 Fractionation, 8, 131 Frontal Lobe, 120, 125, 131 Functional magnetic resonance imaging, 18, 25, 26, 28, 29, 132 Fundus, 131, 132 G Ganglia, 122, 132, 140 Gas, 128, 132, 153 Gastrin, 132, 134 Gastrointestinal, 130, 132, 149, 150 Gastrointestinal tract, 132, 149 Gene, 5, 7, 12, 13, 15, 19, 20, 22, 26, 27, 30, 32, 88, 99, 100 Gene Deletion, 27, 35, 47, 132 Gene Duplication, 7, 132 Gene Expression, 5, 12, 26, 30, 36, 99, 132 Genetic Screening, 7, 132 Genetics, 7, 12, 13, 15, 19, 21, 29, 81, 82, 86, 89 Genital, 132, 152 Genitourinary, 3, 132, 152 Genomics, 12, 34, 35, 36, 49, 51, 53, 63, 70, 74, 132 Genotype, 19, 30, 51, 132, 142 Germ Cells, 132, 138, 141 Gland, 132, 142, 144, 147, 149, 151 Glucose, 98, 128, 132, 133, 135 Glucose Intolerance, 128, 132 Governing Board, 133, 144 Granulocytes, 133, 148, 153 Growth, 3, 6, 22, 44, 52, 58, 59, 78, 98, 119, 121, 124, 125, 133, 138, 140, 141, 143, 151 Growth Cones, 22, 133 Growth factors, 22, 133 Gyrus Cinguli, 120, 133, 137 H Haploid, 5, 133, 143 Hearing Disorders, 126, 133 Heart attack, 124, 133 Heartbeat, 133, 150 Helix-loop-helix, 15, 133 Hemoglobin, 120, 131, 133 Hemoglobinuria, 98, 133 Hemophilia, 99, 104, 133 Hemorrhage, 133, 149 Hereditary, 7, 133, 146

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Heredity, 132, 133 Heritability, 17, 133 Heterozygotes, 129, 133 Hippocampus, 134, 137, 140, 147 Histology, 134, 140 Homogeneous, 127, 134 Homologous, 127, 133, 134, 147, 150 Homozygotes, 129, 134 Hormonal, 122, 134 Hormone, 78, 130, 132, 134, 135, 148, 151 Human Development, 5, 18, 19, 29, 94, 134 Hydrops Fetalis, 56, 78, 134 Hyperacusis, 53, 72, 82, 105, 131, 134 Hypercalcemia, 4, 20, 73, 89, 105, 116, 134, 154 Hypertension, 17, 48, 63, 64, 69, 124, 134, 151 Hypothalamus, 128, 134, 137, 147 I Id, 79, 82, 98, 106, 112, 114, 134 Idiopathic, 4, 73, 134 Immune response, 20, 121, 134, 150, 153 Immune system, 27, 123, 134, 152, 153 Immunodeficiency, 98, 134 Immunoglobulins, 26, 134 Immunologic, 119, 134 Impairment, 10, 16, 25, 31, 63, 86, 88, 122, 134, 138 In situ, 59, 134 In Situ Hybridization, 59, 135 In vitro, 20, 21, 27, 135 In vivo, 20, 22, 27, 135 Indicative, 88, 135, 142, 152 Induction, 8, 10, 22, 135 Infancy, 9, 20, 105, 135, 154 Infantile, 55, 135 Infarction, 125, 135 Infection, 123, 134, 135, 150, 153 Infertility, 13, 135 Inflammation, 131, 135, 141 Initiation, 22, 135, 151 Inotropic, 129, 135 Insight, 6, 28, 135 Insulin, 17, 135, 147 Insulin-dependent diabetes mellitus, 135 Intermediate Filaments, 135, 140 Internal Capsule, 120, 135, 149 Interphase, 7, 136 Intestinal, 136, 137 Intestines, 129, 132, 136, 147 Intracellular, 135, 136, 147 Intravascular, 50, 136

Invasive, 136, 137 Involuntary, 122, 131, 136, 139, 146, 148 Ions, 122, 129, 136, 139 Iris, 70, 120, 121, 136, 145 Ischemia, 122, 136 J Joint, 67, 136, 150 K Kb, 53, 94, 136 Kidney Disease, 94, 99, 136 L Language Development, 10, 87, 136 Language Disorders, 88, 126, 136 Larynx, 136, 153 Latency, 33, 136 Latent, 136, 144 Laterality, 16, 136 Lesion, 25, 31, 137 Leukemia, 6, 27, 98, 137 Leukocytes, 123, 133, 137 Library Services, 112, 137 Ligament, 137, 144 Limbic, 30, 120, 133, 137 Limbic System, 30, 120, 133, 137 Lipid, 135, 137 Lobe, 125, 137 Localization, 5, 8, 16, 20, 49, 70, 137 Localized, 8, 22, 119, 135, 137, 143 Longitudinal Studies, 16, 137 Longitudinal study, 11, 20, 35, 137 Loop, 15, 33, 137 Lumen, 121, 137 Lymphoblastic, 137 Lymphoblasts, 119, 137 Lymphoid, 121, 137 Lymphoma, 62, 98, 137 M Magnetic Resonance Imaging, 18, 25, 26, 28, 30, 66, 137 Malabsorption, 98, 137 Malformation, 41, 138 Malignant, 98, 138 Malnutrition, 122, 138, 139 Manifest, 19, 138 Mediate, 12, 33, 129, 138 MEDLINE, 95, 97, 99, 138 Medullary, 54, 138 Megakaryocytes, 123, 138 Meiosis, 5, 138, 150 Melanin, 136, 138, 142, 152 Melanocytes, 138 Melanoma, 98, 138

159

Membrane, 22, 121, 126, 128, 131, 136, 138, 141, 146, 148 Memory, 6, 10, 16, 25, 26, 27, 37, 51, 54, 59, 67, 70, 73, 128, 138 Meninges, 125, 138 Mental, iv, 4, 5, 6, 8, 11, 14, 16, 20, 24, 26, 27, 29, 82, 85, 89, 94, 96, 100, 105 Mental Health, iv, 4, 20, 26, 94, 96, 138 Mental Processes, 129, 138, 145 Mental Retardation, 4, 5, 6, 8, 11, 14, 20, 24, 27, 29, 85, 89, 100, 105, 126, 138, 154 Metabolic disorder, 8, 138 Methylphenidate, 40, 72, 138 MI, 117, 138 Microbiology, 119, 122, 138 Microorganism, 126, 138, 153 Microtubule-Associated Proteins, 139, 140 Microtubules, 135, 139, 140 Migration, 22, 139 Modeling, 7, 8, 26, 139 Molecular, 7, 12, 13, 14, 15, 19, 22, 27, 29, 31, 95, 97 Molecular Structure, 31, 139 Molecule, 121, 122, 126, 129, 139, 143, 145, 148, 152 Monitor, 139, 141 Morphogenesis, 31, 139 Morphological, 8, 60, 130, 138, 139 Morphology, 17, 43, 55, 60, 69, 139 Motility, 21, 139 Muscle Fibers, 139 Muscular Atrophy, 98, 139 Muscular Dystrophies, 130, 139 Mutagenesis, 20, 139 Mutagens, 139 Mydriatic, 129, 139 Myocardial infarction, 60, 64, 127, 138, 139 Myocardium, 138, 139 Myotonic Dystrophy, 98, 140 N Narcolepsy, 128, 138, 140 Necrosis, 125, 135, 138, 139, 140 Need, 3, 87, 89, 108, 125, 140 Neocortex, 140 Neonatal, 42, 61, 140 Neoplasia, 98, 140 Neoplastic, 137, 140 Nephropathy, 136, 140 Nerve, 22, 119, 120, 122, 125, 128, 131, 133, 140, 144, 146, 147, 149, 152, 153 Nervous System, 8, 99, 125, 140, 141, 150 Networks, 42, 140

Neural, 11, 16, 18, 24, 25, 26, 28, 30, 31, 32, 61, 120, 140, 147 Neural Pathways, 31, 32, 140 Neuroanatomy, 31, 32, 56, 72, 137, 140 Neurofibrillary Tangles, 70, 140 Neurofilaments, 140 Neurologic, 10, 16, 61, 140 Neuronal, 7, 22, 30, 76, 133, 140 Neurons, 8, 22, 30, 128, 132, 140, 150, 153 Neuropsychological Tests, 17, 141 Neuropsychology, 14, 37, 38, 40, 45, 46, 47, 49, 54, 60, 61, 65, 67, 70, 73, 75, 88, 141 Nonverbal Communication, 126, 141 Norepinephrine, 119, 129, 141 Nuclear, 5, 69, 122, 131, 135, 137, 140, 141, 146, 151 Nuclei, 22, 30, 120, 130, 131, 137, 141, 147, 153 Nucleic acid, 135, 139, 141 Nucleosomes, 27, 141 Nucleus, 30, 120, 122, 125, 128, 131, 135, 138, 141, 144, 147, 150, 153 O Occipital Lobe, 141, 153 Occupational Therapy, 89, 141 Octamer, 27, 141 Ocular, 71, 141 Oncogene, 98, 141 On-line, 10, 25, 46, 58, 115, 141 Opacity, 128, 141 Organelles, 128, 138, 141 Otitis, 53, 141 Otitis Media, 53, 141 Ovary, 60, 141, 149 P Pancreas, 135, 142 Pancreatic, 98, 142 Pancreatic cancer, 98, 142 Papilloma, 142, 146 Paralysis, 21, 39, 142 Parenteral, 130, 142 Parietal, 18, 120, 142 Parietal Lobe, 18, 120, 142 Paroxysmal, 98, 142 Particle, 142, 148, 152 Patch, 49, 127, 142 Pathogenesis, 15, 142 Pathologic, 127, 142 Pathophysiology, 19, 28, 142 Patient Education, 104, 110, 112, 117, 142 Pelvic, 142, 144

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Peptide, 142, 144, 151 Perception, 24, 25, 28, 32, 48, 55, 127, 133, 142 Pharmacologic, 120, 142, 151 Phenotype, 5, 7, 12, 13, 15, 30, 32, 35, 39, 47, 51, 53, 69, 72, 82, 132, 142 Phenylalanine, 142, 152 Phobias, 38, 142 Phospholipases, 142, 148 Phosphorus, 124, 143 Phosphorylated, 20, 22, 143 Phosphorylation, 20, 22, 143 Photoreceptors, 143, 147 Physical Therapy, 89, 143 Physiologic, 119, 143, 145, 152 Physiology, 74, 130, 143 Pigment, 138, 143 Plants, 132, 139, 141, 143 Plaque, 120, 143 Plasticity, 8, 18, 25, 143 Platelet Activation, 143, 148 Platinum, 137, 143 Point Mutation, 13, 20, 21, 143 Polycystic, 99, 143 Polymorphic, 35, 143 Posterior, 30, 32, 120, 121, 122, 125, 129, 130, 136, 141, 142, 143 Postnatal, 3, 143 Postsynaptic, 144, 148 Potentiation, 144, 148 Practice Guidelines, 96, 144 Precursor, 129, 130, 141, 142, 144, 152 Predisposition, 32, 144 Prenatal, 18, 56, 81, 116, 130, 132, 144 Presumptive, 15, 144 Prevalence, 3, 19, 54, 63, 144 Progression, 21, 120, 144 Progressive, 64, 124, 125, 128, 133, 139, 140, 143, 144 Projection, 30, 141, 144, 146 Prophase, 144, 150 Prospective study, 137, 144 Prostate, 98, 144 Protein S, 99, 123, 144, 146 Proteins, 5, 12, 21, 22, 27, 120, 121, 125, 126, 133, 135, 139, 140, 142, 144, 151 Protocol, 9, 19, 25, 144 Proximal, 129, 144, 147 Psychiatric, 48, 126, 144 Psychic, 138, 145, 147 Psychoacoustics, 145 Psycholinguistics, 26, 145

Psychology, 23, 26, 27, 39, 41, 50, 56, 57, 67, 72, 82, 129, 141, 145 Psychomotor, 3, 145 Psychophysiology, 141, 145 Puberty, 40, 47, 52, 58, 63, 145 Public Policy, 95, 145 Publishing, 33, 87, 145 Pulmonary, 38, 61, 64, 66, 67, 123, 145, 153 Pulmonary Artery, 67, 123, 145, 153 Pupil, 129, 139, 145 R Race, 139, 145 Radiation, 119, 130, 131, 145, 154 Radiation therapy, 119, 131, 145 Radioactive, 141, 145 Reaction Time, 18, 145 Receptor, 20, 36, 69, 70, 119, 121, 127, 129, 145, 148 Recombination, 5, 12, 145 Rectum, 121, 126, 129, 132, 144, 145 Red Nucleus, 122, 145 Reentry, 43, 146 Refer, 1, 126, 137, 141, 146 Reflex, 48, 146 Refraction, 146, 148 Regurgitation, 59, 146 Reliability, 10, 146 Research Support, 19, 146 Restless legs, 19, 146 Restoration, 143, 146 Retina, 127, 146, 147 Retinal, 127, 146 Retinoblastoma, 27, 98, 146 Retinoblastoma Protein, 27, 146 Ribosome, 146, 152 Risk factor, 17, 144, 146 Robotics, 24, 146 Rods, 22, 146, 147 S Salivary, 131, 142, 147 Sclerosis, 99, 147 Screening, 7, 9, 125, 132, 147 Secretion, 54, 135, 147 Segmentation, 8, 147 Segregation, 145, 147 Seizures, 142, 147 Semantics, 46, 147 Semen, 144, 147 Septal, 75, 120, 137, 147 Septal Nuclei, 120, 137, 147 Sequence Analysis, 42, 147 Serous, 134, 147

161

Sex Characteristics, 119, 145, 147 Sex Determination, 99, 147 Shock, 52, 147 Side effect, 123, 147, 151 Signal Transduction, 12, 20, 22, 147 Skeletal, 13, 36, 139, 148 Skeleton, 119, 136, 148 Skull, 148, 150 Small intestine, 134, 136, 148 Smooth muscle, 148, 150 Sociability, 23, 148 Social Behavior, 23, 148 Soft tissue, 123, 148 Somatic, 119, 137, 138, 148 Somatic cells, 138, 148 Sound wave, 127, 148 Spasm, 58, 148 Specialist, 78, 107, 129, 148 Species, 6, 130, 138, 139, 145, 148, 150, 152, 154 Spectrum, 21, 23, 25, 28, 71, 148 Speech pathologist, 89, 148 Speech Perception, 38, 149 Sperm, 125, 149 Spinal cord, 121, 122, 123, 125, 138, 140, 146, 149 Sporadic, 146, 149 Squamous, 6, 130, 149 Squamous cell carcinoma, 6, 130, 149 Squamous cells, 149 Stapes, 134, 149 Stenosis, 4, 12, 20, 37, 38, 43, 44, 51, 59, 61, 66, 67, 68, 69, 89, 149, 153 Stent, 66, 149 Sterility, 135, 149 Stimulant, 128, 138, 149 Stimulus, 88, 136, 142, 145, 146, 149, 151 Stomach, 129, 132, 134, 136, 148, 149 Stool, 126, 149 Stress, 124, 144, 149 Striate, 18, 149 Stricture, 149 Stroke, 18, 56, 60, 68, 94, 104, 124, 149 Stroma, 136, 149 Stromal, 123, 149 Stromal Cells, 123, 149 Subclinical, 47, 135, 147, 150 Subspecies, 148, 150 Substance P, 147, 150 Sudden death, 60, 68, 69, 150 Support group, 106, 107, 150 Sympathomimetic, 128, 129, 130, 141, 150

Symphysis, 125, 144, 150 Symptomatology, 14, 150 Synapsis, 150 Synaptic, 8, 148, 150 Synostosis, 64, 65, 150 Systemic, 69, 121, 123, 130, 135, 140, 145, 150 Systolic, 134, 150 T Telangiectasia, 99, 150 Temporal, 12, 28, 31, 32, 120, 131, 133, 134, 150 Temporal Lobe, 120, 150 Thalamic, 122, 130, 150 Thalamic Diseases, 122, 150 Thalamus, 128, 130, 137, 150, 151 Thermal, 129, 151 Threshold, 134, 151 Thrombosis, 144, 149, 151 Thrombus, 127, 135, 151 Thyroid, 71, 151, 152 Thyroid Gland, 151 Thyroid Hormones, 151, 152 Thyrotropin, 71, 151 Thyroxine, 142, 151 Tinnitus, 141, 151, 153 Tissue, 8 Tomography, 27, 151 Tooth Preparation, 119, 151 Torsion, 135, 151 Toxic, iv, 130, 151 Toxicology, 96, 151 Transcription Factors, 12, 15, 26, 31, 151 Transduction, 12, 20, 22, 148, 151 Transfection, 20, 123, 152 Translation, 12, 152 Translocation, 72, 152 Transmitter, 121, 129, 141, 152 Transplantation, 125, 152 Tremor, 99, 152 Tuberous Sclerosis, 99, 152 Tumor suppressor gene, 146, 152 Tyrosine, 20, 129, 152 U Ubiquitin, 140, 152 Unconscious, 134, 152 Urethra, 144, 152 Urinary, 3, 54, 132, 152 Urine, 123, 133, 152 Urodynamic, 4, 152 Urogenital, 132, 152 Uterus, 125, 127, 131, 132, 152

162

Williams syndrome

V Vaccine, 144, 152 Vascular, 43, 64, 66, 69, 135, 151, 152 Vasodilator, 129, 152 Vector, 152 Vein, 141, 152 Venous, 125, 144, 153 Venous blood, 125, 153 Ventral, 12, 18, 30, 31, 32, 49, 134, 153 Ventricle, 120, 122, 130, 134, 145, 150, 151, 153 Ventricular, 17, 153 Venules, 123, 153 Vertigo, 141, 153 Vestibulocochlear Nerve, 134, 151, 153 Vestibulocochlear Nerve Diseases, 134, 151, 153

Veterinary Medicine, 95, 153 Viral, 151, 153 Virus, 122, 130, 143, 146, 152, 153 Visceral, 137, 153 Visual Cortex, 18, 28, 76, 153 Vitro, 20, 21, 27, 153 Vivo, 20, 22, 27, 153 Vocal cord, 39, 74, 153 W Weight Gain, 105, 153 White blood cell, 119, 137, 153 X Xenograft, 120, 154 X-ray, 21, 131, 141, 145, 154 Y Yeasts, 142, 154

163

164

Williams syndrome