Batten Disease: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

BATTEN DISEASE 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., 1960Batten Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00128-4 1. Batten Disease-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 batten disease. 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 BATTEN DISEASE....................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Batten Disease............................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 12 The National Library of Medicine: PubMed ................................................................................ 12 CHAPTER 2. ALTERNATIVE MEDICINE AND BATTEN DISEASE ...................................................... 33 Overview...................................................................................................................................... 33 National Center for Complementary and Alternative Medicine.................................................. 33 Additional Web Resources ........................................................................................................... 35 General References ....................................................................................................................... 36 CHAPTER 3. PERIODICALS AND NEWS ON BATTEN DISEASE ......................................................... 37 Overview...................................................................................................................................... 37 News Services and Press Releases................................................................................................ 37 Academic Periodicals covering Batten Disease ............................................................................ 38 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 43 Overview...................................................................................................................................... 43 NIH Guidelines............................................................................................................................ 43 NIH Databases............................................................................................................................. 45 Other Commercial Databases....................................................................................................... 47 APPENDIX B. PATIENT RESOURCES ................................................................................................. 49 Overview...................................................................................................................................... 49 Patient Guideline Sources............................................................................................................ 49 Associations and Batten Disease.................................................................................................. 51 Finding Associations.................................................................................................................... 52 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 55 Overview...................................................................................................................................... 55 Preparation................................................................................................................................... 55 Finding a Local Medical Library.................................................................................................. 55 Medical Libraries in the U.S. and Canada ................................................................................... 55 ONLINE GLOSSARIES.................................................................................................................. 61 Online Dictionary Directories ..................................................................................................... 61 BATTEN DISEASE DICTIONARY.............................................................................................. 63 INDEX ................................................................................................................................................ 87

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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 batten disease 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 batten disease, 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 batten disease, 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 batten disease. 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 batten disease, 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 batten disease. 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 BATTEN DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on batten disease.

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

Project Title: A DROSOPHILA MODEL OF BATTEN DISEASE Principal Investigator & Institution: Glaser, Robert L.; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The long-term objective of this research is to develop Drosophila as a model system for studying the etiology of infantile neuronal ceroid

2

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

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Batten Disease

lipofuscinosis (INCL). INCL is one of a group of related neurological diseases collectively known as Batten Disease that primarily affect infants and children. INCL, like all forms of Batten Disease, is a fatal neurodegenerative disease characterized by cytological evidence of abnormal lysosome function. INCL is caused by mutations in the palmitoyl-protein thioesterase gene (PPT1), but the molecular mechanism of neuronal pathogenesis is not known. Novel approaches to the study of INCL will help expedite the discovery of treatments for this devastating disease. The recent sequencing of the Drosophila genome has revealed that flies harbor many homologs of human disease genes, including PPT1. If mutation of Drosophila PPT1 (DmPPT1) were to recapitulate aspects of human INCL, it would provide an opportunity to investigate the etiology of INCL in a model system where extensive genetic and molecular tools are available for investigation. The goal of experiments proposed in this application is to determine if mutation to DmPPT1 in Drosophila causes neurological phenotypes characteristic of human INCL. The specific aims of the proposal are: 1. Determine the phenotypic consequences of removing DmPPT1 function by gene mutation. 2. Determine the phenotypic consequences of disrupting DmPPT1 function by RNA interference. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGICAL BASIS OF MENTAL RETARDATION Principal Investigator & Institution: Schwartz, Nancy B.; Professor of Pediatrics and Biochemistry; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-JUN-1975; Project End 31-DEC-2003 Summary: The unifying goal of this program project proposal is to define the principles governing normal nervous system developmental processes that may lead to brain dysfunction and mental retardation. The studies for the most part are basic in nature, focusing on various aspects of the cell and its environment that are involved in overall developmental processes; including examination of the extracellular matrix (ECM), cell membrane gap junctions, cytoskeletal proliferation. The derivative information from these proposed studies should define specific loci where normal developmental processes. The first project focuses on the structure and function of brain proteoglycans. The emphasis is on control of one of the major chondroitin sulfate proteoglycans (aggrecan) and elucidation of the role this important ECM component plays in neuronal development. The second project will examine intracellular communication which may play a significant role in embryonic neural development by specifically studying Connexin45, a subunit gap junction protein with special permeability properties. The third project focuses on function of NF1 protein in central nervous system neurons and astrocytes using a combination of biochemical, molecular biology and confocal microscopy techniques in tissue culture models from the chick embryos and human CNS cell lines. The fourth project is aimed toward understanding the pathogenesis of Batten disease. The aim is to develop diagnostic biochemical assays for the enzymes deficient in CLN2 (PPT) and CLN2 (endoprotease) and to determine the cause of neuronal death. A comprehensive multi-disciplinary approach using biochemical, molecular, morphologic and cell culture techniques will be used in all four projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLN3: MODULATION OF APOPTOSIS AND CERAMIDE LEVELS Principal Investigator & Institution: Boustany, Rose-Mary N.; Professor in Pediatrics and Neurobiology; Pediatrics; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007

Studies

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Summary: (provided by applicant): Long term goals are the development of rational therapies for the juvenile form of Batten disease and cancer based on the specifics of molecular, subcellular and biochemical determinants of the impact of CLN3 on apoptosis and ceramide generation. Batten disease or the Neuronal Ceroid Lipofuscinosis are a group of fatal disorders characterized by progressive cognitive and motor impairment, blindness, intractable seizures, and accelerated neuronal and photoreceptor loss. Multiple lines of evidence have converged to suggest that the defect in CLN3 causing JNCL results in apoptotic neuronal death. These are: presence of nuclear chromatin condensation by EM and evidence of DNA fragmentation by TUNEL staining of JNCL neurons, upregulation of Bcl-2 in surviving, nonapoptotic JNCL neurons, and increased ceramide levels in JNCL brain. At a cellular level, overexpression of CLN3 protein results in resistance to apoptosis induced by serum deprivation and chemotherapeutic agents, inhibition of caspase-3 activation, and a modulation of ceramide levels. Blocking CLN3 expression in human post-mitotic neurons results in spontaneous apoptosis, which was prevented by the antiapoptotic drug, flupirtine. Importantly, these antiapoptotic mechanisms also operate in cancer. There is significant over-expression of CLN3 in human and mouse cancer cell lines, and solid human colon cancer. An antisense- CLN3 adeno-virus blocks CLN3 expression in these lines, causes inhibition of cancer cell growth, increased apoptosis with loss of potential across the mitochondrial membrane, and an increase in ceramide levels. Cells derived from JNCL patients are an excellent model for the study of effects of CLN3 on apoptosis and ceramide. Overall hypothesis: the CLN3 protein impacts apoptotic pathways has a negative regulatory role in apoptosis. Specific hypotheses: a) subcellular localization(s) for this membrane protein impacts its role in apoptosis; b) motifs within CLN3 contribute to its regulatory effects on apoptosis; c) CLN3 modulates one of the steps in ceramide synthesis clearance pathways; and d) motifs within CLN3 and or CLN3 subcellular localization(s) may have an effect on ceramide levels. Specific aims include: 1) to establish the impact of CLN3 on apoptotic pathways by analyzing global gene expression; 2) to determine the determinants of CLN3 for regulating apoptosis by defining subcellular localization and CLN3 amino acids and motifs resulting in this regulation; and 3) To determine whether a step in ceramide synthesis/clearance is modulated by CLN3 by scrutinizing ceramide synthesis/clearing enzymes and metabolism in CLN3-deficient cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF LATE INFANTILE NCL Principal Investigator & Institution: Macdonald, Marcy E.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 30-APR-2005 Summary: (From Abstract) The long-term objective of this research is to understand the molecular basis of neuronal ceroid lipofuscinosis (NCL; Batten disease). NCL is the most common neurodegenerative disorder of childhood and is characterized by progressive mental deterioration, seizures, and vision loss. The hallmark of the disease is the accumulation of autofluorescent lipopigments in ultrastructural cytosomes in neurons and other cell types. Five major sub-types are now recognized on the basis of age-atonset, clinical presentation, and ultrastructural morphology: infantile (INCL), found exclusively in the Finnish population; late infantile (LNCL); juvenile (JNCL); and adult (Kufs disease). With the possible exception of the adult form, inheritance is autosomal recessive. The incidence of NCL is estimated at 1-5/100,000. Despite intensive effort, the basic biochemical defect in NCL continues to elude researchers. There is no effective

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Batten Disease

treatment for this fatal disease. The loci for the juvenile (CLN3), infantile (CLN1) types, and CLN5 have been mapped by genetic linkage analysis to chromosome 16p, 1p, and 13q respectively. The late infantile defect (CLN2) has not yet been mapped, although linkage analysis with tightly linked markers excludes it from the JNCL locus on chromosome 16 and the INCL locus on chromosome 1. The first goal of this current proposal is to use genetic linkage methods with highly polymorphic markers to localize and refine the map position of the CLN2. This information will be used to implement a positional cloning strategy for the isolation and subsequent characterization of the gene. Throughout this project period, candidate genes will be evaluated for their role in the pathogenesis of NCL by biochemical and histological studies and by our analysis of candidate JNCL genes. With the identification of closely-linked highly informative flanking markers, DNA-based pre-natal and pre-symptomatic diagnosis can be offered to at-risk families well before the actual cloning and characterization of the disease gene. The identification of mutations within the gene will allow carrier testing in selected populations. Knowledge of the molecular defect underlying LNCL will help elucidate the biochemical pathways involved in the pathogenesis of the disease, shed light on the possible cause of the other ceroid lipofuscinoses, and provide a starting point for the design of rational therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PATHOGENIC DISSECTION OF BATTEN DISEASE Principal Investigator & Institution: Zhong, Nanbert; Director; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, Ny 10314 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant):The broad, long-term objectives of our studies of Batten disease (BD), the juvenile form of neuronal ceroid lipofuscinosis (NCL), are to understand its molecular pathogenic mechanisms and thus contribute to development of a rational therapy. We have hypothesized that: 1) a common metabolic pathway is involved in the pathophysiology of a NCL including BD, and 2) the pathway is composed of CLN-encoded lysosomal proteinases and a novel transmembrane protein complex that comprises CLN-encoded proteins including CLN3-encoded Battenin, CLN5-encoded CLN5p, CLN6-encoded CLN6p, and CLN8-encoded CLN8p, as well as other unknown protein(s). The specific goal of this application is to study the molecular pathogenic mechanisms of BD by testing our working hypothesis that fast Battenininteractive protein (BIPf), a transmembrane protein recently identified in our laboratory, may be involved in BD. BIPf is found to interact not only with Battenin and CLN8p, the normal proteins encoded by the genes CLN3 and CLN8, respectively, but also with the mutant Battenin via an increased interactive affinity and with the mutant CLN8pm via a decreased interactive affinity, as well as with mitochondrial ATP synthase (ATPase) subunit C. In addition, our preliminary data suggested that battenim alters the antiapoptotic function of BIPf, which is also known as a Bax inhibitor (BI-1), and causes programmed neuronal death in BD. To achieve our goal, four specific aims will be pursued: (1) to explore BIPf interaction with the CLN5-and CLN6-encoded membranespanning proteins CLN5p and CLN6p, in addition to CLN6-encoded CLN8p, with the yeast and mammalian two-hybrid systems and immunoprecipitation/pull-down approaches; (2) to characterize the functional relationship of BIPf to BD by determining differential interactions of "gain/loss-of-affinity" between BIPf and mutant CLNencoded proteins; (3) to assess the possible roles of BIPf in the pathogenic pathway of BD by testing whether BIPf medicates the pathological accumulation of mitochondrial ATPase subunit C; and (4) to study the regulatory effects of Battenim on the anti-

Studies

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apoptotic function of BIPf in BD. The results of this investigation will lead to a better understanding of the molecular mechanisms underlying the pathogenesis of BD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURON CULTURES FOR CLN6 BATTEN DISEASE STUDIES Principal Investigator & Institution: Palmer, David N.; Lincoln University Canterbury, New Zealand Canterbury, Timing: Fiscal Year 2002; Project Start 08-SEP-2000; Project End 31-AUG-2003 Summary: (application abstract): The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited pediatric neurodegenerative diseases. The aim of this application is to exploit neuron cultures developed from an ovine model as an in vitro model of human disease and use it, in combination with whole animal studies, to study the mechanism of neurodegeneration and explore possible therapies. The NCLs are characterized by profound neurodegeneration and the intracellular accumulation of subunit c of mitochondrial ATP synthase. Cortical neuronal cultures have been established from affected sheep and storage body accumulation observed in cultured cells. This investigation will optimize these neuron Cultures as a model of the in situ pathology. The mechanism of neurodegeneration will be studied in them. Specific hypotheses to be tested are that subunit c storage is directly related to neurodegeneration, that a disruption in the endosome-lysosome pathway is central to the neurodegeneration and that accumulation of subunit c results in over-activity of an oligomeric subunit c ionpore in the neuronal plasma membrane. The role of apoptosis and excitotoxicity will be examined and the efficacy of IGF1 and other growth factors that might overcome neurodegeneration tested. Chimeric normal/affected sheep will be generated to delineate the possibilities for gene and enzyme therapy. The clinical course of disease will be monitored in affected sheep transgenically overexpressing IGF1 in brain, to determine if this ameliorates the development of symptoms. Possible therapies will be tested in whole animal experiments. Results will be relevant to understanding the pathobiology of the NCLs and will test the likelihood of benefits of possible treatments. Findings will also be relevant to understanding other protein storing neurodegenerative diseases, such as Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEURONAL LIPOFUSCINOSIS

DEGENERATION

HEREDITARY

CEROID-

Principal Investigator & Institution: Katz, Martin L.; Ophthalmology; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from applicant's abstract): Juvenile ceroid-lipofuscinosis (Batten disease, CLN3) is one of the most common hereditary neurodegenerative disorders. It is inherited as an autosomal-recessive trait. Blindness due to retinal degeneration is usually the first clinical symptom, with complete vision loss occurring between the ages of 5 and 7 years. Subsequently, affected individuals develop seizures, and undergo psychomotor and cognitive deterioration to a vegetative state. Death usually occurs in the late teenage years to the twenties. The severe and progressive nature of this disease results in enormous medical, financial, and emotional burdens on families with afflicted children. Little is known regarding the etiology of Batten disease, and no effective treatments have been developed. A distinctive biochemical feature of this disorder is a massive intracellular accumulation of autofluorescent lysosomal storage bodies in most

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Batten Disease

tissues. The subunit c protein of mitochondrial ATP synthase is a major constituent of the storage bodies. The overall goals of the proposed research are to determine the molecular mechanisms responsible for the lysosomal storage of the subunit c protein, and to develop treatments that will prevent or slow the progressive neuronal degeneration that leads to blindness and cognitive decline. To accomplish these goals, experiments will be conducted to achieve the following specific aims: (1) complete phenotypic characterization of a mouse "gene knock-out" model for juvenile ceroidlipofuscinosis; (2) determine whether carnitine supplements can slow disease progression in mice in which the CLN3 gene has been inactivated (knocked out); (3) evaluate the potential of neuroprotectants to prevent neural degeneration in mice in which the CLN3 gene has been knocked out; (4) purify and characterize the CLN3 protein; and (5) determine whether the rates of subunit c protein synthesis and/or degradation are altered in juvenile ceroid-lipofuscinosis and in tissues of CLN3 knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL LYSOSOMAL ENZYME DEFICIENT IN BATTEN DISEASE Principal Investigator & Institution: Lobel, Peter; Professor; Pharmacology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: This is a project to determine the molecular basis of the late infantile form of neuronal ceroid lipofuscinosis (LINCL). The starting point is the successful cloning of the cDNA and determination of mutations in the CLN2 protein. The specific aims are to (1) determine the structure of the gene; (2) Identify mutations in the CLN2 gene; (3) develop a mouse model of the disease; and (4) characterize the CLN2 protein and its function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PALMITOYL PROTEIN THIOESTERASE Principal Investigator & Institution: Hofmann, Sandra L.; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAY-2004 Summary: (Adapted from the applicant's abstract): Infantile neuronal ceroid lipofuscinosis or INCL is a devastating genetically inherited disease caused by a deficiency in palmitoyl-protein thioesterase or PPT1. The hallmarks of the disease are rapid neurologic decline, seizures and blindness due to massive neuronal and retinal cell loss leading to an isoelectric EEG and early death. In this competitive renewal the investigator proposes to do the following. (1) The major metabolic products accumulating in cells from patients with the infantile form of Batten disease will be identified. The investigator states that lipid thioesters derived from acylated proteins accumulate in this disease and that they are neurotoxic. (2) Substrate specificities of PPT1 and PPT2 will be explored based on three-dimensional structure as determined by X-ray crystallography. (3) A circulating inhibitor of PPT1 and PPT2 will be purified from human plasma, then characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

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Project Title: PALMITOYL DEVELOPMENT

PROTEIN

THIOESTERASES

IN

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NEURAL

Principal Investigator & Institution: Chu-Lagraff, Quynh; Biological Sciences; Union College 807 Union St Schenectady, Ny 12308 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): The research goal is to investigate the biological roles of the Drosophila genes Palmitoyl Protein Thioesterase I and 2 (Ppt1 and Ppt2) in the developing and adult nervous system to facilitate the understanding of the pathogenesis of infantile neuronal ceroid lipofuscinosis (INCL). INCL belongs to the class of pediatric neurological disorder collectively called Batten Disease. Defects in human PPT1 lead to INCL, which is characterized by autofluorescent lipopigment inclusions, abnormal lysosomal function, extensive neuronal cell death in the developing brain, degeneration of cognitive, motor and visual functions, and premature death. Loss of PPT2 in mice also leads to similar characteristics including reduced brain size, extensive motor and neuronal degeneration, and lipopigment accumulation. PPT1 and PPT2 proteins reside in the lysosome and catalyze the removal of palmitoylated fatty acids attached to the cysteine residue of lipid-modified proteins. Although both proteins have comparable thioesterase activity in vitro, PPT2 cannot rescue the metabolic defects caused by loss of PPT1. In spite of molecular identification, studies identifying the underlying INCL pathological mechanism are limited by poor understanding of PPT1 and PPT2 normal functions. Relatively little is known about the basic biology of either lysosomal proteins, and how defective palmitoyl-protein thioesterases lead to neurotoxicity and degeneration. A fundamental understanding of Ppt1 and Ppt2 and their basic biology in a genetically tractable model system is essential. Previously we have shown that Drosophila Ppt1 exhibits Ppt1-specific enzyme activity and is likely to be the fly version of PPTI. Drosophila also contains a homologous PPT2 protein, Ppt2. We plan to (1) identify the spatial, temporal, and subcellular expression profile of Ppt1 and Ppt2 transcripts and proteins during development and adult; (2) generate Ppt2 loss-of-function mutations by P-element excision mutagenesis; and (3) analyze Ppt2 mutants and compare it to existing Ppt1 mutants at the molecular, cellular, genetic, and behavioral level. These results will allow us to generate a working model for how these proteins regulate neuronal development and maintenance, protein turnover, and intracellular trafficking. Such information may provide insight into the mechanisms of pathogenesis by identifying potential elements that are compromised in Batten Diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF BATTEN DISEASE Principal Investigator & Institution: Dawson, Glyn; Professor; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002 Summary: This project is aimed at understanding the biochemical pathology of Batten disease (a devastating mental retardation syndrome), using lymphoblastoid cell lines and fibroblast cultures from patients and neural tissues cultures similar to those used in the other projects. In the infantile form (CLN1) we will focus on the substrate specificity on the defective palmitoyl: protein thioesterase, the storage material and the source of this storage material from neural membrane turnover. In the late infantile form (CLN2) we will focus on the substrate specificity of the defective pepstatin-insensitive carboxyl peptidase, the storage material and its source, and in the juvenile form (CLN3) we will

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focus on the possible role of the protein gene product in facilitating proteolysis in the lysosome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOPHYSIOLOGY AND NOVEL THERAPIES FOR BATTEN'S DISEASE Principal Investigator & Institution: Sands, Mark S.; Associate Professor; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2006 Summary: (provided by applicant): Neuronal Ceroid Lipofuscinoses (NCL, Batten Disease) are inherited neurodegenerative diseases primarily affecting children. One hallmark of the NCLs is that accumulation of autofluorescent material in the lysosomes of many cell types including neurons of the brain. Children with NCL suffer from blindness, seizures, motor and mental deterioration and premature death. The earliest form of NCL, Infantile Neuronal Ceroid Lipofuscinosis (INCL), is caused by a deficiency in the soluble lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1) and is, therefore, classified as a lysosomal storage disease. Currently, there is no effective treatment for INCL. We recently obtained a newly developed mouse model of PPT1 deficiency. Although very little is known yet about the disease progression in this model, it is completely deficient in PPT1 activity and autofluorescent material accumulates in neurons of the brain. These two characteristics alone make this a valuable small animal model to study the disease progression and develop novel therapeutic approaches. It was recently shown in a murine model of another lysosomal storage disease that direct intracranial injection of agene transfer vector could reduce the accumulation of lysosomal storage in the brain and improve cognitive function. Due to the biochemical similarities between many lysosomal enzymes, we believe that a gene therapy approach using recombinant viral vectors may also prove efficacious for INCL. The long-term goals of this research are to determine the effects of PPT1 deficiency on visual and cognitive functions in the mouse and then evaluate the efficacy of viralmediated gene transfer in correcting the enzyme deficiency and preserving these functions. We will accomplish these goals with the following specific aims: 1. We wil create and characterize in vitro recombinant AAV and lentiviral gone transfer vectors encoding human palmitoyl protein thioesterase-1 (PPT1). 2. We will determine the progression and extent of clinical disease, especially the retinal and cognitive dysfunction in the PPTl-deficient mouse. 3. We will determine the efficacy of viralmediated gene therapy approaches for INCL in the PPT1 deficient mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STEM CELL THERAPIES FOR BATTEN DISEASE Principal Investigator & Institution: Kirk, Mark D.; Biological Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term goal of our research is to develop therapeutic applications for stem cell transplantation to treat hereditary neurodegenerative diseases. Our emphasis is on the neuronal ceroid-lipofuscinoses (NCLs). The NCLs are a group of inherited, progressive degenerative disorders of childhood characterized by loss of nerve cells in the retina and central nervous system (CNS). One NCL is commonly known as Batten Disease. The focus of this proposal is on degeneration in the retina, but our results will be applicable to degeneration

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throughout the CNS. We will transplant neuralized mouse embryonic stem (ES) cells that express enhanced green fluorescent protein (EGFP; for cell tracing) into the eyes of mouse models for NCLs. Our primary hypothesis is that transplantation of specifically engineered, neural-induced ES cells will retard or prevent retinal degeneration resulting in visual recovery. To test our hypothesis, the following specific aims will be performed. Specific Aim #1 is to induce (neuralize) and transplant ES cells into host eyes and assess stem cell survival and integration within the retina. After induction, the ES cells will be injected into the eyes of mutant mice, and the fate of transplanted cells will be evaluated with antibodies specific for neural and glial markers. Specific Aim #2 is to test in vitro for cross-correction of the cellular phenotype, due to factors secreted by donor ES cells. To promote survival of host neurons, ES cells will be engineered to express a growth factor (IGF-1) or the normal enzyme that is mutated in the Clnl mutant mouse. Use of a CMV promoter will ensure over-expression of the genes by neuralized ES cells. Specific Aim #3 is to assess transplanted cell function and whether host retinal cells exhibit enhanced survival after stem cell transplantation. To determine if a normal ultrastructural phenotype is restored in host retinal cells and whether cellular connections are established between transplanted stem cells and host retinal cells immunoelectron microscopy (using an EGFP antibody), and electrophysiology will be performed. We will use electroretinograms to test for maintenance and/or recovery of visual function, intracellular recordings and dye-injections in retinal slice preparations will be used to determine the functional fates of donor cells as well as that of host cells. This research will provide essential new information about the use of stem cells in potential therapies for the NCLs as well as for other inherited neurodegenerative disorders of the CNS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE AUTOIMMUNE RESPONSE IN BATTEN DISEASE Principal Investigator & Institution: Pearce, David A.; Associate Professor; Biochemistry and Biophysics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Batten, with an incidence as high as one in 12,500 live births. Batten disease results from mutation of CLN3, and is characterized pathologically by the accumulation of autofluorescent hydrophobic material in the lysosome of neurons and other cell types. However, the mechanism driving these cellular alterations and the manner in which they relate to the neurodegeneration in Batten disease is unknown. Individuals with Batten disease, and a cln3-knockout mouse model for Batten disease have a circulating autoantibody to glutamic acid decarboxylase (GAD65) that is inhibitory to this enzyme's ability to convert glutamic acid to 7-aminobutyric acid (GABA). The GAD65 autoantibody associates with the brain in cln3-knockout mice, inhibits the activity of GAD, and results in a subsequent elevation of glutamate and altered expression of genes involved in the regulation and utilization of glutamate. The major goal of this proposal is to establish and characterize the contribution of the GAD65 autoantibody to the pathogenesis of Batten disease. As the model for this study is a genetically defined I knockout mouse, we will establish whether the presence of a GAD65 autoantibody is simply an epiphenomenon, and whether it contributes directly to Batten disease. We shall: (i) construct cln3-knockout mice that are unable to mount an immune response to GAD65 by crossing to MuMT and C-alpha knockout mice, which lack the ability to generate B-cells, and CD4+ and CD8+ T-cells, respectively. This will enable us to determine whether the autoantibody contributes to the pathology of Batten disease. (ii) test by passive transfer of GAD65

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autoantibodies to normal mice the degree of pathogenicity on the CNS mediated by these autoantibodies. Also, by transfer of GAD65 autoantibodies to immune deficient mice we will determine if the cln3-defect allows for preferential deposition of IgG in the brain (iii) define the inflammatory response to the presence of autoantibodies and the participation of the innate immune system in the disease process in cln3-knockout mice by examining cytokines such as IL-1 and TNF, complement proteins and microglial activation, respectively. (iv) characterize cell type specific molecular effects that elevated glutamate and exposure to the autoantibody have on primary neuronal culture from cln3-knockout mice. 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 “batten disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for batten disease in the PubMed Central database: •

Two Motifs Target Batten Disease Protein CLN3 to Lysosomes in Transfected Nonneuronal and Neuronal Cells. by Kyttala A, Ihrke G, Vesa J, Schell MJ, Luzio JP.; 2004 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=363135

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 batten disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “batten disease” (or 3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for batten disease (hyperlinks lead to article summaries): •

A disrupted homologue of the human CLN3 or juvenile neuronal ceroid lipofuscinosis gene in Saccharomyces cerevisiae: a model to study Batten disease. Author(s): Guo WX, Mao C, Obeid LM, Boustany RM. Source: Cellular and Molecular Neurobiology. 1999 October; 19(5): 671-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10384264

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A form of juvenile Batten disease with granular osmiophilic deposits. Author(s): Lake BD, Brett EM, Boyd SG. Source: Neuropediatrics. 1996 October; 27(5): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971748

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A model for Batten disease protein CLN3: functional implications from homology and mutations. Author(s): Janes RW, Munroe PB, Mitchison HM, Gardiner RM, Mole SE, Wallace BA. Source: Febs Letters. 1996 December 9; 399(1-2): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8980123

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A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease. Author(s): Kim Y, Ramirez-Montealegre D, Pearce DA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 December 23; 100(26): 15458-62. Epub 2003 Dec 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660799

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A yeast model for the study of Batten disease. Author(s): Pearce DA, Sherman F. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 June 9; 95(12): 6915-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9618513

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Abnormal cathepsin B activity in Batten disease. Author(s): Dawson G, Glaser PT. Source: Am J Med Genet Suppl. 1988; 5: 209-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146318

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Abnormal degradative pathway of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Ezaki J, Wolfe LS, Ishidoh K, Kominami E. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 254-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668341

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Abnormal lysosomal cathepsin activities in leukocytes and cultured skin fibroblasts in late infantile, but not in juvenile neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Bennett MJ, Chern L, Carpenter KH, Sladky JT. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1992 June 15; 208(1-2): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1638746

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Accumulation of dolichol-linked oligosaccharides in ceroid-lipofuscinosis (Batten disease). Author(s): Hall NA, Patrick AD. Source: Am J Med Genet Suppl. 1988; 5: 221-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146320

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Accumulation of phosphorylated dolichol in several tissues in ceroid-lipofuscinosis (Batten disease). Author(s): Hall NA, Patrick AD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1987 December; 170(2-3): 323-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3436065

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Action of BTN1, the yeast orthologue of the gene mutated in Batten disease. Author(s): Pearce DA, Ferea T, Nosel SA, Das B, Sherman F. Source: Nature Genetics. 1999 May; 22(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319861

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An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease. Author(s): Chattopadhyay S, Ito M, Cooper JD, Brooks AI, Curran TM, Powers JM, Pearce DA. Source: Human Molecular Genetics. 2002 June 1; 11(12): 1421-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023984

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Analysis of Batten disease candidate genes STP and STM. Author(s): Munroe PB, Mitchison HM, Dooley TP, Gardiner RM, Mole SE. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 324-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668356

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Batten disease (Spielmeyer-Sjogren disease) and haptoglobins (HP): indication of linkage and assignment to chr. 16. Author(s): Eiberg H, Gardiner RM, Mohr J. Source: Clinical Genetics. 1989 October; 36(4): 217-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2805379

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Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroidlipofuscinosis) gene (CLN3) maps to human chromosome 16. Author(s): Gardiner M, Sandford A, Deadman M, Poulton J, Cookson W, Reeders S, Jokiaho I, Peltonen L, Eiberg H, Julier C. Source: Genomics. 1990 October; 8(2): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2249854

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Batten disease and mitochondrial pathways of proteolysis. Author(s): Tanner AJ, Dice JF. Source: Biochemical and Molecular Medicine. 1996 February; 57(1): 1-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8812718

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Batten disease and the ATP synthase subunit c turnover pathway: raising antibodies to subunit c. Author(s): Palmer DN, Bayliss SL, Westlake VJ. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 260-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668342

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Batten disease fibroblasts in culture accumulate mitochondrial ATP synthase subunit 9. Author(s): Tanner A, Dice JF. Source: Cell Biology International. 1995 January; 19(1): 71-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7613514

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Batten disease gene, CLN3: linkage disequilibrium mapping in the Finnish population, and analysis of European haplotypes. Author(s): Mitchison HM, O'Rawe AM, Taschner PE, Sandkuijl LA, Santavuori P, de Vos N, Breuning MH, Mole SE, Gardiner RM, Jarvela IE. Source: American Journal of Human Genetics. 1995 March; 56(3): 654-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7887419

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Batten disease in the west of Scotland 1974-1995 including five cases of the juvenile form with granular osmiophilic deposits. Author(s): Crow YJ, Tolmie JL, Howatson AG, Patrick WJ, Stephenson JB. Source: Neuropediatrics. 1997 June; 28(3): 140-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9266550

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Batten disease research--where we were--where we are--where we are going. Author(s): Rider JA, Rider DL. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5 Suppl A: 3-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589003

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Batten disease, a twenty-eight-year struggle: past, present and future. Author(s): Rider JA, Rider DL. Source: Neuropediatrics. 1997 February; 28(1): 4-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151308

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Batten disease: evaluation of CLN3 mutations on protein localization and function. Author(s): Haskell RE, Carr CJ, Pearce DA, Bennett MJ, Davidson BL. Source: Human Molecular Genetics. 2000 March 22; 9(5): 735-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10749980

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Batten disease: four genes and still counting. Author(s): Mole SE. Source: Neurobiology of Disease. 1998 November; 5(5): 287-303. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069573

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Batten disease: new research findings on the biochemical defect. Author(s): Wolfe LS, Ng Ying Kin NM. Source: Birth Defects Orig Artic Ser. 1982; 18(6): 233-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7171758

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Batten disease: ocular features, differential diagnosis and diagnosis by enzyme analysis. Author(s): Zeman W. Source: Birth Defects Orig Artic Ser. 1976; 12(3): 441-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=782600

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Batten disease: past, present, and future. Author(s): Rider JA, Rider DL. Source: Am J Med Genet Suppl. 1988; 5: 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146319

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Batten disease--an overview of research and funding. Author(s): Rider JA. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668315

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Batten disease--deteriorating course of ocular findings. Author(s): Horiguchi M, Miyake Y. Source: Japanese Journal of Ophthalmology. 1992; 36(1): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1635301

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Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease. Author(s): Jarvela I, Sainio M, Rantamaki T, Olkkonen VM, Carpen O, Peltonen L, Jalanko A. Source: Human Molecular Genetics. 1998 January; 7(1): 85-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9384607

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Bone marrow transplantation in Batten disease (neuronal ceroid-lipofuscinosis). Will it work? Preliminary studies on coculture experiments and on bone marrow transplant in late infantile Batten disease. Author(s): Lake BD, Henderson DC, Oakhill A, Vellodi A. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 369-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668365

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Bone marrow transplantation in late infantile Batten disease and juvenile Batten disease. Author(s): Lake BD, Steward CG, Oakhill A, Wilson J, Perham TG. Source: Neuropediatrics. 1997 February; 28(1): 80-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151332

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Carrier detection of Batten disease (juvenile neuronal ceroid-lipofuscinosis). Author(s): Taschner PE, de Vos N, Post JG, Meijers-Heijboer EJ, Hofman I, Loonen MC, Pinckers AJ, Bleeker-Wagemakers EM, Gardiner RM, Breuning MH. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668358

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Cellular distribution of lesions in Batten disease. Author(s): Chronister R, Dyken P, Fields PA, Maertens P. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668329

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Ceroid, lipofuscin and the ceroid-lipofuscinoses (Batten disease). Author(s): Jolly RD, Dalefield RR, Palmer DN. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 280-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411981

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Ceroid-lipofuscinosis (Batten disease). Fluorescein angiography, electrophysiology, histopathology, ultrastructure, and a review of amaurotic familial idiocy. Author(s): Hittner HM, Ziller RS. Source: Archives of Ophthalmology. 1975 March; 93(3): 178-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1138683

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Chromosome 16 microdeletion in a patient with juvenile neuronal ceroid lipofuscinosis (Batten disease). Author(s): Taschner PE, de Vos N, Thompson AD, Callen DF, Doggett N, Mole SE, Dooley TP, Barth PG, Breuning MH. Source: American Journal of Human Genetics. 1995 March; 56(3): 663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7887420

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Clinical and magnetic resonance imaging findings in Batten disease: analysis of the major mutation (1.02-kb deletion). Author(s): Jarvela I, Autti T, Lamminranta S, Aberg L, Raininko R, Santavuori P. Source: Annals of Neurology. 1997 November; 42(5): 799-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9392580

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CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease. Author(s): Luiro K, Kopra O, Lehtovirta M, Jalanko A. Source: Human Molecular Genetics. 2001 September 15; 10(19): 2123-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590129

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Coding sequence and exon/intron organization of the canine CLN3 (Batten disease) gene and its exclusion as the locus for ceroid-lipofuscinosis in English setter dogs. Author(s): Shibuya H, Liu PC, Katz ML, Siakotos AN, Nonneman DJ, Johnson GS. Source: Journal of Neuroscience Research. 1998 May 1; 52(3): 268-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590435

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Decreased erythrocyte and platelet phospholipids and fatty acids in juvenile neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Bennett MJ, Galloway JH, Cartwright IJ, Gillis WS, Hosking GP. Source: Neuropediatrics. 1990 November; 21(4): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2290481

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Decreased plasma carnitine and trimethyl-L-lysine levels associated with lysosomal accumulation of a trimethyl-L-lysine containing protein in Batten disease. Author(s): Katz ML. Source: Biochimica Et Biophysica Acta. 1996 December 16; 1317(3): 192-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8988235

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Defective intracellular transport of CLN3 is the molecular basis of Batten disease (JNCL) Author(s): Jarvela I, Lehtovirta M, Tikkanen R, Kyttala A, Jalanko A. Source: Human Molecular Genetics. 1999 June; 8(6): 1091-8. Erratum In: Hum Mol Genet 1999 August; 8(8): 1585. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332042

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Delivery of liposome-sequestered hydrophobic proteins to lysosomes of normal and Batten disease cells. Author(s): Ansari NH, He Q, Cook JD, Wen J, Srivastava SK. Source: Journal of Neuroscience Research. 1997 February 1; 47(3): 341-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039656

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Diagnosis of Batten disease from urinary sediment: a brief report. Author(s): Armstrong D, Wehling C, Wormer DV. Source: Pathology. 1977 January; 9(1): 39-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=854361

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Different patterns of hydrophobic protein storage in different forms of neuronal ceroid lipofuscinosis (NCL, Batten disease). Author(s): Palmer DN, Jolly RD, van Mil HC, Tyynela J, Westlake VJ. Source: Neuropediatrics. 1997 February; 28(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151321

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Distribution of apolipoprotein E genotypes in fragile X syndrome and Batten disease. Author(s): Zhong N, Ju W, Brown WT, Ye L, Jenkins EC, Schupf N. Source: American Journal of Medical Genetics. 1999 May 28; 84(3): 309-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10331615

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Early changes in gene expression in two models of Batten disease. Author(s): Elshatory Y, Brooks AI, Chattopadhyay S, Curran TM, Gupta P, Ramalingam V, Hofmann SL, Pearce DA. Source: Febs Letters. 2003 March 13; 538(1-3): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633880

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Evidence for phosphorylation of CLN3 protein associated with Batten disease. Author(s): Michalewski MP, Kaczmarski W, Golabek AA, Kida E, Kaczmarski A, Wisniewski KE. Source: Biochemical and Biophysical Research Communications. 1998 December 18; 253(2): 458-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9878558

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Farnesylation of Batten disease CLN3 protein. Author(s): Pullarkat RK, Morris GN. Source: Neuropediatrics. 1997 February; 28(1): 42-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151320

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Fine genetic mapping of the Batten disease locus (CLN3) by haplotype analysis and demonstration of allelic association with chromosome 16p microsatellite loci. Author(s): Mitchison HM, Thompson AD, Mulley JC, Kozman HM, Richards RI, Callen DF, Stallings RL, Doggett NA, Attwood J, McKay TR, et al. Source: Genomics. 1993 May; 16(2): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8314582

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Follow-up study of subunit c of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. Author(s): Elleder M, Sokolova J, Hrebicek M. Source: Acta Neuropathologica. 1997 April; 93(4): 379-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9113203

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Functional categorization of gene expression changes in the cerebellum of a Cln3knockout mouse model for Batten disease. Author(s): Brooks AI, Chattopadhyay S, Mitchison HM, Nussbaum RL, Pearce DA. Source: Molecular Genetics and Metabolism. 2003 January; 78(1): 17-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559844

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Genetic analysis of Batten disease. Author(s): Gardiner RM. Source: Journal of Inherited Metabolic Disease. 1993; 16(4): 787-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412021

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Genetic mapping of the Batten disease locus (CLN3) to the interval D16S288-D16S383 by analysis of haplotypes and allelic association. Author(s): Mitchison HM, Taschner PE, O'Rawe AM, de Vos N, Phillips HA, Thompson AD, Kozman HM, Haines JL, Schlumpf K, D'Arigo K, et al. Source: Genomics. 1994 July 15; 22(2): 465-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7806237

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Genomic structure and complete nucleotide sequence of the Batten disease gene, CLN3. Author(s): Mitchison HM, Munroe PB, O'Rawe AM, Taschner PE, de Vos N, Kremmidiotis G, Lensink I, Munk AC, D'Arigo KL, Anderson JW, Lerner TJ, Moyzis RK, Callen DF, Breuning MH, Doggett NA, Gardiner RM, Mole SE. Source: Genomics. 1997 March 1; 40(2): 346-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9119403

Studies

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Histopathologic and immunocytochemical analysis of the retina and ocular tissues in Batten disease. Author(s): Bensaoula T, Shibuya H, Katz ML, Smith JE, Johnson GS, John SK, Milam AH. Source: Ophthalmology. 2000 September; 107(9): 1746-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10964839

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Human forms of neuronal ceroid-lipofuscinosis (Batten disease): consensus on diagnostic criteria, Hamburg 1992. Author(s): Kohlschutter A, Gardiner RM, Goebel HH. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 241-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411970

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Identification of retinoyl complexes as the autofluorescent component of the neuronal storage material in Batten disease. Author(s): Wolfe LS, Kin NM, Baker RR, Carpenter S, Andermann F. Source: Science. 1977 March 25; 195(4284): 1360-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=841336

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Immunochemical localization of the Batten disease (CLN3) protein in retina. Author(s): Katz ML, Gao CL, Prabhakaram M, Shibuya H, Liu PC, Johnson GS. Source: Investigative Ophthalmology & Visual Science. 1997 October; 38(11): 2375-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9344361

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Immunocytochemical studies in the ceroid-lipofuscinoses (Batten disease) using antibodies to subunit c of mitochondrial ATP synthase. Author(s): Westlake VJ, Jolly RD, Bayliss SL, Palmer DN. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668326

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Immunolocalization studies of subunit c in late-infantile and juvenile Batten disease. Author(s): Lake BD, Hall NA. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 263-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411976

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Immunoreactivity of ceroid lipofuscin storage pigment in Batten disease with monoclonal antibodies to the amyloid beta-protein. Author(s): Wisniewski KE, Maslinska D. Source: The New England Journal of Medicine. 1989 January 26; 320(4): 256-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2911317

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Batten Disease

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Incidence of neuronal perikaryal spheroids in neuronal ceroid lipofuscinoses (Batten disease). Author(s): Elleder M, Tyynela J. Source: Clin Neuropathol. 1998 July-August; 17(4): 184-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9707331

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Infantile neuronal ceroid-lipofuscinosis is not an allelic form of Batten disease: exclusion of chromosome 16 region with linkage analyses. Author(s): Jokiaho I, Puhakka L, Santavuori P, Manninen T, Nyman K, Peltonen L. Source: Genomics. 1990 October; 8(2): 391-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2249855

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Intracellular trafficking of CLN3, the protein underlying the childhood neurodegenerative disease, Batten disease. Author(s): Mao Q, Xia H, Davidson BL. Source: Febs Letters. 2003 December 4; 555(2): 351-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644441

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Investigation of Batten disease with the yeast Saccharomyces cerevisiae. Author(s): Pearce DA, Sherman F. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 314-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191120

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Ion pores made of mitochondrial ATP synthase subunit c in the neuronal plasma membrane and Batten disease. Author(s): McGeoch JE, Palmer DN. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 387-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191134

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Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3. Author(s): Lee RL, Johnson KR, Lerner TJ. Source: Genomics. 1996 August 1; 35(3): 617-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8812504

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Isolation of genes from the Batten candidate region using exon amplification. Batten Disease Consortium. Author(s): Lerner TJ, D'Arigo KL, Haines JL, Doggett NA, Taschner PE, de Vos N, Buckler AJ. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 320-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668355

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Late-infantile Batten disease: purification of the subunit c of the mitochondrial ATP synthase from storage material. Author(s): Hagopian K, Lake BD, Winchester BG, Clark JB. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 272-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668344

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Lectin histochemistry in brains with juvenile form of neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Wisniewski KE, Maslinska D. Source: Acta Neuropathologica. 1990; 80(3): 274-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2399809

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Letter: Batten disease. Author(s): Armstrong D. Source: Archives of Neurology. 1974 July; 31(1): 69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4834547

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Light and electron microscopic studies on subunit c in cultured fibroblasts in late infantile and juvenile Batten disease. Author(s): Lake BD, Rowan SA. Source: Neuropediatrics. 1997 February; 28(1): 56-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151324

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Localization and processing of CLN3, the protein associated to Batten disease: where is it and what does it do? Author(s): Pearce DA. Source: Journal of Neuroscience Research. 2000 January 1; 59(1): 19-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10658181

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Lysosomal proteinosis based on decreased degradation of a specific protein, mitochondrial ATP synthase subunit C: Batten disease. Author(s): Ezaki J, Wolfe LS, Ishidoh K, Muno D, Ueno T, Kominami E. Source: Advances in Experimental Medicine and Biology. 1996; 389: 121-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8861001

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Mapping of two phenol sulphotransferase genes, STP and STM, to 16p: candidate genes for Batten disease. Author(s): Dooley TP, Mitchison HM, Munroe PB, Probst P, Neal M, Siciliano MJ, Deng Z, Doggett NA, Callen DF, Gardiner RM, et al. Source: Biochemical and Biophysical Research Communications. 1994 November 30; 205(1): 482-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7999068

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Batten Disease

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Membrane topology of CLN3, the protein underlying Batten disease. Author(s): Mao Q, Foster BJ, Xia H, Davidson BL. Source: Febs Letters. 2003 April 24; 541(1-3): 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706816

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Mitochondrial abnormalities in CLN2 and CLN3 forms of Batten disease. Author(s): Dawson G, Kilkus J, Siakotos AN, Singh I. Source: Mol Chem Neuropathol. 1996 October-December; 29(2-3): 227-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8971698

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Mitochondrial ATP synthase subunit c storage in the ceroid-lipofuscinoses (Batten disease). Author(s): Palmer DN, Fearnley IM, Walker JE, Hall NA, Lake BD, Wolfe LS, Haltia M, Martinus RD, Jolly RD. Source: American Journal of Medical Genetics. 1992 February 15; 42(4): 561-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1535179

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Mitochondrial damage results in a reversible increase in lysosomal storage material in lymphoblasts from patients with juvenile neuronal ceroid-lipofuscinosis (Batten Disease). Author(s): Boriack RL, Cortinas E, Bennett MJ. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668350

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Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease). Author(s): Jolly RD, Brown S, Das AM, Walkley SU. Source: Neurochemistry International. 2002 May; 40(6): 565-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850114

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Molecular screening of Batten disease: identification of a missense mutation (E295K) in the CLN3 gene. Author(s): Zhong N, Wisniewski KE, Kaczmarski AL, Ju W, Xu WM, Xu WW, Mclendon L, Liu B, Kaczmarski W, Sklower Brooks SS, Brown WT. Source: Human Genetics. 1998 January; 102(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9490299

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Morphological approaches to the prenatal diagnosis of late-infantile and juvenile Batten disease. Author(s): Lake BD. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 345-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411995

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Neurodegenerative disease: the neuronal ceroid lipofuscinoses (Batten disease). Author(s): Mitchison HM, Mole SE. Source: Current Opinion in Neurology. 2001 December; 14(6): 795-803. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11723391

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New insight into lysosomal protein storage disease: delayed catabolism of ATP synthase subunit c in Batten disease. Author(s): Kominami E, Ezaki J, Wolfe LS. Source: Neurochemical Research. 1995 November; 20(11): 1305-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786816

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Pathogenesis of brain dysfunction in Batten disease. Author(s): Walkley SU, March PA, Schroeder CE, Wurzelmann S, Jolly RD. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 196-203. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668330

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Phenol sulfotransferases: candidate genes for Batten disease. Author(s): Dooley TP, Probst P, Obermoeller RD, Siciliano MJ, Doggett NA, Callen DF, Mitchison HM, Mole SE. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 327-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668357

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Phenotypic reversal of the btn1 defects in yeast by chloroquine: a yeast model for Batten disease. Author(s): Pearce DA, Carr CJ, Das B, Sherman F. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 September 28; 96(20): 11341-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10500178

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Phospholipases and the molecular basis for the formation of ceroid in Batten disease. Author(s): Dawson G, Dawson SA, Siakotos AN. Source: Advances in Experimental Medicine and Biology. 1989; 266: 259-70; Discussion 271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2486153

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Physical map of the region containing the gene for Batten disease (CLN3). Author(s): Jarvela IE, Mitchison HM, Callen DF, Lerner TJ, Doggett NA, Taschner PE, Gardiner RM, Mole SE. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 316-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668354

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Batten Disease

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Polyunsaturated fatty acids reverse the lysosomal storage and accumulation of subunit 9 of mitochondrial F1F0-ATP synthase in cultured lymphoblasts from patients with Batten disease. Author(s): Bennett MJ, Boriack RL, Boustany RM. Source: Journal of Inherited Metabolic Disease. 1997 July; 20(3): 457-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9266381

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Presence of abnormal amounts of dolichols in the urinary sediment of Batten disease patients. Author(s): Kin NM, Wolfe LS. Source: Pediatric Research. 1982 July; 16(7): 530-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7110772

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Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis. Author(s): Cooper JD. Source: Current Opinion in Neurology. 2003 April; 16(2): 121-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644737

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Rapid detection of the major deletion in the Batten disease gene CLN3 by allele specific PCR. Author(s): Taschner PE, de Vos N, Breuning MH. Source: Journal of Medical Genetics. 1997 November; 34(11): 955-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9391897

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Rapid diagnostic test for the major mutation underlying Batten disease. Author(s): Jarvela I, Mitchison HM, Munroe PB, O'Rawe AM, Mole SE, Syvanen AC. Source: Journal of Medical Genetics. 1996 December; 33(12): 1041-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9004140

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Refined localization of the Batten disease gene (CLN3) by haplotype and linkage disequilibrium mapping to D16S288-D16S383 and exclusion from this region of a variant form of Batten disease with granular osmiophilic deposits. Author(s): Mitchison HM, O'Rawe AM, Lerner TJ, Taschner PE, Schlumpf K, D'Arigo K, de Vos N, Gormally E, Phillips HA, Thompson AD, et al. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 312-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668353

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Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12. Author(s): Callen DF, Baker E, Lane S, Nancarrow J, Thompson A, Whitmore SA, MacLennan DH, Berger R, Cherif D, Jarvela I, et al. Source: American Journal of Human Genetics. 1991 December; 49(6): 1372-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746562

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Retinoyl complexes in Batten disease. Author(s): Nelson EC, Halley BA. Source: Science. 1977 November 4; 198(4316): 527-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=910148

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Role of subunit-9 of mitochondrial ATP synthase in Batten disease. Author(s): Johnson DW, Speier S, Qian WH, Lane S, Cook A, Suzuki K, Daniel P, Boustany RM. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 350-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668362

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Round-table discussion of animal models of ceroid-lipofuscinosis (Batten disease). Author(s): Jolly RD. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 278-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411980

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Seizures, depression and dementia in teenagers with Batten disease. Author(s): Boustany RM, Filipek P. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 252-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411973

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Sheep and other animals with ceroid-lipofuscinoses: their relevance to Batten disease. Author(s): Jolly RD, Martinus RD, Palmer DN. Source: American Journal of Medical Genetics. 1992 February 15; 42(4): 609-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1535180

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Specific delay of degradation of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid lipofuscinosis (Batten disease). Author(s): Ezaki J, Wolfe LS, Higuti T, Ishidoh K, Kominami E. Source: Journal of Neurochemistry. 1995 February; 64(2): 733-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7830067

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Spectrum of mutations in the Batten disease gene, CLN3. Author(s): Munroe PB, Mitchison HM, O'Rawe AM, Anderson JW, Boustany RM, Lerner TJ, Taschner PE, de Vos N, Breuning MH, Gardiner RM, Mole SE. Source: American Journal of Human Genetics. 1997 August; 61(2): 310-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9311735

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Spielmeyer-Vogt disease: clinical and neurophysiological aspects. Author(s): Piattella L, Cardinali C, Zamponi N, Papa O. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1991 August; 7(4): 226-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1657386

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Storage bodies in the ceroid-lipofuscinoses (Batten disease): low-molecular-weight components, unusual amino acids and reconstitution of fluorescent bodies from nonfluorescent components. Author(s): Palmer DN, Bayliss SL, Clifton PA, Grant VJ. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 292-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411984

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Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease. Author(s): Hall NA, Thomas-Oates JE, Dell A, Haltia M, Lake BD, Patrick AD. Source: American Journal of Medical Genetics. 1992 February 15; 42(4): 580-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1609839

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Studies in batten disease. I. Peroxidase deficiency in granulocytes. Author(s): Armstrong D, Dimmitt S, VanWormer DE. Source: Archives of Neurology. 1974 February; 30(2): 144-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4810892

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The 8th International Congress on Neuronal Ceroid Lipofuscinoses (Batten disease)-NCL 2000, 20-24 September, 2000, Oxford, United Kingdom. Author(s): Goebel HH. Source: Brain Pathology (Zurich, Switzerland). 2001 April; 11(2): 259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11303800

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The Batten disease gene product (CLN3p) is a Golgi integral membrane protein. Author(s): Kremmidiotis G, Lensink IL, Bilton RL, Woollatt E, Chataway TK, Sutherland GR, Callen DF. Source: Human Molecular Genetics. 1999 March; 8(3): 523-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9949212

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The differential diagnosis of the various forms of Batten disease by rectal biopsy. Author(s): Lake BD. Source: Birth Defects Orig Artic Ser. 1976; 12(3): 455-62. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=953200

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The neuronal ceroid lipofuscinoses (Batten disease): a group of lysosomal proteinoses. Author(s): Palmer DN, Hay JM. Source: Advances in Experimental Medicine and Biology. 1996; 389: 129-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8861002

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The neuronal ceroid-lipofuscinoses (Batten disease): a new class of lysosomal storage diseases. Author(s): Bennett MJ, Hofmann SL. Source: Journal of Inherited Metabolic Disease. 1999 June; 22(4): 535-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407785

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The neuronal ceroid-lipofuscinoses (Batten disease): comparative aspects. Author(s): Jolly RD, Palmer DN. Source: Neuropathology and Applied Neurobiology. 1995 February; 21(1): 50-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7770121

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The ovine model of neuronal ceroid lipofuscinosis (NCL): its contribution to understanding the pathogenesis of Batten disease. Author(s): Jolly RD. Source: Neuropediatrics. 1997 February; 28(1): 60-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151325

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The subcellular location of the yeast Saccharomyces cerevisiae homologue of the protein defective in the juvenile form of Batten disease. Author(s): Croopnick JB, Choi HC, Mueller DM. Source: Biochemical and Biophysical Research Communications. 1998 September 18; 250(2): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753630

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The yeast model for Batten disease: a role for Btn2p in the trafficking of the Golgiassociated vesicular targeting protein, Yif1p. Author(s): Chattopadhyay S, Roberts PM, Pearce DA. Source: Biochemical and Biophysical Research Communications. 2003 March 14; 302(3): 534-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615067

•

The yeast model for batten disease: mutations in BTN1, BTN2, and HSP30 alter pH homeostasis. Author(s): Chattopadhyay S, Muzaffar NE, Sherman F, Pearce DA. Source: Journal of Bacteriology. 2000 November; 182(22): 6418-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11053386

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•

Thirty years of Batten disease research: present status and future goals. Author(s): Rider JA, Rider DL. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 231-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191106

•

Tissue and cellular distribution of subunit c of ATP synthase in Batten disease (neuronal ceroid-lipofuscinosis). Author(s): Rowan SA, Lake BD. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 172-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668325

•

Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells. Author(s): Elleder M, Drahota Z, Lisa V, Mares V, Mandys V, Muller J, Palmer DN. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 213-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668332

•

Tissue expression and subcellular localization of CLN3, the Batten disease protein. Author(s): Margraf LR, Boriack RL, Routheut AA, Cuppen I, Alhilali L, Bennett CJ, Bennett MJ. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191116

•

Translocation 10;18 in a patient with juvenile neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Tuck-Muller CM, Dyken PR, Li S, Chen H, Labbe E, Wertelecki W. Source: American Journal of Medical Genetics. 1995 June 5; 57(2): 168-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7668324

•

Turnover of F1F0-ATP synthase subunit 9 and other proteolipids in normal and Batten disease fibroblasts. Author(s): Tanner A, Shen BH, Dice JF. Source: Biochimica Et Biophysica Acta. 1997 October 24; 1361(3): 251-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9375799

•

Upregulation of Bcl-2 and elevation of ceramide in Batten disease. Author(s): Puranam K, Qian WH, Nikbakht K, Venable M, Obeid L, Hannun Y, Boustany RM. Source: Neuropediatrics. 1997 February; 28(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151319

Studies

31

•

Urinary sediment dolichol excretion in patients with Batten disease and other neurodegenerative and storage disorders. Author(s): Bennett MJ, Mathers NJ, Hemming FW, Zweije-Hofman I, Hosking GP. Source: Pediatric Research. 1985 February; 19(2): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3920636

•

YAC and cosmid contigs spanning the Batten disease (CLN3) region at 16p12.1-p11.2. Author(s): Jarvela IE, Mitchison HM, O'Rawe AM, Munroe PB, Taschner PE, de Vos N, Lerner TJ, D'Arigo KL, Callen DF, Thompson AD, et al. Source: Genomics. 1995 September 20; 29(2): 478-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8666398

33

CHAPTER 2. ALTERNATIVE MEDICINE AND BATTEN DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to batten disease. 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 batten disease 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 “batten disease” (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 batten disease: •

Assessment of dietary therapies in a canine model of Batten disease. Author(s): Siakotos AN, Hutchins GD, Farlow MR, Katz ML. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5 Suppl A: 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588988

•

Assessment of plasma carnitine concentrations in relation to ceroid lipofuscinosis in Tibetan Terriers. Author(s): Katz ML, Sanders DA, Sanders DN, Hansen EA, Johnson GS. Source: Am J Vet Res. 2002 June; 63(6): 890-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061538

34

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•

Change in content, incorporation and lipoxygenation of docosahexaenoic acid in retina and retinal pigment epithelium in canine ceroid lipofuscinosis. Author(s): Reddy TS, Birkle DL, Armstrong D, Bazan NG. Source: Neuroscience Letters. 1985 August 16; 59(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2931631

•

CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and mediated by ceramide. Author(s): Puranam KL, Guo WX, Qian WH, Nikbakht K, Boustany RM. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 294-308. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191118

•

Dietary carnitine supplements slow disease progression in a putative mouse model for hereditary ceroid-lipofuscinosis. Author(s): Katz ML, Rice LM, Gao CL. Source: Journal of Neuroscience Research. 1997 October 1; 50(1): 123-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9379488

•

In-utero and post-delivery supplementation of motor neuron degeneration mutant mice with polyunsaturated fatty acids does not alter the clinical or pathological course. Author(s): Bennett MJ, Boriack RL, Birch DG. Source: Neuropediatrics. 1997 February; 28(1): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151333

•

Juvenile neuronal ceroid-lipofuscinosis: developmental progress after supplementation with polyunsaturated fatty acids. Author(s): Bennett MJ, Gayton AR, Rittey CD, Hosking GP. Source: Developmental Medicine and Child Neurology. 1994 July; 36(7): 630-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8034126

•

Low erythrocyte plasmalogen and plasma docosahexaenoic acid (DHA) in juvenile neuronal ceroid-lipofuscinosis (JNCL). Author(s): Kohlschutter A, Schade B, Blomer B, Hubner C. Source: Journal of Inherited Metabolic Disease. 1993; 16(2): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8411986

•

Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis. Author(s): Persaud-Sawin DA, VanDongen A, Boustany RM. Source: Human Molecular Genetics. 2002 September 1; 11(18): 2129-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189165

Alternative Medicine 35

•

Retinal degeneration in retinitis pigmentosa and neuronal ceroid lipofuscinosis: An overview. Author(s): Birch DG. Source: Molecular Genetics and Metabolism. 1999 April; 66(4): 356-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10191129

•

Role of palmitoyl-protein thioesterase in cell death: implications for infantile neuronal ceroid lipofuscinosis. Author(s): Cho S, Dawson PE, Dawson G. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2001; 5 Suppl A: 53-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589008

•

Secondary carnitine deficiency and impaired docosahexaenoic (22:6n-3) acid synthesis: a common denominator in the pathophysiology of diseases of oxidative phosphorylation and beta-oxidation. Author(s): Infante JP, Huszagh VA. Source: Febs Letters. 2000 February 18; 468(1): 1-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10683429

•

Therapeutic modification of membrane lipid abnormalities in juvenile neuronal ceroid-lipofuscinosis (Batten disease). Author(s): Bennett MJ, Hosking GP, Gayton R, Thompson G, Galloway JH, Cartwright IJ. Source: Am J Med Genet Suppl. 1988; 5: 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146326

•

Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics. Author(s): Griffin JL, Muller D, Woograsingh R, Jowatt V, Hindmarsh A, Nicholson JK, Martin JE. Source: Physiological Genomics. 2002 December 3; 11(3): 195-203. Epub 2002 October 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12388797

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/

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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.

37

CHAPTER 3. PERIODICALS AND NEWS ON BATTEN DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover batten disease.

News Services and Press Releases One of the simplest ways of tracking press releases on batten disease is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “batten disease” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to batten disease. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “batten disease” (or synonyms). The following was recently listed in this archive for batten disease: •

Gene For Batten Disease Identified Source: Reuters Medical News Date: September 22, 1995

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Batten Disease

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “batten disease” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “batten disease” (or synonyms). If you know the name of a company that is relevant to batten disease, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “batten disease” (or synonyms).

Academic Periodicals covering Batten Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to batten disease. In addition to

Periodicals and News

39

these sources, you can search for articles covering batten disease that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

41

APPENDICES

43

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 Institute7: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

7

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

44

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Physician Resources

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 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:9 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

8

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). 9 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 Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “batten disease” (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 1060 8 93 0 16 1177

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “batten disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

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

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.

Physician Resources

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Coffee Break: Tutorials for Biologists15 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.16 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.17 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/.

15 Adapted 16

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. 17 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on batten disease can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to batten disease. 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 batten disease. 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 “batten disease”:

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Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Gaucher's Disease http://www.nlm.nih.gov/medlineplus/gauchersdisease.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Head and Brain Malformations http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Polio and Post-Polio Syndrome http://www.nlm.nih.gov/medlineplus/polioandpostpoliosyndrome.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Batten Disease Facts and Fictions Summary: Also known as Spielmeyer-Vogt-Sjogren-Batten Disease, Batten Disease is the most common form of a group of disorders called neuronal ceroid lipofuscinoses (or NCLs). Source: Batten's Disease Support and Research Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7985

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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 batten disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Batten Disease The following is a list of associations that provide information on and resources relating to batten disease: •

Batten Disease Support and Research Association Telephone: (740) 927-4298 Toll-free: (800) 448-4570 Fax: (614) 445-4191 Email: [email protected] Web Site: http://bdsra.org Background: The Batten Disease Support and Research Association (BDSRA) is a voluntary not-for-profit organization dedicated to promoting the civil and human rights of people with Batten disease. Batten disease, an extremely rare inherited disorder, is a progressive degenerative neurometabolic disease characterized by gradual intellectual deterioration, seizure episodes, progressive movement (motor) impairment, and progressive visual impairment. Symptoms begin to occur at approximately five to 13 years of age. The Association seeks to maximize the opportunities of affected individuals through medical, educational, vocational, rehabilitative, and financial means and to educate lay persons and professionals concerning the special needs of people with the disease. Established in 1987, the Batten Disease Support and Research

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Association provides referral services to help affected families secure benefits available by law and maintains a database of individuals with Batten disease on state, national, and international levels. It functions as a national registry for researchers throughout the world who are studying Batten disease. •

National Batten Disease Registry Telephone: (718) 494-5201 Toll-free: (800) 952-9628 Fax: (718) 982-6346 Email: [email protected] Background: The National Batten Disease Registry was established in 1987 to identify families affected with Batten disease and provide physicians and researchers with a computerized central data bank of vital information. Batten Disease is the juvenile form of a group of progressive, inherited neurological diseases known as neuronal ceroid lipofuscinoses (NCL). It occurs mostly in families of Northern European Scandinavian ancestry, and is marked by rapidly progressive vision failure and neurological disturbances, which may include deterioration of intellect. Since its inception, the Registry has expanded to provide additional services for both physicians and families. The information collected by the Registry is available to all researchers working on Batten disease. The Registry works closely with the Batten Disease Support and Research Association (BDSRA), gathering and disseminating information on Batten Disease. It provides parents with the latest medical developments, names of nearby physicians, and access to a second opinion. The Registry also puts parents in contact with other families. Relevant area(s) of interest: Batten Disease

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to batten disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with batten disease. 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 batten disease. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines.

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The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “batten disease” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “batten disease”. 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 “batten disease” (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 “batten disease” (or a synonym) into the search box, and click “Submit Query.”

55

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.18

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

18

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)19: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

19

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

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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

61

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

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

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

63

BATTEN DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [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] Amyloid beta-Protein: A 4 kD protein, 39-43 amino acids long, expressed by a gene located on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid

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filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (Down syndrome). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. [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] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angiography: Radiography of blood vessels after injection of a contrast medium. [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] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH]

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Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] 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] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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

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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] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [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] 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] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carcinogenic: Producing carcinoma. [EU] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain

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functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] 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] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [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] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH]

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CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] 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 engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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

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are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans)

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end of the body. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Diagnostic procedure: A method used to identify a disease. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [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

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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] Dolichol: Eicosamethyl octacontanonadecasen-1-o1. Polyprenol found in animal tissues that contains about 20 isoprene residues, the one carrying the alcohol group being saturated. [NIH]

Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] 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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] 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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH]

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Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fossa: A cavity, depression, or pit. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gastric: Having to do with the stomach. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus,

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transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophosphates: Any salt or ester of glycerophosphoric acid. [NIH] Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [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 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] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Haptoglobins: Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations

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within the hemoglobin molecule. [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] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormones: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various endocrine glands and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. [NIH] Human Rights: The rights of the individual to cultural, social, economic, and educational opportunities as provided by society, e.g., right to work, right to education, and right to social security. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Idiocy: Is the most severe degree of mental defect. [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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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]

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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] 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] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [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] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH]

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Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH]

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Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [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] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized

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by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [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] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological

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oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreatic: Having to do with the pancreas. [NIH] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [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]

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Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolipids: Protein-lipid combinations abundant in brain tissue, but also present in a wide variety of animal and plant tissues. In contrast to lipoproteins, they are insoluble in water,

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but soluble in a chloroform-methanol mixture. The protein moiety has a high content of hydrophobic amino acids. The associated lipids consist of a mixture of glycerophosphates, cerebrosides, and sulfoglycosphingolipids, while lipoproteins contain phospholipids, cholesterol, and triglycerides. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Psychic: Pertaining to the psyche or to the mind; mental. [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]

Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [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] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH]

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Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Rod: A reception for vision, located in the retina. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] 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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and

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types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [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] Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sulfoglycosphingolipids: Glycosphingolipids with a sulfate group esterified to one of the sugar groups. [NIH] Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream,

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reaching and affecting cells all over the body. [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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]

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Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] 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]

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] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

87

INDEX A Adaptability, 63, 66, 67 Adverse Effect, 63, 82 Affinity, 6, 63, 65 Algorithms, 63, 66 Alleles, 63, 75 Alternative medicine, 38, 63 Amino Acid Sequence, 63, 64, 72 Amino Acids, 5, 28, 63, 79, 80, 81 Amplification, 22, 63 Amyloid, 21, 63, 73 Amyloid beta-Protein, 21, 63 Anaesthesia, 64, 75 Anaphylatoxins, 64, 68 Anatomical, 64, 67, 74, 77 Angiography, 17, 64 Animal model, 10, 27, 30, 64 Antibodies, 11, 15, 21, 64, 65, 73, 77, 80 Antibody, 11, 63, 64, 68, 70, 73, 74, 77, 82 Anticoagulant, 64, 80 Antigen, 63, 64, 68, 74, 77 Antigen-Antibody Complex, 64, 68 Anus, 64, 68, 81 Apoptosis, 5, 7, 34, 64, 66 Aqueous, 65, 70, 76 Arginine, 13, 64, 65, 74 Arterial, 65, 80 Astrocytes, 4, 65, 77 Atrophy, 65, 78 Autoantibodies, 12, 65 Autoantigens, 65 B Base, 65, 75, 84 Basement Membrane, 65, 72 Basophils, 65, 73 Beta-pleated, 63, 65 Bilateral, 65, 82 Bile, 65, 76, 83 Bile Acids, 65, 83 Biochemical, 4, 5, 7, 9, 10, 15, 16, 19, 23, 29, 63, 65 Biological therapy, 65, 73 Biopsy, 28, 65 Biotechnology, 12, 38, 45, 65 Blood vessel, 64, 66, 67, 82, 84 Bone Marrow, 17, 66, 72 Brain Stem, 66, 67

C Calcium, 66, 68 Carbohydrates, 66, 78 Carcinogenic, 66, 80 Carnitine, 8, 18, 33, 34, 35, 66 Carotene, 66, 81 Caspase, 5, 66 Catabolism, 25, 66 Cell Cycle, 66, 85 Cell Death, 9, 35, 64, 66, 77 Cell Division, 66, 73, 76, 77, 79, 80 Cell membrane, 4, 66, 72, 79 Cell Survival, 11, 66, 73 Cell Transplantation, 10, 67 Central Nervous System, 4, 10, 67, 72, 73, 77, 78 Ceramide, 5, 30, 34, 67 Cerebellum, 20, 67 Character, 67, 70 Chemotactic Factors, 67, 68 Chemotherapeutic agent, 5, 67 Chin, 67, 76 Chloroform, 67, 81 Chloroquine, 25, 67 Cholesterol, 65, 67, 76, 81 Chondroitin sulfate, 4, 67 Chorioretinitis, 67, 82 Choroid, 67, 81, 82 Chromatin, 5, 64, 67, 71, 78 Chromosomal, 22, 63, 67, 74 Chromosome, 6, 15, 18, 20, 22, 26, 63, 67, 69, 73, 75, 84 Chronic, 67, 70, 83 CIS, 68, 81 Clinical trial, 3, 45, 68, 81 Cloning, 6, 8, 66, 68 Coculture, 17, 68 Cofactor, 68, 80, 84 Collagen, 65, 68, 72 Colon, 5, 68, 75 Complement, 12, 64, 68, 69, 72, 76 Complementary and alternative medicine, 33, 36, 68 Complementary medicine, 33, 69 Computational Biology, 45, 69 Cones, 69, 81 Conjugation, 69, 83 Connective Tissue, 66, 68, 69, 72, 83

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Connexins, 69, 72 Consciousness, 69, 70, 71 Constitutional, 69, 82 Contraindications, ii, 69 Contrast medium, 64, 69 Coordination, 67, 69 Cortical, 7, 69, 71, 82 Cranial, 67, 69, 78, 79 Cultured cells, 7, 70 Curative, 70, 84 Cysteine, 9, 70 Cystine, 70 Cytochrome, 70, 79 Cytokines, 12, 70, 77 Cytoplasm, 64, 65, 66, 70, 71, 73, 78, 83 D Degenerative, 10, 50, 51, 70 Deletion, 18, 26, 64, 70 Dementia, 27, 70 Dendrites, 70, 78 Deprivation, 5, 70 Diagnostic procedure, 38, 70 Direct, iii, 10, 70, 81, 83 Disease Progression, 8, 10, 34, 70 Dissociation, 63, 70 Dolichol, 14, 31, 71 Drug Interactions, 71 Dyes, 63, 65, 71, 78 E Effector, 68, 71 Efficacy, 7, 10, 71 Electrons, 65, 71, 79 Embryo, 71, 75, 80 Endotoxic, 71, 75 Endotoxins, 68, 71 Environmental Health, 44, 46, 71 Enzymatic, 66, 68, 71, 76, 81 Enzyme, 7, 9, 10, 11, 16, 66, 71, 72, 81, 83, 84, 85 Eosinophils, 71, 73 Epithelium, 65, 71 Erythrocytes, 66, 71 Excitatory, 71, 73 Excitotoxicity, 7, 71 Exocytosis, 72, 83 Exogenous, 72, 83 Exon, 18, 22, 72 Extracellular, 4, 63, 65, 69, 72 Extracellular Matrix, 4, 69, 72 Extracellular Space, 72 F Family Planning, 45, 72

Fat, 66, 67, 72, 75, 80, 82 Fatty acids, 9, 18, 72, 73 Fetus, 72, 80 Fibroblasts, 14, 15, 23, 30, 72 Fossa, 67, 72 G Ganglia, 72, 77, 79 Gap Junctions, 4, 69, 72 Gastric, 66, 72 Gene, 4, 5, 6, 7, 8, 10, 13, 14, 15, 18, 19, 20, 22, 24, 25, 26, 27, 28, 37, 63, 66, 69, 72, 73 Gene Expression, 5, 19, 20, 72 Gene Therapy, 10, 72 Genetic Engineering, 66, 68, 72 Genotype, 73, 79 Glutamate, 11, 71, 73 Glutamic Acid, 11, 14, 73, 78 Glycerol, 73, 79 Glycerophosphates, 73, 81 Glycerophospholipids, 73, 79 Glycoproteins, 73, 75, 80 Glycosaminoglycan, 67, 73 Glycosidic, 73, 78 Governing Board, 73, 80 Granulocytes, 28, 73, 75, 85 Growth factors, 7, 73, 77 H Haplotypes, 15, 20, 73 Haptens, 63, 73 Haptoglobins, 14, 73 Hemoglobin, 71, 73, 74 Hemoglobinopathies, 72, 73 Hereditary, 7, 10, 34, 74, 77, 82 Heredity, 72, 74 Heterogeneity, 63, 74 Histones, 67, 74 Homeostasis, 29, 74 Homologous, 9, 63, 69, 72, 74, 83 Hormones, 70, 74 Human Rights, 51, 74 Hybrid, 6, 74 Hydrogen, 65, 66, 74, 77, 79 Hydrophobic, 11, 19, 73, 74, 81 I Idiocy, 17, 74 Immune response, 11, 64, 65, 73, 74, 76, 85 Immune system, 12, 65, 74, 85 Immunogenic, 74, 75 Immunology, 63, 74 Impairment, 5, 51, 74, 76 In situ, 7, 74 In vitro, 7, 9, 10, 11, 72, 74, 84

89

In vivo, 72, 74 Induction, 11, 75 Infancy, 75 Infantile, 3, 5, 8, 9, 10, 13, 14, 17, 21, 22, 23, 24, 27, 35, 75 Insight, 9, 25, 75 Intracellular, 4, 7, 9, 11, 17, 18, 22, 75, 76 Intrinsic, 63, 65, 75 Invasive, 75, 76 Ion Channels, 65, 75 Isoelectric, 8, 75 K Kb, 18, 44, 75 L Labile, 68, 75 Large Intestine, 75, 81 Lesion, 75, 76 Leucocyte, 75, 76 Leukemia, 72, 75 Linkage, 6, 14, 15, 22, 26, 75 Linkage Disequilibrium, 15, 26, 75 Lipid, 8, 9, 35, 67, 73, 75, 76, 80 Lipid A, 35, 75 Lipofuscin, 17, 21, 67, 75 Lipopolysaccharides, 75, 76 Liposome, 19, 76 Liver, 65, 66, 67, 76 Localization, 5, 16, 21, 23, 26, 30, 76 Lymphoblasts, 24, 26, 76 Lymphoid, 64, 75, 76 Lysine, 18, 74, 76 Lysosome, 4, 7, 9, 10, 11, 76 M Magnetic Resonance Imaging, 18, 76 Major Histocompatibility Complex, 73, 76 MEDLINE, 45, 76 Meiosis, 76, 83 Membrane, 5, 6, 7, 9, 22, 24, 28, 35, 65, 66, 67, 68, 72, 75, 76, 79, 81, 83, 85 Membrane Lipids, 76, 79 Memory, 70, 76 Meninges, 67, 76 Mental, iv, 3, 4, 5, 9, 10, 44, 46, 67, 70, 74, 76, 81 Mental Retardation, 4, 9, 76 Methanol, 76, 81 Microglia, 65, 77 Microscopy, 4, 11, 65, 77 Mitosis, 64, 77 Mitotic, 5, 77 Modification, 35, 72, 77

Molecular, 4, 5, 6, 8, 9, 12, 13, 14, 15, 16, 17, 18, 20, 22, 24, 25, 28, 30, 34, 35, 45, 47, 65, 69, 77 Molecule, 64, 65, 67, 68, 70, 71, 73, 74, 77, 79, 81, 83, 84 Monitor, 77, 78 Monoclonal, 21, 77 Monoclonal antibodies, 21, 77 Morphology, 5, 77 Mutagenesis, 9, 77 Mutagens, 77 N Necrosis, 64, 77, 82 Nervous System, 4, 9, 28, 64, 67, 77, 78, 79, 85 Neural, 4, 8, 9, 11, 63, 64, 77 Neurodegenerative Diseases, 7, 10, 77 Neurologic, 8, 78 Neurons, 4, 5, 10, 11, 70, 71, 72, 78, 83 Neuroretinitis, 78, 82 Neurotoxic, 8, 78 Neurotoxicity, 9, 78 Neurotransmitter, 73, 75, 78 Neutrophils, 73, 78 Night Blindness, 78, 82 Nuclear, 5, 69, 71, 77, 78 Nuclei, 69, 71, 72, 73, 74, 76, 77, 78 Nucleus, 64, 65, 67, 70, 71, 76, 78, 80 O Ocular, 16, 21, 78 Oligosaccharides, 14, 28, 78 Opsin, 78, 81, 82 Optic Nerve, 78, 81, 82 Organ Culture, 78, 84 Oxidation, 35, 70, 78 Oxidative Phosphorylation, 35, 79 P Palliative, 79, 84 Pancreatic, 66, 79 Particle, 76, 79 Pathologic, 64, 65, 79 Pathologic Processes, 64, 79 Pathophysiology, 6, 35, 79 Peptide, 79, 80, 81 Peripheral Nervous System, 78, 79 Pharmacologic, 79, 84 Phenotype, 11, 79 Phospholipids, 18, 72, 76, 79, 81 Phosphorus, 66, 79 Phosphorylated, 14, 79 Phosphorylation, 19, 79 Photoreceptor, 5, 79, 82

90

Batten Disease

Pigment, 21, 67, 75, 79, 81 Plants, 77, 79, 80, 84, 85 Plaque, 63, 80 Plasma, 7, 8, 18, 22, 33, 34, 64, 66, 73, 80 Plasma cells, 64, 80 Pneumonia, 69, 80 Polymorphic, 6, 80 Polysaccharide, 64, 73, 80 Polyunsaturated fat, 26, 34, 80 Posterior, 67, 80 Postnatal, 80, 83 Postsynaptic, 80 Practice Guidelines, 46, 80 Prenatal, 24, 71, 80 Prenatal Diagnosis, 24, 80 Presynaptic, 78, 80, 83 Progression, 10, 64, 80 Progressive, 5, 7, 10, 51, 52, 70, 77, 78, 80, 82 Promoter, 11, 80 Prophase, 80, 83 Protein C, 6, 12, 63, 80 Protein S, 7, 8, 19, 25, 63, 66, 80 Proteins, 6, 8, 9, 12, 19, 63, 64, 66, 67, 68, 69, 70, 72, 74, 75, 76, 77, 79, 80, 81, 82, 83, 84, 85 Proteoglycans, 4, 65, 80 Proteolipids, 30, 80 Proteolytic, 68, 81 Psychic, 76, 81, 82 Public Policy, 45, 81 Publishing, 12, 81 R Radioactive, 74, 77, 78, 81 Randomized, 71, 81 Receptor, 64, 79, 81 Recombinant, 10, 81, 84 Recombination, 69, 72, 81 Rectal, 28, 81 Rectum, 64, 68, 75, 81 Refer, 1, 68, 76, 81 Regimen, 71, 81 Rehabilitative, 51, 81 Retina, 10, 21, 34, 67, 69, 78, 81, 82, 85 Retinal, 7, 8, 10, 11, 34, 35, 78, 81, 82 Retinal pigment epithelium, 34, 81 Retinitis, 35, 82 Retinitis Pigmentosa, 35, 82 Retinol, 81, 82 Retroviral vector, 72, 82 Rheumatoid, 67, 82 Rhodopsin, 78, 81, 82

Rod, 79, 82 S Screening, 24, 68, 82 Secretory, 82 Sediment, 19, 26, 31, 82 Seizures, 5, 7, 8, 10, 27, 82 Sequencing, 4, 82 Sequester, 82, 83 Serum, 5, 64, 68, 82 Side effect, 63, 65, 82, 84 Skull, 82, 84 Social Security, 74, 82 Soft tissue, 66, 82 Soybean Oil, 80, 82 Specialist, 52, 82 Species, 67, 74, 76, 77, 82, 84, 85 Specificity, 9, 63, 82 Sperm, 67, 83 Spinal cord, 65, 66, 67, 76, 77, 79, 83 Sporadic, 77, 83 Stem Cells, 11, 83 Stool, 68, 75, 83 Subclinical, 82, 83 Substrate, 8, 9, 83 Substrate Specificity, 9, 83 Sulfoglycosphingolipids, 81, 83 Sulfotransferases, 25, 83 Supplementation, 34, 83 Symptomatic, 6, 83 Synapse, 80, 83, 84 Synapsis, 83 Synaptic, 18, 78, 83 Synaptic Vesicles, 18, 83 Systemic, 67, 83 Systemic lupus erythematosus, 67, 83 Systemic therapy, 67, 83 T Temporal, 9, 84 Therapeutics, 84 Thrombin, 80, 84 Thrombomodulin, 80, 84 Thrombosis, 80, 84 Tissue, 4, 30, 64, 65, 66, 67, 69, 70, 72, 75, 76, 78, 79, 80, 81, 82, 83, 84 Tissue Culture, 4, 84 Toxic, iv, 69, 76, 84 Toxicity, 71, 84 Toxicology, 46, 84 Toxins, 64, 71, 77, 84 Transfection, 66, 72, 84 Transmitter, 65, 75, 83, 84 Transplantation, 11, 17, 76, 84

91

Trisomy, 64, 84 U Urinary, 19, 26, 31, 84 Urine, 84 V Vaccines, 84, 85 Vascular, 63, 67, 84 Vector, 10, 84 Vegetative, 7, 85 Vein, 78, 85 Venous, 80, 85 Vesicular, 29, 85 Veterinary Medicine, 45, 85 Viral, 10, 85 Viral vector, 10, 85

Virus, 5, 72, 80, 82, 85 Visual field, 82, 85 Vitreous, 67, 81, 85 Vitreous Body, 67, 81, 85 Vitro, 85 W White blood cell, 64, 76, 80, 85 X Xenograft, 64, 85 X-ray, 8, 69, 78, 85 Y Yeasts, 79, 85 Z Zymogen, 80, 85

92

Batten Disease