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

LEUKODYSTROPHY 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

ii

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., 1960Leukodystrophy: 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: 0-497-00654-5 1. Leukodystrophy-Popular works. I. Title.

iii

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.

iv

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 leukodystrophy. 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.

v

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.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LEUKODYSTROPHY ................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Leukodystrophy............................................................................. 3 E-Journals: PubMed Central ....................................................................................................... 19 The National Library of Medicine: PubMed ................................................................................ 19 CHAPTER 2. NUTRITION AND LEUKODYSTROPHY.......................................................................... 65 Overview...................................................................................................................................... 65 Finding Nutrition Studies on Leukodystrophy............................................................................ 65 Federal Resources on Nutrition ................................................................................................... 66 Additional Web Resources ........................................................................................................... 67 CHAPTER 3. ALTERNATIVE MEDICINE AND LEUKODYSTROPHY ................................................... 69 Overview...................................................................................................................................... 69 National Center for Complementary and Alternative Medicine.................................................. 69 Additional Web Resources ........................................................................................................... 70 General References ....................................................................................................................... 71 CHAPTER 4. PATENTS ON LEUKODYSTROPHY ................................................................................ 73 Overview...................................................................................................................................... 73 Patents on Leukodystrophy.......................................................................................................... 73 Patent Applications on Leukodystrophy ...................................................................................... 75 Keeping Current .......................................................................................................................... 77 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 81 Overview...................................................................................................................................... 81 NIH Guidelines............................................................................................................................ 81 NIH Databases............................................................................................................................. 83 Other Commercial Databases....................................................................................................... 85 APPENDIX B. PATIENT RESOURCES ................................................................................................. 87 Overview...................................................................................................................................... 87 Patient Guideline Sources............................................................................................................ 87 Associations and Leukodystrophy................................................................................................ 89 Finding Associations.................................................................................................................... 90 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 93 Overview...................................................................................................................................... 93 Preparation................................................................................................................................... 93 Finding a Local Medical Library.................................................................................................. 93 Medical Libraries in the U.S. and Canada ................................................................................... 93 ONLINE GLOSSARIES.................................................................................................................. 99 Online Dictionary Directories ..................................................................................................... 99 LEUKODYSTROPHY DICTIONARY ....................................................................................... 101 INDEX .............................................................................................................................................. 141

1

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 leukodystrophy 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 leukodystrophy, 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 leukodystrophy, 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 leukodystrophy. 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 leukodystrophy, 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 leukodystrophy. The Editors

1

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

3

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

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

Project Title: ALEXANDER MECHANISMS

DISEASE:

CELLULAR

AND

MOLECULAR

Principal Investigator & Institution: Messing, Albee; Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 28-FEB-2007

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).

4

Leukodystrophy

Summary: Alexander disease is a rare, fatal degenerative disease, classified among the leukodystrophies because of the severe hypomyelination seen in young infants or the demyelination seen in older children. The pathological signature of the disorder is the Rosenthal fiber, an accumulation of intermediate filaments and small heat shock proteins in astrocytes throughout the CNS. Sequencing the GFAP gene revealed single base changes in the coding region, predicting, non-conservative amino acid substitutions, in 12 of 13 patients examined to date. All mutations are heterozygous, suggesting a dominant, gain-of-function mechanism. Alexander disease therefore represents the first example of a primary genetic disorder of astrocytes, one of the major cell types in the vertebrate central nervous system. The goals of this Program Project are to investigate the means by which GFAP mutations lead to inclusion bodies, disruption of the astrocyte cytoskeleton, astrocyte, dysfunction, and severe consequences for oligodendrocytes in the central nervous system. We will continue genetic studies of Alexander disease patients with unusual clinical presentations to clarify the range of disorders associated with GFAP mutations; develop animal models carrying the same mutations as those identified in humans; and explore potential approaches for interfering with the effects of the mutant protein. Our studies span molecular, biochemical, cellular, and morphological approaches to these questions. The Program will link four laboratories; three of these already have a proven record of productive interactions, and a fourth group will bring unique expertise in studying filament assembly. The Program will promote an expanded effort on the role of glial filament dysfunction in disease, by fostering sharing of reagents, animals, and results between the four labs, cross-fertilization of ideas, and regular communication and meetings among laboratory members. These studies promise novel insights into the role of glial filaments in the cell biology of astrocytes, and the role of astrocytes in brain function and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANIMAL MODEL OF GLOBOID CELL LEUKODYSTROPHY IN RHESUS MONKEYS: LYSOSOMAL STORAGE Principal Investigator & Institution: Baskin, Gary B.; Head, Pathology Department; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002 Summary: Globoid cell leukodystrophy is a rare autosomal recessive genetic disease caused by low levels of B-galactosidase activity, a lysosomal enzyme important in myelin metabolism. An infant rhesus monkey with this disease was diagnosed at TRPRC in 1989. Since then, we intentionally inbred this group of animals and in 1996 observed two additional affected infants. These two homozygous affected animals allowed us, in collaboration with Dr. David Wenger, Jefferson Medical College, Philadelphia, to identify the disease-causing mutation in the rhesus GALC gene and to unequivocally identify 22 carrier animals by PCR. The sequence of the rhesus GALC cDNA is 98% identical to the human, and the deduced amino acid sequence is 97% identical to that of humans. The mutation responsible for GLD in these monkeys consists of the deletion of the AC dinucleotide corresponding to cDNA positions 387 and 388. This results in a frame shift, leading to a premature stop codon. GALC activity was measured in the 2 homozygous affected, 21 normal and 20 carrier monkeys. The 2 affected infants had a GALC activity less than 2% of normal. The average activity for 21 normal monkeys was 0.94 nmol/hr/mg of protein, while the average for 20 carriers was 0.53. Psychosine levels in the brains of affected infants were very high. We established fibroblast and EBV-transformed lymphocyte cultures from these homozygous infants,

Studies

5

and have initiated in vitro therapeutic studies with retroviral vectors containing the human GALC gene. We have performed chorionic villus sampling for 3 birth seasons and have accurately diagnosed the genetic status of the fetuses each year prior to birth. In a related subproject, we have begun preliminary studies to determine the most appropriate way to deliver therapeutic genes to affected monkeys. This nonhuman primate model will be valuable for studies of gene therapy of this and similar disorders. FUNDING Base Grant, Venture Research PUBLICATIONS Luzi P, Rafi MA, Victoria T, Baskin GB, Wenger DA. Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene, and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate. Genomics 42:319-324, 1997; Baskin GB, Ratterree M, Davison BB, Falkenstein KP, Clarke MR, England JD, Vanier MT, Luzi P, Rafi MA, Wenger DA. Genetic Galactocerebrosidase deficiency (globoid cell leukodystrophy, Krabbe disease) in rhesus monkeys. Lab Anim Sci 48:476Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS Principal Investigator & Institution: Merchant, Fatima; Lead Research Engineer; Advanced Digital Imaging Research, Llc 2450 S Shore Blvd, Ste 305 League City, Tx 775732997 Timing: Fiscal Year 2004; Project Start 01-APR-2000; Project End 19-MAR-2006 Summary: (provided by applicant): This project will further develop automated instrumentation and image analysis techniques to detect gene duplications or deletions in interphase FISH, which are difficult to detect by routine cytogenetics. There is a growing list of genetic disorders that result from chromosomal anomalies, related to either duplications or deletions. These include: (1) neuropathies; Charcot-Marie-Tooth Disease (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP), (2) neurological disorders; Pelizaeus-Merzbacher Disease (PMD) and X-Linked Spastic Paraplegia (SPG2), (3) muscular wasting disorders; Duchene (DMD) and Becker Muscular Dystrophy (BMD), (4) contiguous-gene syndromes; Smith-Magenis Syndrome (SMS). Our approach is to use readily available DNA probes, followed by automated genetic screening to detect duplications/deletions. We will develop an imaging system for the automated identification of interphase cells, and use sophisticated image analysis for high-resolution detection and separation of microscopic rearrangements. In the Phase I project we evaluated the feasibility of newly developed imaging algorithms, for effectively and precisely identifying the separation of FISH dot duplicates. Algorithms were developed for automatically (1) segmenting dots, (2) computing the integrated fluorescence intensity of dots, (3) determining the separation distance, and (4) classifying duplicates and single dots. In Phase II we will incorporate the newly developed imaging algorithms into our automated imaging system, and test the prototype clinically. We will also develop and implement three-dimensional modeling techniques to obtain an unbiased estimate of the spatial distance between duplicated genes. Phase III will commercialize the instrument. Computer automation will make genetic screening practical on a large scale by reducing costs and relieving humans of tedious duties. This approach will be most valuable to medical genetics, particularly for screening CMT1A/HNPP, PMD/SPG2, DMD/BMD, and SMS. Duplications have also been identified for the Prader-Willi /Angelman syndrome region that result in autism. Duplications, such as for 22ql 1.2 and 17pl 1.2 have been described and result in a rather mild phenotype. But duplications of the Williams syndrome region have not been described and thus, the phenotype is unknown. The ability to screen patients for

6

Leukodystrophy

duplications by interphase FISH analysis will likely identify a large number of individuals that would benefit from medical intervention. It may uncover syndromes that previously had no identifiable etiology. This will provide a screening test and eventually a diagnostic test for those individuals with perhaps mild phenotypes, such as learning disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL LEUKODYSTROPHY

BIOLOGICAL

ANALYSIS

OF

CACH/VWM

Principal Investigator & Institution: Proschel, Christoph; Biomedical Genetics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-APR-2006 Summary: (provided by applicant): Diseases of militated white matter tracts in the central nervous system (CNS) represent one of the most frequent neurological disorders. Those known to be inheritable are referred to as leukodystrophies. In many instances the identification of specific genetic lesions has helped explain the pathology observed in patients. This has not been the case for the recently identified mutations in the subunits of translation initiation factor 2B (eIF2B) in patients diagnosed with autosomal recessive Childhood Ataxia with Diffuse CNS Hypomyelination (CACH)/Vanishing White Matter Disease (VWM; MIM 603896). The lack of a suitable experimental system in which to directly test the effect of elF2B mutations on the biology of neural cell populations is a major obstacle in understanding the etiology of CACH/VWM disease. By applying our extensive experience in the isolation and culture of neural stem ceils and progenitors from both the rodent and human CNS, we established cultures of ceils with the characteristics of neural precursors from the brain of a CACH/VWM disease patient with known mutations in the epsilon subunit of elF2B (EIF2B5). This is the first example of an in vitro system using primary ceils directly isolated from a leukodystrophy patient. Analysis of these cultures using lineage specific markers revealed the presence of neurons, oligodendrocytes and astrocytes. In light of the clinical pathology, we initially focused on the oligodendrocyte compartment. Contrary to our expectations, oligodendrocytes derived from the patient's brain appeared normal by morphological criteria and progressive maturation of oligodendroglial lineage cells could be observed. However, only few glial fiballry acidic protein (GFAP) expressing cells were present and most of these ceils exhibited an atypical morphology. Also, the induction of GFAP + astrocytes using otherwise highly pro-astrocytic conditions was severely impaired. This suggests that a mutation in eIF2B5 leads to a defect in the formation of astrocytes in CACH/VWM disease. This does not preclude that oligodendrocytes may also be directly affected. However, the possibility that a deficiency in astrocyte function may contribute to the loss of white matter in CACH/VWM leukodystrophy in a non autonomous manner has important consequences for therapeutic strategies. The goal of the proposed research is to exploit this unique in vitro system to study the biological effects of eiF2B5 mutations on different CNS lineages in CACH/VWM disease patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR PATHOLOGY OF ALEXANDER DISEASE Principal Investigator & Institution: Goldman, James E.; Associate Professor; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006

Studies

7

Summary: We propose to examine several aspects of intermediate filament (IF) organization and cellular stress reactions that may be germane to an understanding of the pathophysiology of Alexander disease. Thus, the over-expression of IF proteins may lead to an abnormal organization of filaments, which subsequently leads to upregulating the transcription and translation of the small hsps, alphabeta-crystallin and hsp27. We must also consider that Alexander disease is a disorder in which a mutant gene expressed on one cell type (astrocyte) results in degeneration and/or abnormal development of another cell type (oligodendrocyte). We propose three specific aims: 1) How are mutant GFAPs expressed in cells and do they result in an abnormal organization of IFs? Is there an accumulation of IFs? Does the expression of mutant GFAPs alter IF turnover. 2. Does the accumulation of IFs lead to a cellular stress response, part of which leads to the up-regulation of small hsps? If so, what are the mechanism(s) that produce such a stress response? If IF accumulation induces small hsps, we will investigate intracellular stress signal pathways that may underlie this effect, focusing on HSF1 activation, MAP kinase activation (ERK1/2, JNK, p38 kinase), NF- kappaB activation, and protein kinase-N activation. 3. How does the expression of a mutant protein in one cell type in the CNS (astrocytes) produce deleterious effects on another cell type (oligodendrocytes)? Is the cellular stress response an important part of this link? Do the pathological changes in astrocytes interfere with oligodendrocyte differentiation and/or myelination? We will examine possible further consequences of IF aggregation, focusing on the possibility that "stressed" astrocytes regulate cytokines. These experiments will focus on how the accumulation of a protein in one cell type (Astrocytes) appears to produce deleterious effects on another cell type (oligodendrocytes), the rationale taken from experiments in which cytokines are toxic to oligodendrocytes. In addition, we will examine other potentially toxic substances, including reactive oxygen species. If the neuropathology of the transgenic mice that is constructing suggest a defect in oligodendrocyte development and/or myelination, then we will examine directly the interactions between astrocytes expressing GFAP mutations and oligodendrocyte progenitors using a cell culture system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: I/AUTOTAXIN

CNS

MYELINATION--ROLE

OF

PHOSPHODIESTERASE-

Principal Investigator & Institution: Fuss, Babette; Assistant Professor; Anatomy and Neurobiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-MAY-2004 Summary: (provided by applicant) The long-term goal of this project is to better understand the molecular mechanisms that determine central nervous system myelination during normal development as an approach to improve strategies for myelin repair under pathological, de-/dysmyelinating conditions, such as they occur in hereditary leukodystrophies. Since repair of the myelin sheath under such pathological conditions still remains limited, yet to be characterized molecular mechanisms are likely to significantly contribute to proper myelination. These mechanisms include those that are mediated by proteins derived from the myelin forming cells of the CNS, oligodendrocytes. The central hypothesis for the proposed studies is that soluble, oligodendrocyte-derived phosphodiesterase-I/autotaxin (PD-I alpha/ATX) is an essential component of a currently uncharacterized molecular process that regulates proper CNS myelination. PD-I alpha/ATX is released by differentiated oligodendrocytes at the developmental time-point at which oligodendrocytes are actively involved in the generation of the myelin sheath. The investigator's preliminary

8

Leukodystrophy

data indicate that the release of PD-I alpha/ATX is regulated by proteolytic cleavage. Accordingly, Specific Aim 1 will study the molecular mechanism that regulates the generation of soluble, oligodendrocyte-derived PD-I alpha/ATX. Since the primary sequence of PD-I-alpha/ATX reveals structural domains that are likely to be involved in cell-cell and/or cell-extracellular matrix interactions, potential PD-I alpha/ATXinteracting molecules of the CNS will be identified in the studies of Specific Aim 2 by using biochemical as well as molecular biological approaches. Taken together, these studies will provide novel insights into PD-I alpha/ATX-mediated events that control CNS myelination during development and that may stimulate remyelination in de/dysmyelinating diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DELIVERY OF THERAPEUTIC ENZYMES AND GENES TO THE CNS Principal Investigator & Institution: Reiser, Jakob; Associate Professor; Medicine; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Owing to the structural and functional complexity and relative inaccessibility of the central nervous system (CNS), most chronic neurologic and neurodegenerative disorders lack effective treatments, and, therefore, require the development of novel therapeutic approaches including gene therapy and cellular therapy. Krabbe disease, or globoid cell leukodystrophy (GLD), is an inherited, recessive disorder affecting the peripheral nervous system (PNS) and the CNS caused by defects of the lysosomal enzyme galactocerebrosidase (GALC). This enzyme catalyzes the lysosomal hydrolysis of galactosylceramide and galactosylsphingosine (psychosine). The enzyme defect causes a series of pathological changes including demyelination. This autosomal recessive disease affects humans and animals including dogs, mice, and rhesus monkeys. The goal of the proposed project is to explore gene therapy strategies for Krabbe disease using improved lentivirus-based gene and protein delivery strategies. These strategies will initially be tested in rats and later on extended to mice and rhesus monkeys affected with GLD. The Specific Aims are: 1. To modify HIV-l-based lentiviral vectors for improved transgene delivery and expression in the CNS. These vectors will harbor constitutive as well as regulatable promoters. Vectors will be pseudotyped with the vesicular stomatitis virus (VSV)-G glycoprotein. Pseudotypes involving the Mokola virus G glycoprotein will also be tested with a view toward distributing such vectors more globally in the CNS. Vector delivery will be carried out by direct brain injection. 2. To investigate protein transduction mechanisms with a view toward facilitating the global delivery in the CNS of GALC tagged with the transduction domain of HIV-1 TAT, the membrane translocating hydrophobic sequence from fibroblast growth factor or the herpes simplex virus VP22 protein. 3. To use lentiviral vectors to transfer the GALC cDNA into the brains of mice and rhesus monkeys affected with GLD to evaluate the capacity of such vectors to correct the GLD defect and histological abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DETERMINANTS OF DISEASE SEVERITY IN PMD Principal Investigator & Institution: Pankonin, Mark S.; Genetics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-2002

Studies

9

Summary: Axonal loss is an important cause of clinical deficits in patients with MS. Because the etiology of MS is not known, it is impossible to be certain of the precise sequence of events that leads to axonal injury in the disease. The study of another myelin related disorder Pelizaeus- Merzbacher disease (PMD), a disease with a known cause, i.e. mutations affecting the major CNS myelin protein proteolipid protein (PLP1) may provide a better understanding of alternative (to inflammation) disease mechanisms in PMD, which may also be important in MS. Magnetic resonance spectroscopy (MRS), and imaging (MRI), as well as various histological techniques will be utilized to identify the critical domains of this protein that mediate its axon maintaining function in an attempt to better understand the pathogenesis and temporal progression of PMD. Hopefully these findings will provide a model for the clinical deterioration found in PMD as well as MS, and perhaps lead to new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPERIMENTAL PATHOLOGY OF DEVELOPING NERVOUS SYSTEM Principal Investigator & Institution: Suzuki, Kinuko; Professor of Pathology and Laboratory Me; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-MAY-1986; Project End 31-JUL-2005 Summary: The ultimate goals of the investigations proposed in this application is to investigate the pathogenesis of the disease process and to explore therapeutic means of genetic neurodegenerative diseases, globoid cell leukodystrophy (GLD) and NiemannPick disease type C (NPC), using naturally occurring murine models, twitcher and NPC mice. GLD is a genetic demyelinating disease and formed myelin degenerates as result of apoptotic death of oligodendrocytes. NPC is a neurovisceral storage disease. Preliminary studies in our laboratory indicate apoptotic death of storage neurons and abnormal myelination suggesting problems in oligodendrocytes and/or oligodendrocyte progenitor cells. Chemokines/cytokines generated by cells within the CNS apparently play significant role(s) in pathogenesis of both diseases. In the murine model of GLD, twitcher mouse, massive infiltration of hematogenous lineage cells into the CNS is noted as a natural disease process. These cellular infiltrations appear to be regulated by pro-inflammatory cytokines and their inhibitors. In Aim 1, the mechanism of these cellular infiltration, role(s) of these hematogenous cells in the pathological process are investigated and also possible use of these cells as a vehicle to carry therapeutic gene in to the CNS will be explored. In Aim 2, oligodendrocyte progenitor cells will be investigated in twitcher CNS during demyelination as a natural disease process and during remyelination following bone marrow transplantation. The basic genetic defect of NPC is a defective intracellular transport of cholesterol. Cholesterol is an important lipid in normal neuronal maturation and myelination. Thus, in Aim 3, the underlying mechanism(s) of abnormal myelination and developmental pathological process will be investigated in NPC mouse. In NPC in humans as well as in mouse, neuronal storage is a very conspicuous pathology. Neuronal storage materials are thought to be largely glycolipid, ganglioside GM2. In the preliminary study, cholesterol accumulation has been demonstrated in neurons. So far defective transport of exogenous cholesterol has been demonstrated only in cultured NPC fibroblasts. We hypothesize that similar defect can be detected in neurons and in Aim 4, the hypothesis will be tested using cerebellar and/or hippocampal slice culture. Neurons in NPC die of apoptosis. Our preliminary studies have shown increasing expression of TNF-

10

Leukodystrophy

alphamRNA and intracellular proteins associated with death domain were upregulated, suggesting significant role of TNF-alpha in apoptotic neurodegeneration. Recent studies indicate that TNF-alpha promotes neurodegeneration through inhibition of survival signals activated by insulin-like growth factor receptor. Therefore, in Aim 5 possible protective role of insulin-like growth factor for neuronal degeneration will be tested by interbreeding NPC mouse with IGF-I transgenic mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY OF CANAVAN DISEASE Principal Investigator & Institution: Seashore, Margretta R.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GLOBOID CELL LEUKODYSTROPHY Principal Investigator & Institution: Singh, Avtar K.; Pathology and Lab Medicine; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 12-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim from the Applicant's Abstract) Globoid cell leukocystorophy (Krabbe's Disease) is an autosomal metqabolic disordear of beta-galactocerebrosidase deficiency with progressive pathognomonic accumulation of psychosine (galactosylsphingosine) which subsequently becomes a neuroinflammatory disease resulting in demyelination, olidogendrocyte loss and death. The objectives of the proposed studies are to elucidate the possible role of psychosine in neuroinflammatory response and in the mechanism of oligodendrocyte loss by using twitcher mice, a murine model of globoid cell leukodystrophy (GLD). Studies from our laboratory have demonstrated the psychosine potentiates the cytokine-induced induction of iNOS and also the psychosine when incubated with C6 glial cells in culture, induces apoptotic cell loss. Achievement of these goals will be facilitated by understanding the molecular mechanism of induction of inducible nitric oxide synthase (iNOS) and inflammatory cytokines (e.g. TNFalpha and IL-6) and psychosine-induced apoptotic loss of oligodendrocytes. Studies are also proposed to investigate the psychosine-induced electrophysiological alterations in brain cells/brain slices form twitcher mice. We also propose to test the efficacy of antioxidants (N-acetyl cysteine, alpha-lipoic acid) and the compounds that are known to block the induction of inflammatory cytokines (lovastatin, sodium phenylacetate) for halting/delaying the disease process in twitcher mice. The proposed studies will provide a better understanding of the disease process in GLD/twitcher mice and the demonstration of beneficial effects of the drugs in twitcher mice) may help in the identification of an ideal candidate drug for subsequent use in clinical trials involving GLD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: KRABBE DISEASE-MOLECULAR ANALYSIS AND TREATMENT Principal Investigator & Institution: Wenger, David A.; Prof of Med, Div of Medical Genetics; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-SEP-1986; Project End 28-FEB-2007

Studies

11

Summary: (provided by applicant): Krabbe disease or globoid cell leukodystrophy is a severe disorder of CNS and PNS myelin caused by mutations in the gene coding for galactocerebrosidase (GALC). The accumulation of one substrate, psychosine, is cytotoxic and induces the apoptotic death of oligodendrocytes (OLG) in the CNS and Schwann cells in the PNS. This is a project to treat murine and canine models using several approaches, including gene therapy and stem cell transplantation. A new transgenic mouse model (trs5O2) with low GALC activity was generated and will be utilized in some treatment studies. These mice live longer than twitcher (twi) mice and have large litters resulting in more affected pups for study. Recent studies show that the human GALC is not efficiently processed in rodent tissues so mouse GALC (mGALC) cDNA will be cloned into several viral vectors, including MFG, AAV and avian C-type retrovirus (SNV) for in vivo and ex vivo gene therapy trials. Insulin-like growth factor-I (IGF-1) has been shown to induce the proliferation of OLG progenitors, to increase remyelination after chemical or viral insults, and to prevent apoptotic death of OLG. Therefore, successful treatment of this disease may require delivery of GALC activity to prevent psychosine accumulation plus IGF-I to prevent apoptotic cell death and to induce remyelination. Initially IGF-1 will be injected subcutaneously in trsSO2 and twi mice to evaluate its effect clinically, biochemically and pathologically. A bi-cistronic viral vector containing mGALC cDNA plus IGF-I cDNA will be constructed in order to supply GALC activity plus IGF-1 to induce remyelination. A transgenic mouse that expresses IGF-1 under control of the myelin basic promoter will be generated and mated with GALC deficient mice to investigate its role in inducing remyelination when GALC activity is supplied via gene therapy or stem cell transplantation. Transduced and untransduced hematopoietic stem cells will be transplanted in the mouse and canine models with IGF-l supplementation. The effect of L-cycloserine to prolong life of the munne and canine models will be investigated. Treated dogs will be followed clinically and monitored by MRI and biochemical and pathological studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC REGULATION IN THE ACUTE PHASE Principal Investigator & Institution: Ron, David; Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-FEB-1993; Project End 30-JUN-2003 Summary: Nutritional deprivation of cells plays an important role in human diseases ranging from stroke and ischemic heart disease to the cachexia of cancer and chronic infection. In addition to their ability to react to lack of specific nutrients, cells have evolved more general stress-response pathways that are activated by many forms of cellular malnutrition and other metabolic perturbations. The gene encoding the transcription factor CHOP/GADD153 is induced by a pathway that is activated when cells are deprived of oxygen, energy sources or essential amino-acids. Chop gene knockout in mice and other experiments indicate that this pathway regulates adaptation to malnutrition in terms of changes in cell growth, differentiation and programmed cell death. Therefore, there is reason to believe that manipulating this response may impact on a broad range of medical conditions associated with cellular malnutrition. The goal of this study is to identify components of the signaling pathways that regulate Chop expression in starved cells and, utilizing genetic tools, to define their role in effecting cellular adaptation to this stressful state. Previous experiments implicate a stress-signal emanating from the endoplasmic reticulum (ER) in Chop induction in response to nutritional and metabolic stress. We have cloned two novel murine genes that are candidates for playing a role in regulating responses to ER stress in mammalian cells.

12

Leukodystrophy

The first, Ire1, encodes a murine homologue of the yeast protein Ire1p, implicated in activating gene expression in response to ER stress in that organism. The second, Perk, plays a role in attenuating translation in response to the accumulation of unfolded proteins in the ER and as such would be expected to play a role in reducing stress in that compartment. We will examine the hypothesis that Ire1 positively regulates Chop expression whereas Perk, by attenuating ER stress, negatively regulates it. We will examine the consequences of interfering with signaling by these two proteins in the context of mouse models of human diseases associated with ER stress. These will include a stroke model, models for renal acute tubular necrosis and mouse models for Pelizaeus-Merzbacher Leukodystrophy. A screen for other genes regulating Chop's response to malnutrition will also be carried out and these new components of the pathway will be examined functionally in cellular assays. If successful, these studies will shed light on basic biological principles that regulate the function of the secretory pathway in mammalian cells and on a poorly understood but broadly-utilized stressresponse that is activated in many disease states. The anchoring of these studies in animal-based disease models will hopefully provide clues as to the likely outcome of interfering with the function of specific components of the pathway. This information will be invaluable for rational selection of targets for therapeutic interventions that rely on manipulating the cellular response to ER stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF THE DEMYLINATING DISORDER ADLD Principal Investigator & Institution: Fu, Ying-Hui; Associate Professor; Neurology; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2004 Summary: (Investigator's abstract): Autosomal dominant leukodystrophy (ADLD) is a rare adult-onset demyelinating disorder. We have identified 6 families with this disorder. Two of these are large pedigrees for whom a tremendous amount of clinical, neuroradiological and neuropathological data has been collected. Although these patients share many clinical features with other white matter disorders, unique neuropathological findings suggest that the genesis of this disorder neither resides in defects of structural myelin proteins nor fatty acid metabolism in peroxisomes. ADLD is not an immune disease like multiple sclerosis (MS). We've demonstrated that lesions in ADLD brain have dramatic reduction in astrocyte number and that the surviving astrocytic cells are morphologically very abnormal. We hypothesize that ADLD results from a defect that interferes with a unique element in the myelination process and that understanding of this defect may provide novel insights into the process of myelin maintenance and turnover. We have localized the gene causing ADLD in these two large families to chromosome 5q3 1. Fine mapping has further narrowed the region and a complete physical map predicts the gene to reside within 3 megabases, much of which has already been sequenced. Candidate gene identification and testing are underway. Some genes in the region have already been eliminated using various mutation analysis strategies. Several plausible candidates are currently being tested including a novel gene with multiple EGF-like domains. This proposal outlines a strategy for identifying and characterizing the gene. Available patient material, physical mapping reagents and genomic sequence position us well for accomplishing this goal. In addition, experiments will be pursued toward preliminary characterization of both the wild-type and mutant ADLD protein. Understanding the cause of this demyelinating disorder may yield clues to genetic factors that modulate the expression of acquired leukodystrophies.

Studies

13

Ultimately, discovery of a new element in the synthesis and maintenance of myelin may provide a novel target for compounds that may stimulate remyelination in more common disorders like MS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS IN NEURODEGENERATION Principal Investigator & Institution: Gow, Alexander; Pediatrics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The long term goals of this research are to define and characterize the molecular mechanisms by which missense mutations in proteins cause neurodegenerative disease. The accumulation of unfolded protein intermediates in various subcellular compartments is thought to underlie pathogenesis for a number of neurodegenerative diseases, including Alzheimers disease. A critical component of this research is the availability of patient data and well-defined animal models in mice so that full use can be made of the extensive tools available for genetic manipulation, such as gene ablation by homologous recombination and the introduction of heterologous transgenes. In Specific Aim number 1 an hypothesis that neurodegeneration stems from the accumulation of misfolded proteins in the endoplasmic reticulum will be tested in greater detail in vitro. These data will be correlated with disease severity in patients as determined by detailed clinical evaluation and in vitro transfection assays. Furthermore, autopsy specimens will be characterized at the levels of RNA, protein and immunocytochemistry to determine if pathogenesis in humans is similar to that in the animal models. In Specific Aim number 2 the pathogenesis of mutant mice, for which signaling pathways normally activated by protein accumulation have been disrupted in knockout mice, will be characterized in detail both molecularly and morphologically to provide a deeper understanding of the involvement of protein misfolding in neurodegenerative disease. In Specific Aim number 3 a number of important genes and proteins recently found to be activated by protein accumulation in the endoplasmic reticulum will be examined at the levels of RNA, protein and immunocytochemistry in mouse models of neurodegenerative disease to determine if protein misfolding activates similar signaling pathways to those identified by other investigators studying different cell types in in vitro systems. Furthermore, the identification of downstream target genes using microarray screens will be sought to identify and characterize the signaling pathways that are activated by unfolded proteins, and ultimately determine if a cell survives or dies. Together, these Aims are expected to identify important pathological processes stemming from protein accumulation and may lead to strategies that ameliorate disease severity. Moreover, the knowledge gained from these studies may be applicable to the amelioration of other neurodegenerative diseases for which protein misfolding is a cause but the genetic or metabolic defects are unknown. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MOLECULAR PATHOGENESIS OF MNGIE Principal Investigator & Institution: Hirano, Michio; Assistant Professor; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: Mitochondria are the main sources of energy in the cell. They are unique mammalian organelles because they contain their own DNA (mtDNA), whose genes encode components of the respiratory chain/oxidative phosphorylation system. They

14

Leukodystrophy

are essential for the normal functioning of all cells in the body, and are absolutely critical for the function of those tissues that are highly dependent on aerobic metabolism, including heart, skeletal muscle, and brain. Since 1988, single large-scale mtDNA rearrangements, more than 100 mtDNA point mutations, as well as mendelian-inherited multiple mtDNA deletions have been associated with human diseases. Mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with multiple deletions and depletion of mtDNA in skeletal muscle. The major clinical features are: ptosis, external ophthalmoparesis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and leukodystrophy. We mapped the disease to chromosome 22q13.32-qter and subsequently identified loss-of-function mutations in the thymidine phosphorylase (TP) gene as the cause of the disorder. With the support of a NIH grant, we have continued our investigation of MNGIE. Clinicians from around the world have sent us blood samples to test for defects in thymidine phosphorylase. To date, we have identified 51 MNGIE patients. All patients tested have shown very low or no detectable activity of thymidine phosphorylase in huffy coat samples. In addition, we have identified dramatic increases of thymidine levels in plasma from patients. These findings led us to hypothesize that elevated intracellular levels of thymidine cause alterations of mitochondrial nucleotide pools that, in turn, induce point mutations, multiple deletions, and depletion of mtDNA. To test our hypothesis, we propose to study this disorder in vivo using human autopsy samples and in vitro using fibroblasts from patients. In addition, we have produced thymidine phosphorylase knock-out mice as a model for MNGIE. Our proposed studies of the pathogenesis of MNGIE are likely to enhance our understanding of nucleotide metabolism and will likely lead to more rational therapies for this uncommon, but devastating illness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MR TRACKING OF MAGNETICALLY LABELED STEM CELLS IN CNS Principal Investigator & Institution: Bulte, Jeff W.; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant):Stem cells have the potential to treat and possibly cure a variety of disorders, particularly those of the central nervous system (CNS). To develop successful clinical therapies, the fate of these cells after grafting must be monitored in a noninvasive manner. Currently, there is a need to develop in vivo means to track transplanted cells to determine their survival and migration patterns. By attaching a magnetic tag to stem cells, we propose to follow their biodistribution in vivo using MR imaging. We hypothesize that MR monitoring of the extent of cell migration, including the local distribution within the CNS, will allow for optimization of stem cell transplantation protocols, and that the same strategy may eventually be pursued in humans. Specifically, we will label bone marrow stem cells and neural stem cells obtained from mouse embryonic stem (ES) cell lines. Our first aim is to optimize the magnetic labeling procedure using superparamagnetic iron oxides that are coated with a transfection agent. Following magnetic tagging, we will then graft labeled cells into the CNS or inject cells systemically into the following four animal models of neurodegenerative disease: a) Long Evans shaker rat model of dysmyelination (aim 2); b) Twitcher mouse model of globoid cell leukodystrophy (aim 3); c) Sindbis virus rat model of lower motor neuron disease (aim 4); and d) mouse model of Parkinson's disease (aim 5). These models are believed to represent human CNS diseases that are

Studies

15

likely candidates for future stem cell therapy. Using serial MR imaging of the same animal over time, unique information on the spatial temporal dynamics of cell migration can be obtained. Specifically, we aim to correlate the obtained MR contrast images with conventional histopathologic labeling and staining techniques for each differentiated cell type, to determine the extent of new myelination or dopaminergic neuron formation and the potential improvement in animal behavior. Upon the completion of our studies, we expect to demonstrate that MR tracking of magnetically labeled stem cells is a valid new technology for studying stem cell based therapies in the CNS, setting the stage for applying this technique in a clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MRI, MTI AND MRS AND MPS VII AND KRABBE DISEASE Principal Investigator & Institution: Vite, Charles H.; Clinical Studies; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 23-JUL-1998; Project End 31-MAR-2002 Summary: The MCSDA candidate is a Veterinary Neurologist interested in developing and applying NMR methods to study animal models of human neurodegenerative diseases. The candidates long-term goal is a career in biomedical research studying the pathophysiology and therapy of neurodegeneration in animal models of human disease using magnetic resonance imaging (MRI magnetization transfer imaging ((MTI) and magnetic resonance spectroscopy (MRS). A career development plan including coursework in MR physics and medical genetics, consistent interaction with the Metabolic Magnetic Resonance Research Computer Center, as well as a Research Plan with specific and testable hypotheses will provide the candidate with the training necessary to achieve scientific independence in the study of neurodegeneration. The Veterinary School of the University pf Pennsylvania and my mentor, Dr. Jerry Glickson, of the Medical School of the University of Pennsylvania, have enthusiastically pledged their support for the next three years of training. This application concerns the study of canine and murine animal models of lysosomal storage disorders: mucopolysaccharidosis (MPS) VII and globoid-cell leukodystrophy (GCL). Lysosomal storage disorders affect approximately 1/1500 humans and no effective therapy has yet been developed for those patients with central nervous system manifestations of disease. The effectiveness of bone marrow transplantation and neural progenitor cell transplantation in canine and murine models of these diseases has yielded promising data regarding the treatment of neurodegeneration. Indeed, bone marrow transplantation to treat these disorders in human patients is currently being pursued based on the success demonstrated in animal models. MRI, MTI, and MRS offer exciting potential for increased tissue characterization and can be used to determine, in vivo, whether neurodegeneration is progressing, has ceased to progress, or is regressing following therapy. Specifically, animal MR scanners will be used to collect MRI, MTI, and MRS data in order to compare volumetric data and the concentrations of specific MR detectable metabolites between affected and treated animals. The "gold standard" for the efficacy of treatment will be post mortem tissue anal analysis for enzyme and substrate activity. These post mortem data will be compared to volumetric data and to the concentrations of MR detectable metabolites in order to identify MR data which are highly correlated with effective therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

16

•

Leukodystrophy

Project Title: MUTATIONS AND BIOCHEMISTRY OF GFAP IN ALEXANDER DISEASE Principal Investigator & Institution: Brenner, Michael; Associate Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: Glial fibrillary acidic protein (GFAP) is an intermediate filament protein found almost exclusively in astrocytes. Our laboratory has recently shown that mutations in the coding region of the GFAP gene are associated with Alexander disease, a rare but usually fatal disorder of the central nervous system. This disease is characterized by the presence of protein aggregates which have GFAP as a primary constituent. Alexander disease has different clinical features depending on whether it presents in an infant, juvenile or adult, so it has been unclear whether it is a single disease or a family of diseases. Our previous work analyzed a sufficient number of infantile samples to suggest that GFAP mutations are responsible for many cases of this type. Specific Aim 1 of this proposal addresses the extent to which GFAP mutations are responsible for the juvenile and adult forms. It also seeks to discover if additional, novel, mutations might be found for infantile cases. An immediate clinical benefit of the results will be more efficient, less-invasive diagnosis of Alexander disease, and fetal testing for families for families who have previously had an affected child. In Specific Aim 2 the discovered mutations will be incorporated into expression vectors and transgenes so that their properties can be studied. In Specific Aim 3 some of the properties of the mutated form of GFAP will be examined that might account for its toxicity; it will be determined if the protein is preferentially incorporated into the protein aggregates, whether it is more stable than the wild type GFAP, and whether it is aberrantly phosphorylated. In Specific Aim 4 we seek to develop antibodies that will interact specifically with the mutant from the normal one. In addition to greater understanding of Alexander disease, these studies may provide insights into other protein aggregate disorders, like Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and cirrhosis of the liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NEUROBIOLOGY OF DISEASE IN CHILDREN CONFERENCES Principal Investigator & Institution: Maria, Bernard L.; Child Health; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2006 Summary: This grant application describes for symposia titled "Neurobiology of Disease in Children", to be held in conjunction with the 2001 to 2005 annual Child Neurology Society (CNS) meetings. Each of the conditions selected as symposia topicsleukodystrophy, tuberous sclerosis complex, neurofibromatosis, Rett syndrome, and Tourette syndrome- are significant to the child neurology community. The symposia directors are Dr. Hugo Moser (leukodystrophy) Dr. Steven Roach (tuberous sclerosis complex), Dr. Bruce Korf (neurofibromatosis), Dr. Alan Percy (Rett syndrome), and Dr. Harvey Singer (Tourette syndrome). CNS members will constitute the largest segment of the projected 100 to 150 attendees. The symposia will bring together clinicians, scientists, caregivers, and National Institutes of Health (NIH) program officers to determine how research findings can be translated to enhance clinical understanding and affect clinical practice. Moreover, symposia attendees will identify the clinical and basic research needed to advance diagnostic accuracy and develop safe and effective therapies for these disorders. In 1998, the NIH funded a symposium on Joubert

Studies

17

syndrome held as a satellite meeting of the annual CNS conference that will serve as a model for the proposed scientific sessions. The overall aims are (1) to review scientific advances and determine their relevance to current and future clinical practice in child neurology; (2) to coordinate efforts among various clinical and basic science disciplines lay organizations, and NIH to review current research initiatives and define future directions; and (3) to disseminate symposia proceedings to ensure that clinical and basic science disciplines are informed about scientific advances, current research initiatives, and future directions. We believe the "Neurobiology of Disease in Children" symposia will contribute to advancing the field of child neurology by facilitating the exchange of information and coordination of research efforts across disciplines and organizations. The project will help further develop a symposium model that may be applied to a broader range of conditions that affect the child's nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL THURINGIENSIS

ADP

RIBOSYLATING

TOXIN

FROM

BACILLUS

Principal Investigator & Institution: Tainer, John A.; Professor; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 14-AUG-2003 Summary: Abstract Crystals from two different proteins have been studied under this proposal: saposin B and the BTB domain. Saposin B (SapB): This is a small (80 amino acid) protein found in the human lysosome that activates cerebroside sulfate for metabolic breakdown by aryslsulfatase A. A genetic deficiency in SapB results in a variant form of metachromatic leukodystrophy, a fatal lipid storage disease. We have studied SapB crystals derived from both natural sources (pig kidney) and from recombinant expression (human SapB expressed in E. coli). We have seen good diffraction patterns extending to a resolution of 2.4 Angstroms at CHESS beamline A1 for crystals of the porcine protein. However, these crystals have proven difficult to reproduce, and we have since turned to the recombinant human protein. To date, we have only obtained small crystals (0.04 mm x 0.04 mm x 0.02 mm) from this material, and reflections to 10 Angstroms have been observed on beamline F2. We are currently optimizing the purification and crystallization of the protein. BTB domain: This is a autonomous transrepression domain found in 5-10% of zinc finger transcription factors, as well as in some actin-binding proteins. Many BTB domain proteins are involved in embryonic development or in cancer. We have obtained crystals of a selenomethionine form of the domain that diffracts to 1.9 Angstrom at CHESS F-2. We have collected a full, three wavelength MAD dataset on these crystals. The data were processed with the CHESS implementation of MOSFLM and SCALA (average Rsym = 4.3% with 10-fold redundancy, 99% completeness), and the selenium positions were determined with SHELXS. The phase calculations were done with SHARP, leading to an overall figure of merit of 0.72. The electron density maps were exceptionally clear, and we were able to generate a full atomic model of the domain within 2 days of calculating the maps. The structure has been refined with REFMAC, with excellent statistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGIONAL PRIMATE RESEARCH CENTER Principal Investigator & Institution: Whelton, Paul K.; Senior Vice President for Health Science; None; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-JUN-1978; Project End 30-APR-2003

18

Leukodystrophy

Summary: This application is a request for the support of the operation of the Tulane Regional Primate Research Center for the next five year period. The research will be done utilizing non-human primates most of which are produced at the Center from breeding colonies. The score of the research projects, although primarily in the area of infectious diseases, covers a range of biomedical disciplines. The proposed AIDS research will include studies of vaccines, the interaction of the IDS virus with other infectious agents, the pathogenesis of disease in the monkey including the transfer of virus form the mother to the fetus, the role of alcohol in the infectious process, and the role of the mucosal immune response. Gene therapy studies will test strategies for correcting globoid cell leukodystrophy, hemophilia B, cystic fibrosis, liver disease, and as a treatment for AIDS. Other infectious disease research will be done on Lyme borreliosis (antibiotic treatment and autoimmunity), malaria (severe cerebral disease and disease during pregnancy)< lymphatic filariasis, and pyelonephritis in diabetics. Other, non-infectious disease research projects will be done on neuropeptides, aging, opioids, and vascular injury with balloon catheters. In addition to the research junction of the Center, this grant will support breeding colonies of macaques. It will also provide support for this Center to serve as a resource for investigators from other institutions who have need to conduct research in non-human primates. The performance site of these activities will be at the Tulane Regional Primate Research Center in Covington, Louisiana. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NETWORKS

THE

IMPACT

OF

GFAP

MUTATIONS

UPON

FILAMENT

Principal Investigator & Institution: Quinlan, Roy; University of Durham Old Shire Hall Durham, Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: This proposal is in response to three very exciting and recent findings. The most described six distinct mutations in the intermediate filament protein, GFAP that cause Alexander's disease. The GFAP mutations disrupt intermediate filament organization in astrocyte and also cause the formation of protein inclusions called Rosenthal Fibres, the main histopathological feature of the disease. The inclusions comprise GFAP as well as protein chaperones including, alphabeta-crystallin. Data from my lab identified alphabeta-crystallin as an important intermediate filament associated protein and when mutated it also causes diseases typified by filament inclusions. The second exciting finding is therefore- intermediate filaments require alphabeta-crystallin to function efficiently and without mishap by preserving the individuality of intermediate filaments within filament networks. The formation of intermediate filament networks in cells is an important question and leads es to the third exciting finding-the cytoplasmic spacing of GFAP filaments in astrocytes is set by vimentin. So, other intermediate filament proteins determine a key aspect of the GFAP network. Alexander's disease, like other human diseases caused by mutated intermediate filament proteins. This research programme will establish how GFAP forms networks via Specific Aim 1: To determine the influence of specific GFAP mutations (R79C, R79H, R239H, R239C, and R416W) upon the structural characteristics and properties of GFAP filaments in vitro. Specific Aim 2; To determine the effect of the GFAP mutations upon filament associations and network formation in cells and tissues. Specific Aim 3: To determine the role of associated proteins, including chaperones in GFAP function in astrocytes. The long-term aim of this research is to identify feasible therapeutic strategies that can restore intermediate filament networks in diseased cells.

Studies

19

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 “leukodystrophy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for leukodystrophy in the PubMed Central database: •

Complementation of arylsulfatase A in somatic hybrids of metachromatic leukodystrophy and multiple sulfatase deficiency disorder fibroblasts. by Chang PL, Davidson RG.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350235

•

Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. by Biffi A, De Palma M, Quattrini A, Del Carro U, Amadio S, Visigalli I, Sessa M, Fasano S, Brambilla R, Marchesini S, Bordignon C, Naldini L.; 2004 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=385395

•

Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides. by Ichioka T, Kishimoto Y, Brennan S, Santos GW, Yeager AM.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305064

•

Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. by Zhang XL, Rafi MA, DeGala G, Wenger DA.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53488

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

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

20

Leukodystrophy

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

A 9-bp deletion (2320del9) on the background of the arylsulfatase A pseudodeficiency allele in a metachromatic leukodystrophy patient and in a patient with nonprogressive neurological symptoms. Author(s): Regis S, Filocamo M, Stroppiano M, Corsolini F, Caroli F, Gatti R. Source: Human Genetics. 1998 January; 102(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9490297

•

A mutation in the saposin A domain of the sphingolipid activator protein (prosaposin) gene results in a late-onset, chronic form of globoid cell leukodystrophy in the mouse. Author(s): Matsuda J, Vanier MT, Saito Y, Tohyama J, Suzuki K, Suzuki K. Source: Human Molecular Genetics. 2001 May 15; 10(11): 1191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11371512

•

A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia. Author(s): Tagawa A, Ono S, Inoue K, Hosoi N, Kaneda K, Suzuki M, Nagao K, Shimizu N. Source: Journal of the Neurological Sciences. 2001 January 15; 183(1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11166794

•

A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD). Author(s): Wrobe D, Henseler M, Huettler S, Pascual Pascual SI, Chabas A, Sandhoff K. Source: Journal of Inherited Metabolic Disease. 2000 February; 23(1): 63-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10682309

•

A SURF1 gene mutation presenting as isolated leukodystrophy. Author(s): Rahman S, Brown RM, Chong WK, Wilson CJ, Brown GK. Source: Annals of Neurology. 2001 June; 49(6): 797-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11409433

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.

Studies

21

•

A T > C transition causing a Leu > Pro substitution in a conserved region of the arylsulfatase A gene in a late infantile metachromatic leukodystrophy patient. Author(s): Regis S, Filocamo M, Stroppiano M, Corsolini F, Gatti R. Source: Clinical Genetics. 1997 July; 52(1): 65-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272717

•

A unique familial leukodystrophy with adult onset dementia and abnormal glycolipid storage: a new lysosomal disease? Author(s): Simon DK, Rodriguez ML, Frosch MP, Quackenbush EJ, Feske SK, Natowicz MR. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 August; 65(2): 251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9703182

•

Adult metachromatic leukodystrophy: three cases with normal nerve conduction velocities in a family. Author(s): Cengiz N, Ozbenli T, Onar M, Yildiz L, Ertas B. Source: Acta Neurologica Scandinavica. 2002 June; 105(6): 454-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12027835

•

Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of galactosylceramidase cDNA from four Japanese patients. Author(s): Furuya H, Kukita Y, Nagano S, Sakai Y, Yamashita Y, Fukuyama H, Inatomi Y, Saito Y, Koike R, Tsuji S, Fukumaki Y, Hayashi K, Kobayashi T. Source: Human Genetics. 1997 September; 100(3-4): 450-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272171

•

Adult onset Krabbe's leukodystrophy. Author(s): Duyff RF, Weinstein HC. Source: Acta Neurologica Scandinavica. 1998 June; 97(6): 420-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9669479

•

Adult onset Krabbe's leukodystrophy: a report of 2 cases. Author(s): Turazzini M, Beltramello A, Bassi R, Del Colle R, Silvestri M. Source: Acta Neurologica Scandinavica. 1997 December; 96(6): 413-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9449482

•

Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis. Author(s): Verghese J, Weidenheim K, Malik S, Rapin I. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 November; 9(6): 663-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453083

22

Leukodystrophy

•

Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia. Author(s): Fukutani Y, Noriki Y, Sasaki K, Isaki K, Kuriyama M, Kurosawa K, Ida H. Source: Psychiatry and Clinical Neurosciences. 1999 June; 53(3): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10459747

•

Alexander disease: a leukodystrophy caused by a mutation in GFAP. Author(s): Johnson AB. Source: Neurochemical Research. 2004 May; 29(5): 961-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15139294

•

Allogeneic bone marrow transplantation for infantile globoid-cell leukodystrophy (Krabbe's disease). Author(s): Caniglia M, Rana I, Pinto RM, Fariello G, Caruso R, Angioni A, Dionisi Vici C, Sabetta G, De Rossi G. Source: Pediatric Transplantation. 2002 October; 6(5): 427-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390432

•

Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Author(s): Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W. Source: Bone Marrow Transplantation. 2002 August; 30(4): 215-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203137

•

An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity. Author(s): Regis S, Filocamo M, Corsolini F, Caroli F, Keulemans JL, van Diggelen OP, Gatti R. Source: European Journal of Human Genetics : Ejhg. 1999 February-March; 7(2): 125-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10196694

•

Anaesthetic management in children with metachromatic leukodystrophy. Author(s): Hernandez-Palazon J. Source: Paediatric Anaesthesia. 2003 October; 13(8): 733-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535916

•

Ataxia, deafness, leukodystrophy: inherited disorder of the white matter in three related patients. Author(s): Leuzzi V, Rinna A, Gallucci M, Di Capua M, Dionisi-Vici C, Longo D, Bertini E. Source: Neurology. 2000 June 27; 54(12): 2325-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881263

Studies

23

•

Autosomal dominant childhood onset slowly progressive leukodystrophy--a Japanese family with spastic paraparesis, ataxia, mental deterioration, and skeletal abnormality. Author(s): Nomoto N, Iwasaki Y, Arasaki K, Fujioka T, Kurihara T, Wakata N. Source: Journal of the Neurological Sciences. 2004 June 15; 221(1-2): 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15178211

•

Biliary disease in metachromatic leukodystrophy. Author(s): Heier L, Daneman A, Lowden JA, Cutz E, Craw S, Martin DJ. Source: Pediatric Radiology. 1983; 13(6): 313-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6646883

•

Biochemical abnormalities of metachromatic leukodystrophy in an adult psychiatric population. Author(s): Mahon-Haft H, Stone RK, Johnson R, Shah S. Source: The American Journal of Psychiatry. 1981 October; 138(10): 1372-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6117201

•

Biochemical findings after bone marrow transplantation for metachromatic leukodystrophy: a preliminary report. Author(s): Ladisch S, Bayever E, Philippart M, Feig SA. Source: Birth Defects Orig Artic Ser. 1986; 22(1): 69-76. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3516243

•

Biochemical pathogenesis of genetic leukodystrophies: comparison of metachromatic leukodystrophy and globoid cell leukodystrophy (Krabbe's disease). Author(s): Suzuki K. Source: Neuropediatrics. 1984 September; 15 Suppl: 32-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6152811

•

Biochemical studies of metachromatic leukodystrophy in three siblings. Author(s): Norton WT, Poduslo SE. Source: Acta Neuropathologica. 1982; 57(2-3): 188-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7124346

•

Biochemical studies of the late infantile form of metachromatic leukodystrophy. Author(s): Poduslo SE, Miller K, Jang Y. Source: Acta Neuropathologica. 1982; 57(1): 13-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6896397

24

Leukodystrophy

•

Biopsy diagnosis of a case of adult onset orthochromatic leukodystrophy. Clinical and brain biopsy findings. Author(s): Calandriello L, Matteucci C, Bertini E, Medolago Albani L, Antonelli A, Manfredi M, Palladini G. Source: Italian Journal of Neurological Sciences. 1992 December; 13(9): 787-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1483862

•

Bipolar affective disorder heralding cerebral demyelination in adreno-myeloleukodystrophy. Author(s): Gothelf D, Levite R, Gadoth N. Source: Brain & Development. 2000 May; 22(3): 184-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10814902

•

Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. Author(s): Krivit W, Peters C, Shapiro EG. Source: Current Opinion in Neurology. 1999 April; 12(2): 167-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226749

•

Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome. Author(s): Krivit W, Aubourg P, Shapiro E, Peters C. Source: Current Opinion in Hematology. 1999 November; 6(6): 377-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546790

•

Bone marrow transplantation for late infantile metachromatic leukodystrophy: pathogenic investigation for graft rejection. Author(s): Nagai T, Kaneko T, Shichijou H, Karato T, Maruyama A, Tsuchiya Y. Source: Acta Paediatr Jpn. 1993 October; 35(5): 404-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8256624

•

Bone marrow transplantation in metachromatic leukodystrophy caused by saposin-B deficiency: a case report with a 3-year follow-up period. Author(s): Landrieu P, Blanche S, Vanier MT, Metral S, Husson B, Sandhoff K, Fischer A. Source: The Journal of Pediatrics. 1998 July; 133(1): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9672525

Studies

25

•

Bone marrow transplantation in metachromatic leukodystrophy. Author(s): Lipton M, Lockman LA, Ramsay NK, Kersey JH, Jacobson RI, Krivit W. Source: Birth Defects Orig Artic Ser. 1986; 22(1): 57-67. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2870748

•

Brain lysosomal enzymes in generalized gangliosidosis and metachromatic leukodystrophy. Author(s): Den Tandt WR, Hooghwinkel GJ. Source: Acta Neurol (Napoli). 1980 February; 2(1): 10-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6156575

•

Canavan's leukodystrophy is associated with defects in cochlear neurodevelopment and deafness. Author(s): Ishiyama G, Lopez I, Baloh RW, Ishiyama A. Source: Neurology. 2003 May 27; 60(10): 1702-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771274

•

Canavan's spongiform leukodystrophy: a clinical anatomy of a genetic metabolic CNS disease. Author(s): Baslow MH. Source: Journal of Molecular Neuroscience : Mn. 2000 October; 15(2): 61-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220786

•

Case report: four-year follow-up of bone-marrow transplantation in late juvenile metachromatic leukodystrophy. Author(s): Navarro C, Dominguez C, Fernandez JM, Fachal C, Alvarez M. Source: Journal of Inherited Metabolic Disease. 1995; 18(2): 157-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7564234

•

Cerebral white-matter changes suggesting leukodystrophy in ataxia telangiectasia. Author(s): Chung EO, Bodensteiner JB, Noorani PA, Schochet SS Jr. Source: Journal of Child Neurology. 1994 January; 9(1): 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7512106

•

Characteristics of the dementia in late-onset metachromatic leukodystrophy. Author(s): Shapiro EG, Lockman LA, Knopman D, Krivit W. Source: Neurology. 1994 April; 44(4): 662-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8164821

26

Leukodystrophy

•

Characterization of four arylsulfatase A missense mutations G86D, Y201C, D255H, and E312D causing metachromatic leukodystrophy. Author(s): Hermann S, Schestag F, Polten A, Kafert S, Penzien J, Zlotogora J, Baumann N, Gieselmann V. Source: American Journal of Medical Genetics. 2000 March 6; 91(1): 68-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10751093

•

Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate. Author(s): Luzi P, Rafi MA, Victoria T, Baskin GB, Wenger DA. Source: Genomics. 1997 June 1; 42(2): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9192853

•

Characterization of two arylsulfatase A missense mutations D335V and T274M causing late infantile metachromatic leukodystrophy. Author(s): Hess B, Kafert S, Heinisch U, Wenger DA, Zlotogora J, Gieselmann V. Source: Human Mutation. 1996; 7(4): 311-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723680

•

Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray ionization-tandem mass spectrometry. Author(s): Whitfield PD, Sharp PC, Johnson DW, Nelson P, Meikle PJ. Source: Molecular Genetics and Metabolism. 2001 May; 73(1): 30-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11350180

•

Chemical compositions of brain and myelin in two patients with multiple sulphatase deficiency (a variant form of metachromatic leukodystrophy). Author(s): Eto Y, Meier C, Herschkowitz NN. Source: Journal of Neurochemistry. 1976 November; 27(5): 1071-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170590

•

Clinical and neuroradiological findings in classic infantile and late-onset globoid-cell leukodystrophy (Krabbe disease). Author(s): Barone R, Bruhl K, Stoeter P, Fiumara A, Pavone L, Beck M. Source: American Journal of Medical Genetics. 1996 May 3; 63(1): 209-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723112

•

Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. Author(s): Schwankhaus JD, Katz DA, Eldridge R, Schlesinger S, McFarland H. Source: Archives of Neurology. 1994 August; 51(8): 757-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8042923

Studies

27

•

Clinical manifestations of late onset cerebral storage disease: a case of metachromatic leukodystrophy. Author(s): Minauf M, Kleinert R, Ebner F. Source: Padiatr Padol. 1993; 28(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8446426

•

Clinical symptoms of adult metachromatic leukodystrophy and arylsulfatase A pseudodeficiency. Author(s): Hageman AT, Gabreels FJ, de Jong JG, Gabreels-Festen AA, van den Berg CJ, van Oost BA, Wevers RA. Source: Archives of Neurology. 1995 April; 52(4): 408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7710377

•

Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers. Author(s): Victoria T, Rafi MA, Wenger DA. Source: Genomics. 1996 May 1; 33(3): 457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8661004

•

Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity. Author(s): Berger J, Gmach M, Mayr U, Molzer B, Bernheimer H. Source: Human Mutation. 1999; 13(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9888390

•

Complex arylsulfatase A alleles causing metachromatic leukodystrophy. Author(s): Kappler J, Sommerlade HJ, von Figura K, Gieselmann V. Source: Human Mutation. 1994; 4(2): 119-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981715

•

Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease. Author(s): Penzien JM, Kappler J, Herschkowitz N, Schuknecht B, Leinekugel P, Propping P, Tonnesen T, Lou H, Moser H, Zierz S, et al. Source: American Journal of Human Genetics. 1993 March; 52(3): 557-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8095368

28

Leukodystrophy

•

Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity. Author(s): Regis S, Corsolini F, Stroppiano M, Cusano R, Filocamo M. Source: Human Genetics. 2002 April; 110(4): 351-5. Epub 2002 March 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11941485

•

Correction of the galactocerebrosidase deficiency in globoid cell leukodystrophycultured cells by SL3-3 retroviral-mediated gene transfer. Author(s): Gama Sosa MA, de Gasperi R, Undevia S, Yeretsian J, Rouse SC 2nd, Lyerla TA, Kolodny EH. Source: Biochemical and Biophysical Research Communications. 1996 January 26; 218(3): 766-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8579588

•

Defective oligomerization of arylsulfatase a as a cause of its instability in lysosomes and metachromatic leukodystrophy. Author(s): von Bulow R, Schmidt B, Dierks T, Schwabauer N, Schilling K, Weber E, Uson I, von Figura K. Source: The Journal of Biological Chemistry. 2002 March 15; 277(11): 9455-61. Epub 2002 January 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777924

•

Defective sulfatide synthesis in Krabbe's disease (globoid leukodystrophy). Author(s): Austin J, Bachhawat B, Armstrong D, Stumpf D, Kretschmer L, Mitchell C, Van Zee B. Source: Journal of Neuropathology and Experimental Neurology. 1968 January; 27(1): 141-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5656559

•

Defective sulfatide synthesis in Krabbe's disease (globoid leukodystrophy). Author(s): Austin J, Armstrong D, Stumpf D, Kretschmer L, Mitchell C, Van Zee B. Source: Trans Am Neurol Assoc. 1967; 92: 175-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5634024

•

Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome. Author(s): Burgeois M, Goutieres F, Chretien D, Rustin P, Munnich A, Aicardi J. Source: Brain & Development. 1992 November; 14(6): 404-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1492653

Studies

29

•

Deficiency in complex IV (cytochrome c oxidase) of the respiratory chain, presenting as a leukodystrophy in two siblings with Leigh syndrome. Author(s): Zafeiriou DI, Koletzko B, Mueller-Felber W, Paetzke I, Kueffer G, Jensen M. Source: Brain & Development. 1995 March-April; 17(2): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7625545

•

Dementia with impaired temporal glucose metabolism in late-onset metachromatic leukodystrophy. Author(s): Johannsen P, Ehlers L, Hansen HJ. Source: Dementia and Geriatric Cognitive Disorders. 2001 March-April; 12(2): 85-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11173879

•

Demonstration of specific storage material within cutaneous nerves in metachromatic leukodystrophy. Author(s): Gebhart W, Lassmann H, Niebauer G. Source: Journal of Cutaneous Pathology. 1978 February; 5(1): 5-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=77283

•

Demyelinating leukodystrophy with total cortical cerebellar atrophy. Author(s): Thulin B, McTaggart D, Neubuerger KT. Source: Archives of Neurology. 1968 February; 18(2): 113-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5636066

•

Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy. Author(s): Rafi MA, Zhang XL, DeGala G, Wenger DA. Source: Biochemical and Biophysical Research Communications. 1990 January 30; 166(2): 1017-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2302219

•

Detection of arylsulfatase A in leukocytes and urines of late infantile metachromatic leukodystrophy. Report of 3 cases. Author(s): Wang DF, Zhao KW, Zeng JS, Li LQ, Sun YX, Gao QZ. Source: Chinese Medical Journal. 1988 November; 101(11): 793-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2907984

•

Detection of donor lymphocytes in the cerebrospinal fluid of a patient with metachromatic leukodystrophy following bone marrow transplantation. Author(s): Yazaki M, Ohno T, Matsubayashi T, Yamada K, Osaka Y, Yamamori K, Ishikawa T, Wada Y, Sakuraba H. Source: Bone Marrow Transplantation. 1995 January; 15(1): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7742747

30

Leukodystrophy

•

Detection of homozygotes and heterozygotes for metachromatic leukodystrophy in lymphoid cell lines and peripheral leukocytes. Author(s): Beratis NG, Danesino C, Hirschhorn K. Source: Annals of Human Genetics. 1975 May; 38(4): 485-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1238048

•

Determination of lysosomal enzymes in saliva. Confirmation of the diagnosis of metachromatic leukodystrophy and fucosidosis by enzyme analysis. Author(s): Den Tandt WR, Jaeken J. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1979 September 15; 97(1): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=40713

•

Diagnostic techniques in metachromatic leukodystrophy. Author(s): Julius R, Buehler B, Aylsworth A, Petery LS, Rennert O, Greer M. Source: Neurology. 1971 January; 21(1): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4099955

•

Diffuse cerebral sclerosis, melanoderma and adrenal insufficiency (adrenoleukodystrophy). Author(s): Hormia M. Source: Acta Neurologica Scandinavica. 1978 August; 58(2): 128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=707040

•

Diffuse leukodystrophy in an infant with cytochrome-c oxidase deficiency. Author(s): Harpey JP, Heron D, Prudent M, Charpentier C, Rustin P, Ponsot G, CormierDaire V. Source: Journal of Inherited Metabolic Disease. 1998 October; 21(7): 748-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9819704

•

Diffuse leukodystrophy with a large-scale mitochondrial DNA deletion. Author(s): Nakai A, Goto Y, Fujisawa K, Shigematsu Y, Kikawa Y, Konishi Y, Nonaka I, Sudo M. Source: Lancet. 1994 June 4; 343(8910): 1397-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7910887

•

Discrimination between metachromatic leukodystrophy and pseudo-deficiency of arylsulfatase A by restriction digest of amplified gene fragments. Author(s): Ben-Yoseph Y, Mitchell DA. Source: The American Journal of the Medical Sciences. 1995 February; 309(2): 88-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7847447

Studies

31

•

Disease-causing mutations in cis with the common arylsulfatase A pseudodeficiency allele compound the difficulties in accurately identifying patients and carriers of metachromatic leukodystrophy. Author(s): Rafi MA, Coppola S, Liu SL, Rao HZ, Wenger DA. Source: Molecular Genetics and Metabolism. 2003 June; 79(2): 83-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809637

•

Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: a new entity? Author(s): Fukazawa T, Sasaki H, Kikuchi S, Hamada K, Hamada T, Tashiro K. Source: Journal of Neurology. 1997 July; 244(7): 446-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9266464

•

Early onset leukodystrophy with distinct facial features in 2 siblings. Author(s): Harbord MG, Finn JP, Hall-Craggs MA, Brett EM, Baraitser M. Source: Neuropediatrics. 1989 August; 20(3): 154-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2779744

•

Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy. Author(s): Salmon E, Van der Linden M, Maerfens Noordhout A, Brucher JM, Mouchette R, Waltregny A, Degueldre C, Franck G. Source: Acta Neurol Belg. 1999 September; 99(3): 185-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10544727

•

Ehlers-Danlos syndrome type VIII and leukodystrophy. Author(s): Spranger S, Spranger M, Kirchhof K, Steinmann B. Source: American Journal of Medical Genetics. 1996 December 11; 66(2): 239-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8958339

•

Electroencephalographic findings in a case of globoid cell leukodystrophy. Author(s): Iinuma K, Onuma A. Source: The Tohoku Journal of Experimental Medicine. 1975 January; 115(1): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1129760

•

Electron microscopic investigation of inclusion material in a case of adult metachromatic leukodystrophy; observations on kidney biopsy, peripheral nerve and cerebral white matter. Author(s): Joosten E, Hoes M, Gabreels-Festen A, Hommes O, Schuurmans Stekhoven H, Slooff JL. Source: Acta Neuropathologica. 1975 December 8; 33(2): 165-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=173129

32

Leukodystrophy

•

Electrophoresis of arylsulfatase from normal individuals and patients with metachromatic leukodystrophy. Author(s): Rattazzi MC, Marks JS, Davidson RG. Source: American Journal of Human Genetics. 1973 May; 25(3): 310-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4704863

•

Elevated sulfatide excretion in compound heterozygotes of metachromatic leukodystrophy and ASA-pseudodeficiency allele. Author(s): Lugowska A, Tylki-Szymanska A, Berger J, Molzer B. Source: Clinical Biochemistry. 1997 June; 30(4): 325-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9209791

•

Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy: dependence on reduction of arylsulfatase A activity. Author(s): Molzer B, Sundt-Heller R, Kainz-Korschinsky M, Zobel M. Source: American Journal of Medical Genetics. 1992 November 1; 44(4): 523-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1359786

•

Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy. Author(s): Bambach BJ, Moser HW, Blakemore K, Corson VL, Griffin CA, Noga SJ, Perlman EJ, Zuckerman R, Wenger DA, Jones RJ. Source: Bone Marrow Transplantation. 1997 February; 19(4): 399-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9051254

•

Enzymatic abnormality of the carrier state in metachromatic leukodystrophy. Author(s): Taniguchi N, Nanba I. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1970 September; 29(3): 375-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5496557

•

Enzymic detection of metachromatic leukodystrophy patients and heterozygotes. Author(s): Jordan TW, Casey B, Weston HJ. Source: N Z Med J. 1977 May 11; 85(587): 369-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=23508

•

Enzymic studies of sulphatases in tissues of the normal human and in metachromatic leukodystrophy with multiple sulphatase deficiencies: arylsulphatases A, B and C, cerebroside sulphatase, psychosine sulphatase and steroid sulphatases. Author(s): Eto Y, Rampini S, Wiesmann U, Herschkowitz NN. Source: Journal of Neurochemistry. 1974 December; 23(6): 1161-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4281441

Studies

33

•

Episodic coma in a new leukodystrophy. Author(s): Espay AJ, Bodensteiner JB, Patel H. Source: Pediatric Neurology. 2002 February; 26(2): 139-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897479

•

Evaluation of the metabolic defect in metachromatic leukodystrophy (MLD). Author(s): Moser H, Moser AB, McKhann GM. Source: Trans Am Neurol Assoc. 1967; 92: 171-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5634023

•

Evolution of neuronal changes in metachromatic leukodystrophy. An electron microscopic study. Author(s): Liu HM. Source: Acta Neuropathologica. 1973 January 30; 23(2): 133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4700611

•

Extensive brain calcifications, leukodystrophy, and formation of parenchymal cysts: a new progressive disorder due to diffuse cerebral microangiopathy. Author(s): Labrune P, Lacroix C, Goutieres F, de Laveaucoupet J, Chevalier P, Zerah M, Husson B, Landrieu P. Source: Neurology. 1996 May; 46(5): 1297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8628470

•

Familial Dandy-Walker malformation and leukodystrophy. Author(s): Humbertclaude VT, Coubes PA, Leboucq N, Echenne BB. Source: Pediatric Neurology. 1997 May; 16(4): 326-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9258968

•

Familial mitochondrial encephalomyopathy with deaf-mutism, ophthalmoplegia and leukodystrophy. Author(s): Nakagawa M, Kaminishi Y, Isashiki Y, Yamada H, Higuchi I, Uchida Y, Osame M. Source: Acta Neurologica Scandinavica. 1995 July; 92(1): 102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572054

•

Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Author(s): Black DN, Harris R, Schiffmann R, Wong K. Source: Neurology. 2002 January 8; 58(1): 161-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781442

34

Leukodystrophy

•

Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Author(s): Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, Fariello G, Bosman C, Santorelli FM, Boespflug-Tanguy O, Bertini E. Source: Neurology. 2001 July 24; 57(2): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468311

•

Fetal globoid cell leukodystrophy in one of twins. Author(s): Okeda R, Suzuki Y, Horiguchi S, Fujii T. Source: Acta Neuropathologica. 1979 July 13; 47(2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=474075

•

Fetal globoid cell leukodystrophy. Author(s): Pollanen MS, Brody BA. Source: Archives of Pathology & Laboratory Medicine. 1990 February; 114(2): 213-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2154169

•

Fetal Krabbe leukodystrophy. A morphologic study of two cases. Author(s): Martin JJ, Leroy JG, Ceuterick C, Libert J, Dodinval P, Martin L. Source: Acta Neuropathologica. 1981; 53(2): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7211207

•

Fetal metachromatic leukodystrophy: pathology, biochemistry and a study of in vitro enzyme replacement in CNS tissue. Author(s): Poduslo SE, Tennekoon G, Price D, Miller K, McKhann GM. Source: Journal of Neuropathology and Experimental Neurology. 1976 NovemberDecember; 35(6): 622-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11278

•

Fiber type disproportion in metachromatic leukodystrophy. Author(s): Krendel DA, Shutter LA, Holt PJ. Source: Muscle & Nerve. 1994 November; 17(11): 1352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7935562

•

First trimester prenatal diagnosis of metachromatic leukodystrophy on chorionic villi by 'immunoprecipitation-electrophoresis'. Author(s): Poenaru L, Castelnau L, Besancon AM, Nicolesco H, Akli S, Theophil D. Source: Journal of Inherited Metabolic Disease. 1988; 11(2): 123-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2902245

Studies

35

•

Further observations on the fine structure of globoid leukodystrophy. Peripheral neuropathy and optic nerve involvement. Author(s): Yunis EJ, Lee RE. Source: Human Pathology. 1972 September; 3(3): 371-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4114797

•

Galactosylceramide and galactosylsphingosine loading studies in cultured skin fibroblasts in human and murine globoid cell leukodystrophy. Author(s): Ida H, Kusano K, Suzuki H, Tokoro T, Eto Y. Source: Biochemical and Biophysical Research Communications. 1990 January 30; 166(2): 1053-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2302222

•

Gene therapy for metachromatic leukodystrophy. Author(s): Ohashi T, Watabe K, Sato Y, Saito I, Barranger JA, Matalon R, Eto Y. Source: Acta Paediatr Jpn. 1996 April; 38(2): 193-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8677802

•

Generation of a mouse with low galactocerebrosidase activity by gene targeting: a new model of globoid cell leukodystrophy (Krabbe disease). Author(s): Luzi P, Rafi MA, Zaka M, Curtis M, Vanier MT, Wenger DA. Source: Molecular Genetics and Metabolism. 2001 July; 73(3): 211-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11461188

•

Genetic complementation in somatic cell hybrids of cerebroside sulfatase activator deficiency and metachromatic leukodystrophy fibroblasts. Author(s): Kihara H, Tsay KK, Fluharty AL. Source: Human Genetics. 1984; 66(4): 300-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6144627

•

Genetic galactosylceramidase deficiency (globoid cell leukodystrophy, Krabbe disease) in different mammalian species. Author(s): Suzuki K, Suzuki K. Source: Neurochem Pathol. 1985 Spring; 3(1): 53-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3895053

•

Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31. Author(s): Coffeen CM, McKenna CE, Koeppen AH, Plaster NM, Maragakis N, Mihalopoulos J, Schwankhaus JD, Flanigan KM, Gregg RG, Ptacek LJ, Fu YH. Source: Human Molecular Genetics. 2000 March 22; 9(5): 787-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10749986

36

Leukodystrophy

•

Genetics of metachromatic leukodystrophy. Author(s): Gieselmann V, Kreysing J, von Figura K. Source: Gene Therapy. 1994; 1 Suppl 1: S87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8542433

•

Genotype assignments in a family with the pseudo arylsulfatase a deficiency trait without metachromatic leukodystrophy. Author(s): Kihara H, Meek WE, Fluharty AL. Source: Pediatric Research. 1984 October; 18(10): 1021-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6149514

•

Giant axonal neuropathy and leukodystrophy. Author(s): Stollhoff K, Albani M, Goebel HH. Source: Pediatric Neurology. 1991 January-February; 7(1): 69-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2029298

•

Globid leukodystrophy. II. Ultrastructure and chemical pathology. Author(s): Malone MJ, Szoke M, Davis DA. Source: Archives of Neurology. 1975 September; 32(9): 613-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1164213

•

Globoid cell leukodystrophy (Krabbe's disease). Metabolic studies with cultured fibroblasts. Author(s): Tanaka H, Suzuki K. Source: Journal of the Neurological Sciences. 1978 October; 38(3): 409-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=731265

•

Globoid cell leukodystrophy (Krabbe's disease): update. Author(s): Suzuki K. Source: Journal of Child Neurology. 2003 September; 18(9): 595-603. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572137

•

Globoid cell leukodystrophy in cairn and West Highland white terriers. Author(s): Wenger DA, Victoria T, Rafi MA, Luzi P, Vanier MT, Vite C, Patterson DF, Haskins MH. Source: The Journal of Heredity. 1999 January-February; 90(1): 138-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9987921

Studies

37

•

Globoid cell leukodystrophy is a generalized galactosylsphingosine (psychosine) storage disease. Author(s): Kobayashi T, Shinoda H, Goto I, Yamanaka T, Suzuki Y. Source: Biochemical and Biophysical Research Communications. 1987 April 14; 144(1): 41-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3579916

•

Globoid cell leukodystrophy: a family with both late-infantile and adult type. Author(s): Verdru P, Lammens M, Dom R, Van Elsen A, Carton H. Source: Neurology. 1991 September; 41(9): 1382-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1891085

•

Globoid cell leukodystrophy: comparison of neuropathology with magnetic resonance imaging. Author(s): Percy AK, Odrezin GT, Knowles PD, Rouah E, Armstrong DD. Source: Acta Neuropathologica. 1994; 88(1): 26-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7941969

•

Globoid cell leukodystrophy: deficiency of lactosyl ceramide beta-galactosidase. Author(s): Wenger DA, Sattler M, Hiatt W. Source: Proceedings of the National Academy of Sciences of the United States of America. 1974 March; 71(3): 854-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4522795

•

Globoid cell leukodystrophy: distinguishing early-onset from late-onset disease using a brain MR imaging scoring method. Author(s): Loes DJ, Peters C, Krivit W. Source: Ajnr. American Journal of Neuroradiology. 1999 February; 20(2): 316-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10094363

•

Glycosphingolipid beta-galactosidases. 3. Canine form of globoid cell leukodystrophy; comparison with the human disease. Author(s): Suzuki Y, Miyatake T, Fletcher TF, Suzuki K. Source: The Journal of Biological Chemistry. 1974 April 10; 249(7): 2109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4818826

•

Glycosphingolipid beta-galactosidases. II. Electrofocusing characterization of the enzymes in human globoid cell leukodystrophy (Krabbe's disease). Author(s): Suzuki Y, Suzuki K. Source: The Journal of Biological Chemistry. 1974 April 10; 249(7): 2105-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4818825

38

Leukodystrophy

•

Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. Author(s): Krivit W, Shapiro EG, Peters C, Wagner JE, Cornu G, Kurtzberg J, Wenger DA, Kolodny EH, Vanier MT, Loes DJ, Dusenbery K, Lockman LA. Source: The New England Journal of Medicine. 1998 April 16; 338(16): 1119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9545360

•

Hemorrhagic cholecystitis as a likely cause of nontraumatic hemobilia in metachromatic leukodystrophy: report of a case. Author(s): Vettoretto N, Giovanetti M, Regina P, Baronchelli C, Giulini SM. Source: Ann Ital Chir. 2001 November-December; 72(6): 725-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061226

•

Hepatic galactosylceramide in globoid cell leukodystrophy (Krabbe's disease). Author(s): Dawson G. Source: Lipids. 1973 March; 8(3): 154-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4692883

•

Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. Author(s): Eldridge R, Anayiotos CP, Schlesinger S, Cowen D, Bever C, Patronas N, McFarland H. Source: The New England Journal of Medicine. 1984 October 11; 311(15): 948-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6472420

•

Heterogeneity in late-onset metachromatic leukodystrophy. Effect of inhibitors of cysteine proteinases. Author(s): von Figura K, Steckel F, Conary J, Hasilik A, Shaw E. Source: American Journal of Human Genetics. 1986 September; 39(3): 371-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2876627

•

High prevalence of I179S mutation in patients with late-onset metachromatic leukodystrophy. Author(s): Lugowska A, Berger J, Tylki-Szymanska A, Czartoryska B, Loschl B, Molzer B. Source: Clinical Genetics. 2002 May; 61(5): 389-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081727

•

High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy. Author(s): Kreysing J, Bohne W, Bosenberg C, Marchesini S, Turpin JC, Baumann N, von Figura K, Gieselmann V. Source: American Journal of Human Genetics. 1993 August; 53(2): 339-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8101038

Studies

39

•

Histochemical and biochemical studies of urinary lipids in metachromatic leukodystrophy and Fabry's disease. Author(s): Pilz H, Muller D, Linke I. Source: The Journal of Laboratory and Clinical Medicine. 1973 January; 81(1): 7-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4565559

•

Histochemical, ultrastructural and biochemical studies of a case with leukodystrophy due to congenital deficiency of myelin. Author(s): Adachi M, Schneck L, Torii J, Volk BW. Source: Journal of Neuropathology and Experimental Neurology. 1970 October; 29(4): 601-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5471924

•

Histopathological and ultrastructural study of a case of infantile metachromatic leukodystrophy. Author(s): Fenzi F, Moretto G, Maleci A, Galiazzo Rizzuto S, Dalla Bernardina B, Bondavalli S, Rizzuto N. Source: Italian Journal of Neurological Sciences. 1983 December; 4(4): 503-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6325371

•

HPLC analysis of urinary sulfatide: an aid in the diagnosis of metachromatic leukodystrophy. Author(s): Strasberg PM, Warren I, Skomorowski MA, Lowden JA. Source: Clinical Biochemistry. 1985 April; 18(2): 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2861921

•

Human urinary sulfatides in patients with sulfatidosis (metachromatic leukodystrophy). Author(s): Philippart M, Sarlieve L, Meurant C, Mechler L. Source: Journal of Lipid Research. 1971 July; 12(4): 434-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5164093

•

Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients. Author(s): Gort L, Coll MJ, Chabas A. Source: Human Mutation. 1999; 14(3): 240-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10477432

40

Leukodystrophy

•

Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy. Author(s): Kondo R, Wakamatsu N, Yoshino H, Fukuhara N, Miyatake T, Tsuji S. Source: American Journal of Human Genetics. 1991 May; 48(5): 971-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1673291

•

Identification of nine novel arylsulfatase a (ARSA) gene mutations in patients with metachromatic leukodystrophy (MLD). Author(s): Eng B, Nakamura LN, O'Reilly N, Schokman N, Nowaczyk MM, Krivit W, Waye JS. Source: Human Mutation. 2003 November; 22(5): 418-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517960

•

Identification of seven novel mutations associated with metachromatic leukodystrophy. Author(s): Barth ML, Fensom A, Harris A. Source: Human Mutation. 1995; 6(2): 170-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7581401

•

Immunohistological study of globoid cell leukodystrophy. Author(s): Itoh M, Hayashi M, Fujioka Y, Nagashima K, Morimatsu Y, Matsuyama H. Source: Brain & Development. 2002 August; 24(5): 284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12142065

•

Immuno-lectin histochemistry and ultrastructure in two cases of globoid cell leukodystrophy (Krabbe's disease). Author(s): Figols J, Zimmer C, Warzok R, Cervos-Navarro J. Source: Clin Neuropathol. 1992 November-December; 11(6): 312-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1335383

•

Immunologic studies of arylsulfatase A in normal and metachromatic leukodystrophy liver. Author(s): Shapira E, DeGregorio RR, Nadler HL. Source: Pediatric Research. 1978 March; 12(3): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=25410

•

Immunological studies of sulfatase A in normals and in metachromatic leukodystrophy. Author(s): Stumpf D, Neuwelt E, Austin J, Kohler P. Source: Trans Am Neurol Assoc. 1971; 96: 80-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5159132

Studies

41

•

Importance of the glycosylation and polyadenylation variants in metachromatic leukodystrophy pseudodeficiency phenotype. Author(s): Harvey JS, Carey WF, Morris CP. Source: Human Molecular Genetics. 1998 August; 7(8): 1215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9668161

•

Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy. Author(s): Solders G, Celsing G, Hagenfeldt L, Ljungman P, Isberg B, Ringden O. Source: Bone Marrow Transplantation. 1998 December; 22(11): 1119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9877277

•

In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Author(s): Consiglio A, Quattrini A, Martino S, Bensadoun JC, Dolcetta D, Trojani A, Benaglia G, Marchesini S, Cestari V, Oliverio A, Bordignon C, Naldini L. Source: Nature Medicine. 2001 March; 7(3): 310-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231629

•

Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Author(s): Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J, Hoffman EP, Naidu S. Source: Neurology. 2004 March 23; 62(6): 878-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037685

•

Infantile and fetal globoid cell leukodystrophy: analysis of galactosylceramide and galactosylsphingosine. Author(s): Kobayashi T, Goto I, Yamanaka T, Suzuki Y, Nakano T, Suzuki K. Source: Annals of Neurology. 1988 October; 24(4): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3239954

•

Infantile familial encephalopathy with cerebral calcifications and leukodystrophy. Author(s): Razavi-Encha F, Larroche JC, Gaillard D. Source: Neuropediatrics. 1988 May; 19(2): 72-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3287208

•

Infantile metachromatic leukodystrophy. Confirmation of a prenatal diagnosis. Author(s): Leroy JG, Van Elsen AF, Martin JJ, Dumon JE, Hulet AE, Okada S, Navarro C. Source: The New England Journal of Medicine. 1973 June 28; 288(26): 1365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4707419

42

Leukodystrophy

•

Inheritance of metachromatic leukodystrophy. Author(s): Langenbeck U, Dunker P, Heipertz R, Pilz H. Source: American Journal of Human Genetics. 1977 November; 29(6): 639-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=930929

•

Inheritance of the enzyme deficiency in three neurolipidoses: variant 0 of Tay-Sachs disease (Sandhoff's disease), classic Tay-Sachs disease, and metachromatic leukodystrophy. Identification of the heterozygous carriers. Author(s): Harzer K. Source: Humangenetik. 1973; 20(1): 9-24. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4776531

•

Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency. Author(s): Zhang XL, Rafi MA, DeGala G, Wenger DA. Source: Proceedings of the National Academy of Sciences of the United States of America. 1990 February; 87(4): 1426-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1689485

•

Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophy. Author(s): Tylki-Szymanska A, Lugowska A, Chmielik J, Kotowicz J, JakubowskaWinecka A, Zobel M, Berger J, Molzer B. Source: American Journal of Medical Genetics. 2002 July 15; 110(4): 315-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12116203

•

Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutation. Author(s): Coulter-Mackie MB, Applegarth DA, Toone JR, Gagnier L, Anzarut AR, Hendson G. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2002 May; 29(2): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035837

•

Juvenile and adult metachromatic leukodystrophy: partial restoration of arylsulfatase A (cerebroside sulfatase) activity by inhibitors of thiol proteinases. Author(s): von Figura K, Steckel F, Hasilik A. Source: Proceedings of the National Academy of Sciences of the United States of America. 1983 October; 80(19): 6066-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6136972

Studies

43

•

Juvenile Krabbe's Leukodystrophy precipitated by influenza A infection. Author(s): McGuinness OE, Winrow AP, Smyth DP. Source: Developmental Medicine and Child Neurology. 1996 May; 38(5): 460-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8698154

•

Juvenile metachromatic leukodystrophy. Clinical, biochemical, and neuropathologic studies in nine new cases. Author(s): Haltia T, Palo J, Haltia M, Icen A. Source: Archives of Neurology. 1980 January; 37(1): 42-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6101304

•

Juvenile metachromatic leukodystrophy: deficiency of an arylsufatase A component. Author(s): Suzuki Y, Mizuno Y. Source: The Journal of Pediatrics. 1974 December; 85(6): 823-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4422475

•

Juvenile metachromatic leukodystrophy: evoked potentials and computed tomography. Author(s): Carlin L, Roach ES, Riela A, Spudis E, McLean WT Jr. Source: Annals of Neurology. 1983 January; 13(1): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6830154

•

Juvenile metachromatic leukodystrophy: neurological outcome two years after bone marrow transplantation. Author(s): Guffon N, Souillet G, Maire I, Dorche C, Mathieu M, Guibaud P. Source: Journal of Inherited Metabolic Disease. 1995; 18(2): 159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7564235

•

Juvenile-onset metachromatic leukodystrophy: biochemical and electrophysiologic studies. Author(s): Clark JR, Miller RG, Vidgoff JM. Source: Neurology. 1979 March; 29(3): 346-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=36575

•

Kearns-Sayre syndrome. A case of the complete syndrome with encephalic leukodystrophy and calcification of basal ganglia. Author(s): Carboni P, Giacanelli M, Porro G, Sideri G, Paolella A. Source: Italian Journal of Neurological Sciences. 1981 August; 2(3): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7341548

44

Leukodystrophy

•

Kluver-Bucy syndrome caused by adreno-leukodystrophy. Author(s): Powers JM, Schaumburg HH, Gaffney CL. Source: Neurology. 1980 November; 30(11): 1231-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7191519

•

Krabbe globoid cell leukodystrophy. Electron microscopy shows characteristic inclusions in eccrine sweat glands. Author(s): Ceuterick C, Martin JJ. Source: Pathology, Research and Practice. 1993 May; 189(4): 384-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8394576

•

Krabbe's disease (globoid cell leukodystrophy): report of the first family in Thailand. Author(s): Chiemchanya S, Visudhiphan P, Chiuahriun S. Source: J Med Assoc Thai. 1976 December; 59(12): 567-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1010968

•

Krabbe's disease (globoid leukodystrophy). Electron microscopic observations. Author(s): Schochet SS Jr, Hardman JM, Lampert PW, Earle KM. Source: Arch Pathol. 1969 September; 88(3): 305-13. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5800929

•

Krabbe's disease: globoid cell leukodystrophy. Author(s): Jacob JC, Kutty KM, Islam M, Dominic RG, Dawson G. Source: Can Med Assoc J. 1973 June 2; 108(11): 1398-400. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4704908

•

Krabbe's globoid cell leukodystrophy: deficiency of glactocerebrosidase in serum, leukocytes, and fibroblasts. Author(s): Suzuki Y, Suzuki K. Source: Science. 1971 January 8; 171(966): 73-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5538703

•

Krabbe's leukocystrophy (globoid cell leukodystrophy). An ultrastructural study. Author(s): Suzuki K, Grover WD. Source: American Journal of Obstetrics and Gynecology. 1970 April 1; 106(7): 385-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5437261

•

Krabbe's leukodystrophy without globoid cells. Author(s): Dunn HG, Dolman CL, Farrell DF, Tischler B, Hasinoff C, Woolf LI. Source: Neurology. 1976 November; 26(11): 1035-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=988509

Studies

45

•

Late infantile form metachromatic leukodystrophy: report of one case. Author(s): Shian WJ, Chi CC, Mak SC, Tzeng GY. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1992 July-August; 33(4): 28693. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1296437

•

Late infantile metachromatic leukodystrophy in Israel. Author(s): Zlotogora J, Gieselman V, von Figura K, Zeigler M, Bach G. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1994; 48(8-9): 347-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7858169

•

Late juvenile metachromatic leukodystrophy treated with bone marrow transplantation; a 4-year follow-up study. Author(s): Navarro C, Fernandez JM, Dominguez C, Fachal C, Alvarez M. Source: Neurology. 1996 January; 46(1): 254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8559389

•

Late onset globoid cell leukodystrophy (Krabbe's disease)--Swedish case with 15 years of follow-up. Author(s): Arvidsson J, Hagberg B, Mansson JE, Svennerholm L. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 February; 84(2): 218-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7756815

•

Late onset globoid cell leukodystrophy. Author(s): Verdru P. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1992 October; 55(10): 980. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1431973

•

Late onset globoid cell leukodystrophy. Author(s): Grewal RP, Petronas N, Barton NW. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1991 November; 54(11): 1011-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1800646

•

Late onset Krabbe's leukodystrophy: a report of four cases. Author(s): Phelps M, Aicardi J, Vanier MT. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1991 April; 54(4): 293-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2056315

46

Leukodystrophy

•

Late-onset globoid cell leukodystrophy mimicking an infiltrating glioma. Author(s): Epstein MA, Zimmerman RA, Rorke LB, Sladky JT. Source: Pediatric Radiology. 1991; 21(2): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2027716

•

Late-onset metachromatic leukodystrophy clinically presenting as isolated peripheral neuropathy: compound heterozygosity for the IVS2+1G-->A mutation and a newly identified missense mutation (Thr408Ile) in a Spanish family. Author(s): Comabella M, Waye JS, Raguer N, Eng B, Dominguez C, Navarro C, Borras C, Krivit W, Montalban X. Source: Annals of Neurology. 2001 July; 50(1): 108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11456299

•

Late-onset metachromatic leukodystrophy: molecular pathology in two siblings. Author(s): Kappler J, von Figura K, Gieselmann V. Source: Annals of Neurology. 1992 March; 31(3): 256-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1353340

•

Leukodystrophy and bone marrow transplantation: role of mixed hematopoietic chimerism. Author(s): Kaufman CL, Ildstad ST. Source: Neurochemical Research. 1999 April; 24(4): 537-49. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227686

•

Leukodystrophy and CSF purine abnormalities associated with isolated 3methylcrotonyl-CoA carboxylase deficiency. Author(s): de K, Latini A, Suormala T, Baumgartner ER, Larovere L, Civallero G, Guelbert N, Paschini-Capra A, Depetris-Boldini C, Mayor CQ. Source: Metabolic Brain Disease. 2002 March; 17(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893004

•

Leukodystrophy associated with oligodontia in a large inbred family: fortuitous association or new entity? Author(s): Atrouni S, Daraze A, Tamraz J, Cassia A, Caillaud C, Megarbane A. Source: American Journal of Medical Genetics. 2003 April 1; 118A(1): 76-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605447

•

Leukodystrophy in children: a pictorial review of MR imaging features. Author(s): Cheon JE, Kim IO, Hwang YS, Kim KJ, Wang KC, Cho BK, Chi JG, Kim CJ, Kim WS, Yeon KM. Source: Radiographics : a Review Publication of the Radiological Society of North America, Inc. 2002 May-June; 22(3): 461-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006681

Studies

47

•

Leukodystrophy in patients with ovarian dysgenesis. Author(s): Schiffmann R, Tedeschi G, Kinkel RP, Trapp BD, Frank JA, Kaneski CR, Brady RO, Barton NW, Nelson L, Yanovski JA. Source: Annals of Neurology. 1997 May; 41(5): 654-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9153528

•

Leukodystrophy incidence in Germany. Author(s): Heim P, Claussen M, Hoffmann B, Conzelmann E, Gartner J, Harzer K, Hunneman DH, Kohler W, Kurlemann G, Kohlschutter A. Source: American Journal of Medical Genetics. 1997 September 5; 71(4): 475-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9286459

•

Long tract degeneration in familial sudanophilic leukodystrophy with prominent spheroids. Author(s): Yazawa I, Nakano I, Yamada H, Oda M. Source: Journal of the Neurological Sciences. 1997 April 15; 147(2): 185-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9106126

•

Longitudinal neurophysiologic studies in a patient with metachromatic leukodystrophy following bone marrow transplantation. Author(s): Dhuna A, Toro C, Torres F, Kennedy WR, Krivit W. Source: Archives of Neurology. 1992 October; 49(10): 1088-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1417517

•

Long-term stabilization after bone marrow transplantation in juvenile metachromatic leukodystrophy. Author(s): Kidd D, Nelson J, Jones F, Dusoir H, Wallace I, McKinstry S, Patterson V. Source: Archives of Neurology. 1998 January; 55(1): 98-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443716

•

Low arylsulphatase A activity and choreoathetotic syndrome in three siblings: differentiation of pseudodeficiency from metachromatic leukodystrophy. Author(s): Kappler J, Watts RW, Conzelmann E, Gibbs DA, Propping P, Gieselmann V. Source: European Journal of Pediatrics. 1991 February; 150(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1674246

48

Leukodystrophy

•

Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy). Author(s): deGasperi R, Raghavan SS, Sosa MG, Kolodny EH, Carrier C, Rubenstein P, Peters C, Wagner J, Kurtzberg J, Krivit W. Source: Bone Marrow Transplantation. 2000 March; 25(5): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10713632

•

Megalencephaly and leukodystrophy with mild clinical course: a report on 12 new cases. Author(s): Topcu M, Saatci I, Topcuoglu MA, Kose G, Kunak B. Source: Brain & Development. 1998 April; 20(3): 142-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9628190

•

Metachromatic leukodystrophy and nonverbal learning disability: neuropsychological and neuroradiological findings in heterozygous carriers. Author(s): Weber Byars AM, McKellop JM, Gyato K, Sullivan T, Franz DN. Source: Neuropsychology, Development, and Cognition. Section C, Child Neuropsychology : a Journal on Normal and Abnormal Development in Childhood and Adolescence. 2001 March; 7(1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11815881

•

Metachromatic leukodystrophy in the Navajo: fallout of the American-Indian wars of the nineteenth century. Author(s): Holve S, Hu D, McCandless SE. Source: American Journal of Medical Genetics. 2001 July 1; 101(3): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11424134

•

Metachromatic leukodystrophy. Diffusion MR imaging and proton MR spectroscopy. Author(s): Sener RN. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2003 July; 44(4): 440-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846696

•

Metachromatic leukodystrophy: a model for the study of psychosis. Author(s): Black DN, Taber KH, Hurley RA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2003 Summer; 15(3): 289-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928504

Studies

49

•

Metachromatic leukodystrophy: a novel mutation (c237delC) and extension of the haplotype associated with the P426L mutation. Author(s): Gort L, Coll MJ, Chabas A. Source: Human Mutation. 2000 October; 16(4): 375-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11013459

•

Metachromatic leukodystrophy: diffusion MR imaging findings. Author(s): Sener RN. Source: Ajnr. American Journal of Neuroradiology. 2002 September; 23(8): 1424-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223391

•

Metachromatic leukodystrophy: molecular genetics and an animal model. Author(s): Gieselmann V, Matzner U, Hess B, Lullmann-Rauch R, Coenen R, Hartmann D, D'Hooge R, DeDeyn P, Nagels G. Source: Journal of Inherited Metabolic Disease. 1998 August; 21(5): 564-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9728336

•

Metachromatic leukodystrophy: recent research developments. Author(s): Gieselmann V. Source: Journal of Child Neurology. 2003 September; 18(9): 591-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572136

•

Metachromatic leukodystrophy: subtype genotype/phenotype correlations and identification of novel missense mutations (P148L and P191T) causing the juvenileonset disease. Author(s): Qu Y, Shapira E, Desnick RJ. Source: Molecular Genetics and Metabolism. 1999 July; 67(3): 206-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10381328

•

Molecular basis of late-life globoid cell leukodystrophy. Author(s): De Gasperi R, Gama Sosa MA, Sartorato E, Battistini S, Raghavan S, Kolodny EH. Source: Human Mutation. 1999; 14(3): 256-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10477434

•

Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation. Author(s): Gomez-Lira M, Perusi C, Mottes M, Pignatti PF, Manfredi M, Rizzuto N, Salviati A. Source: Human Genetics. 1998 April; 102(4): 459-63. Erratum In: Hum Genet 1998 May; 102(5): 602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600244

50

Leukodystrophy

•

Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Author(s): Wenger DA, Rafi MA, Luzi P. Source: Human Mutation. 1997; 10(4): 268-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9338580

•

Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships? Author(s): Baumann N, Turpin JC, Lefevre M, Colsch B. Source: Journal of Physiology, Paris. 2002 April-June; 96(3-4): 301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445909

•

MRI appearances of metachromatic leukodystrophy. Author(s): Faerber EN, Melvin J, Smergel EM. Source: Pediatric Radiology. 1999 September; 29(9): 669-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460327

•

Multifocal slowing of nerve conduction in metachromatic leukodystrophy. Author(s): Cameron CL, Kang PB, Burns TM, Darras BT, Jones HR Jr. Source: Muscle & Nerve. 2004 April; 29(4): 531-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052618

•

Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Author(s): Schuelke M, Smeitink J, Mariman E, Loeffen J, Plecko B, Trijbels F, StocklerIpsiroglu S, van den Heuvel L. Source: Nature Genetics. 1999 March; 21(3): 260-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10080174

•

Mutations associated with a childhood leukodystrophy, Alexander disease, cause deficiency in dimerization of the cytoskeletal protein GFAP. Author(s): Nielsen AL, Jorgensen P, Jorgensen AL. Source: Journal of Neurogenetics. 2002 July-September; 16(3): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12696672

•

Mutations associated with very late-onset metachromatic leukodystrophy. Author(s): Perusi C, Lira MG, Duyff RF, Weinstein HC, Pignatti PF, Rizzuto N, Salviati A. Source: Clinical Genetics. 1999 February; 55(2): 130. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10189092

Studies

51

•

N-acetylaspartic aciduria due to aspartoacylase deficiency--a new aetiology of childhood leukodystrophy. Author(s): Hagenfeldt L, Bollgren I, Venizelos N. Source: Journal of Inherited Metabolic Disease. 1987; 10(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3116332

•

N-acetylaspartic aciduria: report of three new cases in children with a neurological syndrome associating macrocephaly and leukodystrophy. Author(s): Divry P, Vianey-Liaud C, Gay C, Macabeo V, Rapin F, Echenne B. Source: Journal of Inherited Metabolic Disease. 1988; 11(3): 307-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3148075

•

Neuroaxonal leukodystrophy associated with congenital cutis laxa: report of an autopsy case. Author(s): Shintaku M, Uemura Y, Fujii I, Ohtani Y, Miike T, Tokunaga M, Tsubura A. Source: Acta Neuropathologica. 2000 April; 99(4): 420-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10787041

•

Neurochemical findings in a perinatal sudanophilic leukodystrophy rich in steryl ester. Author(s): Ramsey RB, Banik NL, Ramsey PT, Cuzner ML, Scott T, Dayan AD, Davison AN. Source: Journal of the Neurological Sciences. 1976 November; 30(1): 95-111. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=978227

•

Neurochemical findings in adreno-leukodystrophy. Author(s): Ramsey RB, Banik NL, Scott T, Davison AN. Source: Journal of the Neurological Sciences. 1976 October; 29(2-4): 277-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=185335

•

Neurological diseases as reflections of general metabolic disturbances (Wilson's disease, Refsum's disease and metachromatic leukodystrophy). Author(s): Cumings JN. Source: Int J Neurol. 1976; 11(1): 28-37. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=65341

•

Neuronal depletion of cerebellum in late infantile metachromatic leukodystrophy. Author(s): Yamano T, Ohta S, Shimada M, Okada S, Yutaka T, Sugita T, Yabuuchi H. Source: Brain & Development. 1980; 2(4): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7224092

52

Leukodystrophy

•

Neuropathological and enzymatic studies in a case of adult form of metachromatic leukodystrophy with very late onset of clinical symptoms. Author(s): Marmiroli P, Cavaletti G, Bertagnolio B, Maccarini B, Tredici G. Source: Acta Neurol (Napoli). 1990 June; 12(3): 184-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1976290

•

Neuropathy of metachromatic leukodystrophy: improvement with immunomodulation. Author(s): Nevo Y, Pestronk A, Lopate G, Carroll SL. Source: Pediatric Neurology. 1996 October; 15(3): 237-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8916163

•

Neurophysiological study in an Italian family with autosomal dominant late-onset leukodystrophy. Author(s): Leombruni S, Vaula G, Coletti Moja M, Bergui M, Bergamini L, Quattrocolo G. Source: Electromyogr Clin Neurophysiol. 1998 April-May; 38(3): 131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9637937

•

Neurophysiology and MRI in late-infantile metachromatic leukodystrophy. Author(s): Zafeiriou DI, Kontopoulos EE, Michelakakis HM, Anastasiou AL, Gombakis NP. Source: Pediatric Neurology. 1999 November; 21(5): 843-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10593679

•

Neuropsychological deficits in obligatory heterozygotes for metachromatic leukodystrophy. Author(s): Kohn H, Manowitz P, Miller M, Kling A. Source: Human Genetics. 1988 May; 79(1): 8-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3366464

•

New sites of ocular involvement in late-infantile metachromatic leukodystrophy revealed by histopathologic studies. Author(s): Scott IU, Green WR, Goyal AK, de la Cruz Z, Naidu S, Moser H. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1993 March; 231(3): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8462893

Studies

53

•

Non-membrane-bound cytoplasmic deposits in Krabbe globoid leukodystrophy: further evidence for a revised concept of lysosomal storage diseases. Author(s): Blinzinger K, Anzil AP. Source: Experientia. 1972 July 15; 28(7): 780-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4658853

•

Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophy. Author(s): Olkhovich NV, Takamura N, Pichkur NA, Gorovenko NG, Aoyagi K, Yamashita S. Source: Molecular Genetics and Metabolism. 2003 November; 80(3): 360-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14680985

•

Nuclear bodies in reactive astrocytes in two cases of leukodystrophy in monozygotic twins. Author(s): Predescu V, Alexianu M, Christodorescu D, Oancea C, Petrovici A. Source: Acta Neuropathologica. 1973; 25(3): 244-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4728560

•

Occurrence, distribution, and phenotype of arylsulfatase A mutations in patients with metachromatic leukodystrophy. Author(s): Berger J, Loschl B, Bernheimer H, Lugowska A, Tylki-Szymanska A, Gieselmann V, Molzer B. Source: American Journal of Medical Genetics. 1997 March 31; 69(3): 335-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9096767

•

Ocular features of multiple sulfatase deficiency and a new variant of metachromatic leukodystrophy. Author(s): Bateman JB, Philippart M, Isenberg SJ. Source: Journal of Pediatric Ophthalmology and Strabismus. 1984 July-August; 21(4): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6470909

•

Ocular findings in metachromatic leukodystrophy. An electron microscopic and enzyme study in different clinical and genetic variants. Author(s): Libert J, Van Hoof F, Toussaint D, Roozitalab H, Kenyon KR, Green WR. Source: Archives of Ophthalmology. 1979 August; 97(8): 1495-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=37822

54

Leukodystrophy

•

On a rare atypical form of metachromatic leukodystrophy (MLD): "neurological nonmld patients with low levels of arylsulphatase A". Description of two cases. Author(s): Grasso A, Fiumara A, Biondi R, Nigro F, Nardone G, Bonomo MG, Sicurella L, Scrofani A. Source: Acta Neurol (Napoli). 1989 August; 11(4): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2572149

•

On the dual nature and lack of specificity of intracytoplasmic inclusions in a case of adult onset orthochromatic leukodystrophy. Author(s): Sotrel A. Source: Journal of Neuropathology and Experimental Neurology. 1988 July; 47(4): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3385441

•

Optic nerve in globoid leukodystrophy (Krabbe's disease). Ultrastructural changes. Author(s): Brownstein S, Meagher-Villemure K, Polomeno RC, Little JM. Source: Archives of Ophthalmology. 1978 May; 96(5): 864-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=418756

•

Oral findings in metachromatic leukodystrophy. Author(s): Gardner DG, Zeman W. Source: Oral Surg Oral Med Oral Pathol. 1970 March; 29(3): 431-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5263274

•

Orthochromatic leukodystrophy with pigmented glial cells. An adult case with clinical-anatomical study. Author(s): Pietrini V, Tagliavini F, Pilleri G, Trabattoni CR, Lechi A. Source: Acta Neurologica Scandinavica. 1979 March; 59(2-3): 140-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=88156

•

Overexpression of arylsulfatase A gene in fibroblasts from metachromatic leukodystrophy patients does not induce a new phenotype. Author(s): Ohashi T, Matalon R, Barranger JA, Eto Y. Source: Gene Therapy. 1995 August; 2(6): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7584110

•

Papillomatosis of the gallbladder in metachromatic leukodystrophy. Author(s): Oak S, Rao S, Karmarkar S, Kulkarni B, Kalgutkar A, Malde A, Naik L. Source: Pediatric Surgery International. 1997 July; 12(5-6): 424-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9244117

Studies

55

•

Papillomatous transformation of the gallbladder in metachromatic leukodystrophy. Author(s): Tesluk H, Munn RJ, Schwartz MZ, Ruebner BH. Source: Pediatr Pathol. 1989; 9(6): 741-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2690041

•

Partial seizures in two cases of metachromatic leukodystrophy: electrophysiologic and neuroradiologic findings. Author(s): Fukumizu M, Matsui K, Hanaoka S, Sakuragawa N, Kurokawa T. Source: Journal of Child Neurology. 1992 October; 7(4): 381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1281851

•

Pathological case of the month. Globoid cell leukodystrophy (Krabbe's disease). Author(s): Rueca RE, Taxy JB, Wollmann RL. Source: Archives of Pediatrics & Adolescent Medicine. 1995 October; 149(10): 1173-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7550826

•

Pigmentary type of orthochromatic leukodystrophy (OLD): a new case with ultrastructural and biochemical study. Author(s): Gray F, Destee A, Bourre JM, Gherardi R, Krivosic I, Warot P, Poirier J. Source: Journal of Neuropathology and Experimental Neurology. 1987 September; 46(5): 585-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3625235

•

Pigmentary type of orthochromatic leukodystrophy with early onset and protracted course. Author(s): Seiser A, Jellinger K, Brainin M. Source: Neuropediatrics. 1990 February; 21(1): 48-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2314558

•

Polyposis of the gallbladder associated with metachromatic leukodystrophy. Author(s): Ries M, Deeg KH. Source: European Journal of Pediatrics. 1993 May; 152(5): 450-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8319717

•

Potential environmental and host participants in the early white matter lesion of adreno-leukodystrophy: morphologic evidence for CD8 cytotoxic T cells, cytolysis of oligodendrocytes, and CD1-mediated lipid antigen presentation. Author(s): Ito M, Blumberg BM, Mock DJ, Goodman AD, Moser AB, Moser HW, Smith KD, Powers JM. Source: Journal of Neuropathology and Experimental Neurology. 2001 October; 60(10): 1004-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11589421

56

Leukodystrophy

•

Practical suggestions in diagnosing metachromatic leukodystrophy in probands and in testing family members. Author(s): Tylki-Szymanska AT, Czartoryska B, Lugowska A. Source: European Neurology. 1998 August; 40(2): 67-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9693234

•

Prenatal enzymatic diagnosis and exclusion of Krabbe's disease (globoid-cell leukodystrophy) using chorionic villi in five risk pregnancies. Author(s): Harzer K, Hager HD, Tariverdian G. Source: Human Genetics. 1987 December; 77(4): 342-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3692478

•

Prenatal enzymatic diagnosis of Krabbe disease (globoid-cell leukodystrophy) using chorionic villi. Pitfalls in the use of uncultured villi. Author(s): Harzer K, Schuster I. Source: Human Genetics. 1989 December; 84(1): 83-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2606482

•

Presymptomatic late-infantile metachromatic leukodystrophy treated with bone marrow transplantation. Author(s): Pridjian G, Humbert J, Willis J, Shapira E. Source: The Journal of Pediatrics. 1994 November; 125(5 Pt 1): 755-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7965430

•

Prevalence of arylsulfatase A pseudodeficiency allele in metachromatic leukodystrophy patients from Poland. Author(s): Lugowska A, Czartoryska B, Tylki-Szymanska A, Bisko M, Zimowski JG, Berger J, Molzer B. Source: European Neurology. 2000; 44(2): 104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10965162

•

Prevalence of arylsulphatase A mutations in 11 Japanese patients with metachromatic leukodystrophy: identification of two novel mutations. Author(s): Kurosawa K, Ida H, Eto Y. Source: Journal of Inherited Metabolic Disease. 1998 October; 21(7): 781-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9819708

•

Prevalence of common mutations in the arylsulphatase A gene in metachromatic leukodystrophy patients diagnosed in Britain. Author(s): Barth ML, Fensom A, Harris A. Source: Human Genetics. 1993 March; 91(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8095918

Studies

57

•

Prevention of deterioration in metachromatic leukodystrophy by bone marrow transplantation. Author(s): Krivit W, Lipton ME, Lockman LA, Tsai M, Dyck PJ, Smith S, Ramsay NK, Kersey J. Source: The American Journal of the Medical Sciences. 1987 August; 294(2): 80-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3307409

•

Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology. Author(s): Hohenschutz C, Friedl W, Schlor KH, Waheed A, Conzelmann E, Sandhoff K, Propping P. Source: American Journal of Medical Genetics. 1988 September; 31(1): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2906225

•

Progressive familial leukodystrophy of late onset. Author(s): Knopman D, Sung JH, Davis D. Source: Neurology. 1996 February; 46(2): 429-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8614507

•

Psychiatric disturbances in metachromatic leukodystrophy. Insights into the neurobiology of psychosis. Author(s): Hyde TM, Ziegler JC, Weinberger DR. Source: Archives of Neurology. 1992 April; 49(4): 401-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532712

•

Psychopathology in metachromatic leukodystrophy. Author(s): Merriam AE, Hegarty AM. Source: Archives of Neurology. 1993 February; 50(2): 131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8431128

•

Qualitative and quantitative differences in sulfatase A which distinguish different forms of classical metachromatic leukodystrophy (MLD). Author(s): Stumpf D, Austin J. Source: Journal of Neuropathology and Experimental Neurology. 1971 January; 30(1): 147. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5100707

•

Qualitative and quantitative differences in sulfatase A which distinguish the different forms of classical metachromatic leukodystrophy (MLD). Author(s): Stumpf D, Austin JH. Source: Trans Am Neurol Assoc. 1970; 95: 315-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5514400

58

Leukodystrophy

•

Rapid detection of common metachromatic leukodystrophy mutations by restriction analysis of arylsulfatase A gene amplimers. Author(s): Ben-Yoseph Y, Mitchell DA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1994 April; 226(1): 77-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7915220

•

Rapid detection of common mutation of arylsulfatase A in metachromatic leukodystrophy by polymerase chain reaction with a mismatched primer. Author(s): Ohshima T, Sasaki M, Takahashi J, Sakuragawa N. Source: Journal of Child Neurology. 1994 January; 9(1): 38-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7908679

•

Re.: Clinical, radiological and pathological findings in an autosomal dominant leukodystrophy. Author(s): Koeppen AH. Source: Journal of the Neurological Sciences. 2001 June 15; 187(1-2): 107, 109. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486760

•

Recurrent seizures in metachromatic leukodystrophy. Author(s): Balslev T, Cortez MA, Blaser SI, Haslam RH. Source: Pediatric Neurology. 1997 September; 17(2): 150-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9367296

•

Renal cerebroside in globoid cell leukodystrophy (Krabbe's disease). Author(s): Suzuki K. Source: Lipids. 1971 June; 6(6): 433-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5117254

•

Repeated upper gastrointestinal hemorrhage caused by metachromatic leukodystrophy of the gall bladder. Author(s): Siegel EG, Lucke H, Schauer W, Creutzfeldt W. Source: Digestion. 1992; 51(2): 121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499874

•

Report on a patient with congenital muscular dystrophy, hydrocephalus, DandyWalker malformation and leukodystrophy. Author(s): Di Rocco M, Leveratto L, Cama A, Bado M, Tortori Donati P, Andreussi L, Borrone C. Source: Genet Couns. 1993; 4(4): 295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8110418

Studies

59

•

Research update on lysosomal disorders with special emphasis on metachromatic leukodystrophy and Krabbe disease. Author(s): Wenger DA. Source: Apmis. Supplementum. 1993; 40: 81-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8311994

•

Riboflavin-responsive glutaric aciduria type II presenting as a leukodystrophy. Author(s): Uziel G, Garavaglia B, Ciceri E, Moroni I, Rimoldi M. Source: Pediatric Neurology. 1995 November; 13(4): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8771170

•

Seizures as a presenting feature of late onset metachromatic leukodystrophy. Author(s): Bostantjopoulou S, Katsarou Z, Michelakaki H, Kazis A. Source: Acta Neurologica Scandinavica. 2000 September; 102(3): 192-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987380

•

Serial magnetic resonance imaging studies in a case of late onset globoid cell leukodystrophy. Author(s): Tada K, Taniike M, Ono J, Tsukamoto H, Inui K, Okada S. Source: Neuropediatrics. 1992 December; 23(6): 306-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1491749

•

Serial MR after bone marrow transplantation in two patients with metachromatic leukodystrophy. Author(s): Stillman AE, Krivit W, Shapiro E, Lockman L, Latchaw RE. Source: Ajnr. American Journal of Neuroradiology. 1994 November; 15(10): 1929-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7863944

•

Siblings with the Austin variant of metachromatic leukodystrophy multiple sulfatidosis. Author(s): Bharucha BA, Naik G, Savliwala AS, Joshi RM, Kumta NB. Source: Indian J Pediatr. 1984 July-August; 51(411): 477-80. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6441775

•

Simultaneous detection of the two most frequent metachromatic leukodystrophy mutations. Author(s): Berger J, Molzer B, Gieselmann V, Bernheimer H. Source: Human Genetics. 1993 October; 92(4): 421-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7901143

60

Leukodystrophy

•

Slow progression of juvenile metachromatic leukodystrophy 6 years after bone marrow transplantation. Author(s): Kapaun P, Dittmann RW, Granitzny B, Eickhoff W, Wulbrand H, NeumaierProbst E, Zander A, Kohlschuetter A. Source: Journal of Child Neurology. 1999 April; 14(4): 222-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10334395

•

Studies in metachromatic leukodystrophy. XIV. Purification and subunit structure of human liver arylsulfatase A. Author(s): James GT, Austin JH. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1979 October 15; 98(1-2): 103-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=40716

•

Successful paroxetine treatment of major depression in an adult form of metachromatic leukodystrophy with cognitive disturbances. Author(s): Vella G, Loriedo C, Raccah R, Baldassarre P, Paolillo A. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 September; 43(7): 748-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773228

•

Successful transduction of oligodendrocytes and restoration of arylsulfatase A deficiency in metachromatic leukodystrophy fibroblasts using an adenovirus vector. Author(s): Ohashi T, Watabe K, Sato Y, Saito I, Barranger JA, Eto Y. Source: Gene Therapy. 1995 September; 2(7): 443-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7584122

•

Sulfatides in prenatal metachromatic leukodystrophy. Author(s): Baier W, Harzer K. Source: Journal of Neurochemistry. 1983 December; 41(6): 1766-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6644310

•

Symptomatology of late onset Krabbe's leukodystrophy: the European experience. Author(s): Lyon G, Hagberg B, Evrard P, Allaire C, Pavone L, Vanier M. Source: Developmental Neuroscience. 1991; 13(4-5): 240-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1817027

•

Thalamic and basal ganglia hyperdensities--a CT marker for globoid cell leukodystrophy? Author(s): Jardim LB, Giugliani R, Fensom AH. Source: Neuropediatrics. 1992 February; 23(1): 30-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1565214

Studies

61

•

The differential diagnosis of adult onset metachromatic leukodystrophy and early onset familial Alzheimer disease in an Alzheimer clinic population. Author(s): Sadovnick AD, Tuokko H, Applegarth DA, Toone JR, Hadjistavropoulos T, Beattie BL. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1993 November; 20(4): 312-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8313247

•

The future for treatment by bone marrow transplantation for adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome. Author(s): Krivit W, Lockman LA, Watkins PA, Hirsch J, Shapiro EG. Source: Journal of Inherited Metabolic Disease. 1995; 18(4): 398-412. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7494399

•

The inflammatory myelinopathy of adreno-leukodystrophy: cells, effector molecules, and pathogenetic implications. Author(s): Powers JM, Liu Y, Moser AB, Moser HW. Source: Journal of Neuropathology and Experimental Neurology. 1992 November; 51(6): 630-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1362438

•

The mechanism for a 33-nucleotide insertion in mRNA causing sphingolipid activator protein (SAP-1)-deficient metachromatic leukodystrophy. Author(s): Zhang XL, Rafi MA, DeGala G, Wenger DA. Source: Human Genetics. 1991 June; 87(2): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2066109

•

The R496H mutation of arylsulfatase A does not cause metachromatic leukodystrophy. Author(s): Ricketts MH, Poretz RD, Manowitz P. Source: Human Mutation. 1998; 12(4): 238-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744473

•

Transduced fibroblasts and metachromatic leukodystrophy lymphocytes transfer arylsulfatase A to myelinating glia and deficient cells in vitro. Author(s): Sangalli A, Taveggia C, Salviati A, Wrabetz L, Bordignon C, Severini GM. Source: Human Gene Therapy. 1998 September 20; 9(14): 2111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9759937

62

Leukodystrophy

•

Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patient. Author(s): Fluharty AL, Fluharty CB, Bohne W, von Figura K, Gieselmann V. Source: American Journal of Human Genetics. 1991 December; 49(6): 1340-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1684088

•

Two new polymorphisms in the arylsulfatase A gene and their haplotype associations with normal, metachromatic leukodystrophy and pseudodeficiency alleles. Author(s): Coulter-Mackie M, Gagnier L. Source: American Journal of Medical Genetics. 1997 November 28; 73(1): 32-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9375919

•

Two novel mutations in the arylsulfatase A gene associated with juvenile (R390Q) and adult onset (H397Y) metachromatic leukodystrophy. Author(s): Coulter-Mackie MB, Gagnier L. Source: Human Mutation. 1998; Suppl 1: S254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452102

•

Ultrastructural findings of peripheral nerve in a case of juvenile atypical metachromatic leukodystrophy. Author(s): Di Trapani G, Pocchiari M, Pinto F. Source: Acta Neurol (Napoli). 1979 October; 1(5): 371-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=229702

•

Ultrastructural findings of peripheral nerve in a preclinical case of adult metachromatic leukodystrophy. Author(s): Argyrakis A, Pilz H, Goebel HH, Muller D. Source: Journal of Neuropathology and Experimental Neurology. 1977 July; 36(4): 693711. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=196053

•

Ultrastructural pathology of eccrine sweat gland epithelial cells in globoid cell leukodystrophy. Author(s): Goebel HH, Kimura S, Harzer K, Klein H. Source: Journal of Child Neurology. 1993 April; 8(2): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8389389

•

Ultrastructural study of neurons in metachromatic leukodystrophy. Author(s): Peng L, Suzuki K. Source: Clin Neuropathol. 1987 September-October; 6(5): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2826059

Studies

63

•

Ultrastructural study of the retina in late infantile metachromatic leukodystrophy. Author(s): Goebel HH, Busch-Hettwer H, Bohl J. Source: Ophthalmic Research. 1992; 24(2): 103-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1608595

•

Ultrastructure of central nervous system lesions in metachromatic leukodystrophy with special reference to morphogenesis. Author(s): Liu HM. Source: Journal of Neuropathology and Experimental Neurology. 1968 October; 27(4): 624-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5303218

•

Ultrastructure of globoid leukodystrophy (Krabbe's disease) with reference to the origin of globoid cells. Author(s): Liu HM. Source: Journal of Neuropathology and Experimental Neurology. 1970 July; 29(3): 44162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5433207

•

Unusual gallbladder findings in two brothers with metachromatic leukodystrophy. Author(s): Simanovsky N, Ackerman Z, Kiderman A, Fields S. Source: Pediatric Radiology. 1998 September; 28(9): 706-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9732500

•

Unusual orthochromatic leukodystrophy with epitheloid cells (Norman-Gullotta): increase of very long chain fatty acids in brain discloses a peroxisomal disorder. Author(s): Molzer B, Gullotta F, Harzer K, Poulos A, Bernheimer H. Source: Acta Neuropathologica. 1993; 86(2): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8213073

•

Urine sulfatides and the diagnosis of metachromatic leukodystrophy. Author(s): Natowicz MR, Prence EM, Chaturvedi P, Newburg DS. Source: Clinical Chemistry. 1996 February; 42(2): 232-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8595716

•

Variable onset of metachromatic leukodystrophy in a Vietnamese family. Author(s): Arbour LT, Silver K, Hechtman P, Treacy EP, Coulter-Mackie MB. Source: Pediatric Neurology. 2000 August; 23(2): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020646

64

Leukodystrophy

•

Very low arylsulfatase A and cerebroside sulfatase activities in leukocytes of healthy members of metachromatic leukodystrophy family. Author(s): Dubois G, Harzer K, Baumann N. Source: American Journal of Human Genetics. 1977 March; 29(2): 191-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15452

•

Villous papilloma of the gallbladder in association with leukodystrophy. Author(s): Warfel KA, Hull MT. Source: Human Pathology. 1984 December; 15(12): 1192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6500553

•

White matter changes mimicking a leukodystrophy in a patient with Mucopolysaccharidosis: characterization by MRI. Author(s): Barone R, Parano E, Trifiletti RR, Fiumara A, Pavone P. Source: Journal of the Neurological Sciences. 2002 March 30; 195(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897250

65

CHAPTER 2. NUTRITION AND LEUKODYSTROPHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and leukodystrophy.

Finding Nutrition Studies on Leukodystrophy The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “leukodystrophy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

66

Leukodystrophy

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

Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo. Author(s): Universitatskinderklinik, Schwerpunkt Neuropadiatrie, Gottingen, Germany. Source: Kruse, B Hanefeld, F Christen, H J Bruhn, H Michaelis, T Hanicke, W Frahm, J JNeurol. 1993 December; 241(2): 68-74 0340-5354

•

Galactosylceramide lipidosis: globoid cell leukodystrophy (Krabbe's disease). Source: Suzuki, K. Suzuki, Y. The Metabolic basis of inherited disease / [edited by] John B. Stanbury. [et al.]. 5th ed. New York : McGraw-Hill, 1983. page 857-880. ill. ISBN: 0070607265

•

L-cycloserine slows the clinical and pathological course in mice with globoid cell leukodystrophy (twitcher mice). Author(s): Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, USA. [email protected] Source: LeVine, S M Pedchenko, T V Bronshteyn, I G Pinson, D M J-Neurosci-Res. 2000 April 15; 60(2): 231-6 0360-4012

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Nutrition

67

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

69

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

Auditory brainstem responses (ABR) in children with neurological disorders. Author(s): el Khateeb I, Abdul Razzak B, Moosa A. Source: Brain & Development. 1988; 10(4): 243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3218703

•

Brain stem auditory, visual and somatosensory evoked potentials in leukodystrophies. Author(s): Markand ON, Garg BP, DeMyer WE, Warren C, Worth RM. Source: Electroencephalography and Clinical Neurophysiology. 1982 July; 54(1): 39-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6177516

70

Leukodystrophy

•

Enzyme replacement with liposomes containing beta-galactosidase from Charonia lumpas in murine globoid cell leukodystrophy (twitcher). Author(s): Umezawa F, Eto Y, Tokoro T, Ito F, Maekawa K. Source: Biochemical and Biophysical Research Communications. 1985 March 15; 127(2): 663-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3919736

•

Leukocyte sonicates as a source for both enzyme assay and DNA amplification for mutational analysis of certain lysosomal disorders. Author(s): Louie E, Rafi MA, Wenger DA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1991 May 31; 199(1): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682071

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

•

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/

Alternative Medicine 71

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

Herbs and Supplements Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com

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.

73

CHAPTER 4. PATENTS ON LEUKODYSTROPHY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “leukodystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on leukodystrophy, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Leukodystrophy By performing a patent search focusing on leukodystrophy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

74

Leukodystrophy

example of the type of information that you can expect to obtain from a patent search on leukodystrophy: •

Aspartoacylase gene, protein, and methods of screening for mutatons associated with canavan disease Inventor(s): Balamurugan; Kuppareddi (Miami, FL), Gao; Guang Ping (Miami, FL), Kaul; Rajinder (Miami, FL), Matalon; Reuben (Coral Gables, FL), Michals-Matalon; Kimberlee (Coral Gables, FL) Assignee(s): Miami Children's Hospital Research Institute, Inc. (Miami, FL) Patent Number: 5,679,635 Date filed: September 9, 1994 Abstract: Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. Human aspartoacylase (ASP) cDNA spanning 1,435 bp has been cloned and expressed in E. coli. A base change, a854>c, has been found in 85% of the 34 Canavan alleles tested so far, which results in a missense glu285>ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. Several additional mutations have also been identified. The invention therefore provides nucleic acid sequences, genes, polypeptides, antibodies, vectors containing the gene, host cells transformed with vectors containing the gene, animal models for the disease, methods for expressing the polypeptide, genetic screening methods and kits, diagnostic methods and kits, methods of treating Canavan disease and methods of genetic therapy for the disease. Excerpt(s): Canavan disease (CD), or spongy degeneration of brain, is an autosomal recessive leukodystrophy associated with mental retardation, megalencephaly, hypotonia and death, usually in the first decade of life. Brain histology in CD is characterized by spongy degeneration of white matter with astrocytic swelling and elongated mitochondria.sup.1-5. Canavan disease is more prevalent in Jewish people of Ashkenazi origin.sup.3-5. Matalon et al. (1988) described aspartoacylase deficiency as the basic biochemical defect in CD.sup.6. Since the initial report, 145 patients have been diagnosed with CD at a single center, suggesting that CD is more prevalent than previously thought.sup.10-12. Aspartoacylase deficiency in CD has also been reported by other investigators.sup.13,14. The deficiency of aspartoacylase in CD leads to excessive excretion of NAA in urine and its accumulation in brain.sup.6,9-11. Aspartoacylase in brain has been localized to white matter associated with myelin tracks.sup.16. How aspartoacylase and the hydrolysis of NAA are involved in keeping white matter intact is not clear. It is also not understood how the deficiency of aspartoacylase leads to the pathogenesis seen in CD. Aspartoacylase has been purified and characterized from bovine brain and from other bovine and human sources.sup.16. Biochemical and immunochemical studies suggest that aspartoacylase has been conserved during evolution. Aspartoacylase activity has been found in a variety of mammalian tissues, including kidney, brain white matter, adrenal glands, lung, liver and cultured skin fibroblasts. Brain grey matter and blood constituents do not have any detectable aspartoacylase activity (Kaul et al., unpublished studies). Web site: http://www.delphion.com/details?pn=US05679635__

Patents 75

•

Marker for individuals susceptible to alcoholism Inventor(s): Manowitz; Paul (East Brunswick, NJ), Park; David (New York, NY), Poretz; Ronald D. (Marlboro, NJ), Ricketts; Michael (Somerset, NJ) Assignee(s): Algene LLC (East Brunswick, NJ) Patent Number: 5,736,325 Date filed: August 31, 1994 Abstract: The present invention relates to methods for diagnosis of susceptibility to alcoholism or the pathological effects of alcoholism based on detection of a genetic marker in an individual. The present invention is directed generally to methods and associated compositions and kits for detecting the presence of arylsulfatase A (ASA) pseudodeficiency (PD) mutations in humans. Detection of these mutations has been surprisingly found to be a strong indicator for susceptibility to alcoholism and/or susceptibility to alcohol's pathological effects, as well as an important marker in evaluating the likelihood of metachromatic leukodystrophy (MLD). Excerpt(s): The present invention relates to methods for diagnosis of susceptibility to alcoholism or the pathological effects of alcoholism based on detection of a genetic marker in an individual. A large number of adoption and twin studies indicate that there is a genetic factor or factors to at least some forms of alcoholism (Goodwin, 1979, Arch. Gen. Psychiatry 36:57-61). However, to date, the only genetic factor that has been clearly identified in alcoholism is a deficiency in aldehyde dehydrogenase activity. This deficiency leads to a reduction, not an increase, in the rate of alcoholism. Earlier studies showed that arylsulfatase A (ASA) electrophoresed in native polyacrylamide gels and stained for enzymatic activity exhibited a variety of electrophoretic patterns, some of which were more likely to be found in alcoholic patients than in non-alcoholic psychiatric and normal control subjects (Hulyalkar et al., 1984, Alcoh.: Clin. Exp. Res. 8:337-341). However, lacking any biochemical explanation for these observations, no correlation with a genetic basis or marker for alcoholism was possible. Web site: http://www.delphion.com/details?pn=US05736325__

Patent Applications on Leukodystrophy As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to leukodystrophy:

9

This has been a common practice outside the United States prior to December 2000.

76

•

Leukodystrophy

Aspartoacylase gene, protein, and methods of screening for mutations associated with Canavan disease Inventor(s): Balamurugan, Kuppareddi; (Miami, FL), Cao, Guang Ping; (Miami, FL), Kaul, Rajinder; (Miami, FL), Matalon, Reuben; (Coral Gables, FL), Michals-Matalon, Kimberlee; (Coral Gables, FL) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030017473 Date filed: October 1, 2001 Abstract: Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency of aspartoacylase and accumulation of N-acetylaspartic acid in brain. Human aspartoacylase (ASP) cDNA spanning 1,435 bp has been cloned and expressed in E. coli. A base change, a854>c, has been found in 85% of the 34 Canavan alleles tested so far, which results in a missense glu285>ala mutation that is predicted to be part of the catalytic domain of aspartoacylase. The invention therefore provides nucleic acid sequences, genes, polypeptides, antibodies, vectors containing the gene, host cells transformed with vectors containing the gene, animal models for the disease, methods for expressing the polypeptide, genetic screening methods and kits, diagnostic methods and kits, methods of treating Canavan disease and methods of genetic therapy for the disease. Excerpt(s): Canavan disease (CD), or spongy degeneration of brain, is an autosomal recessive leukodystrophy associated with mental retardation, megalencephaly, hypotonia and death, usually in the first decade of life. Brain histology in CD is characterized by spongy degeneration of white matter with astrocytic swelling and elongated mitochondria.sup.1-5. Canavan disease is more prevalent in Jewish people of Ashkenazi origin.sup.3-5. Matalon et al. (1988) described aspartoacylase deficiency as the basic biochemical defect in CD.sup.6. Since the initial report, 145 patients have been diagnosed with CD a single center, suggesting that CD is more prevalent than previously thought.sup.10-12. Aspartoacylase deficiency in CD has also been reported by other investigators.sup.13,14. The deficiency of aspartoacylase in CD leads to excessive excretion of NAA in urine and its accumulation in brain.sup.6,9-11. Aspartoacylase in brain has been localized to white matter associated with myelin tracks.sup.16. How aspartoacylase and the hydrolysis of NAA are involved in keeping white matter intact is not clear. It is also not understood how the deficiency of aspartoacylase leads to the pathogenesis seen in CD. Aspartoacylase has been purified and characterized from bovine brain and from other bovine and human sources.sup.16. Biochemical and immunochemical studies suggest that aspartoacylase has been conserved during evolution. Aspartoacylase activity has been found in a variety of mammalian tissues, including kidney, brain white matter, adrenal glands, lung, liver and cultured skin fibroblasts. Brain grey matter and blood constituents do not have any detectable aspartoacylase activity (Kaul et al., unpublished studies). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 77

Keeping Current In order to stay informed about patents and patent applications dealing with leukodystrophy, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “leukodystrophy” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on leukodystrophy. You can also use this procedure to view pending patent applications concerning leukodystrophy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

79

APPENDICES

81

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 Institute10: •

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/

10

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

82

Leukodystrophy

•

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

83

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 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:12 •

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

11

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

84

Leukodystrophy

•

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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “leukodystrophy” (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 1973 4 24 0 60 2061

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “leukodystrophy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

85

Coffee Break: Tutorials for Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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.

87

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 leukodystrophy 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 leukodystrophy. 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 leukodystrophy. 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 “leukodystrophy”:

88

Leukodystrophy

Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.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: •

Leukodystrophy Summary: A general overview of leukodystrophy that includes a description of the disorder, and treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2237 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 leukodystrophy. 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.

Patient Resources

89

NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on leukodystrophy can be purchased from NORD for a nominal fee. 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 Leukodystrophy The following is a list of associations that provide information on and resources relating to leukodystrophy: •

United Leukodystrophy Foundation Telephone: (815) 895-3211 Toll-free: (800) 728-5483 Fax: (815) 895-2432 Email: [email protected] Web Site: http://www.ulf.org/ Background: The United Leukodystrophy Foundation (ULF) is a voluntary not-forprofit organization dedicated to helping children and adults with leukodystrophy and assisting the family members, caregivers, and professionals who serve them. Leukodystrophy is a group of rare, progressive diseases that affect the white matter of the brain. Established in 1982, the United Leukodystrophy Foundation is committed to the identification, treatment, and cure of all leukodystrophies through programs of education, advocacy, research, and service. The Foundation also provides appropriate referrals, including to support groups; promotes professional and patient education; and offers a variety of educational and support materials. These include a regular newsletter, brochures, and audiovisual aids. Relevant area(s) of interest: Leukodystrophy

90

Leukodystrophy

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

Patient Resources

91

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

93

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.21

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

21

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

94

Leukodystrophy

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)22: •

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/

22

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

Finding Medical Libraries

95

•

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/

96

Leukodystrophy

•

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

97

•

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/

98

Leukodystrophy

•

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

99

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

101

LEUKODYSTROPHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] AdrenoAerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aetiology: Study of the causes of disease. [EU] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the

102

Leukodystrophy

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] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

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]

Dictionary 103

Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] 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] Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]

104

Leukodystrophy

Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH]

Dictionary 105

Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

106

Leukodystrophy

Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] 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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates

Dictionary 107

are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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 Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell 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] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU]

108

Leukodystrophy

Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] 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] Cholecystitis: Inflammation of the gallbladder. [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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chorionic Villi: The threadlike, vascular projections of the chorion which enter into the formation of the placenta. [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] Chronic Disease: Disease or ailment of long duration. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] 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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but

Dictionary 109

some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [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

110

Leukodystrophy

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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH]

Dictionary 111

Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] 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] Cytochrome-c Oxidase: An enzyme complex of the inner mitochondrial membrane that catalyzes the reaction between ferrocytochrome c and oxygen to yield ferricytochrome c and water. It is associated with the pumping of protons and the resultant phosphorylation of ADP to ATP. The reaction is the terminal event in the electron transport scheme by which oxygen is used for fuel combustion. EC 1.9.3.1. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] 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] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH]

112

Leukodystrophy

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] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Duct: A tube through which body fluids pass. [NIH] Dysgenesis: Defective development. [EU] Dysostosis: Defective bone formation. [NIH]

Dictionary 113

Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] 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] 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

114

Leukodystrophy

uniform in size and stainable by eosin. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filariasis: Infections with nematodes of the superfamily Filarioidea. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischaemic necrosis of the brain, blindness, and dermatosis of the face. [NIH]

Dictionary 115

Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Galactosylceramidase: An enzyme that hydrolyzes galactose from ceramide monohexosides. Deficiency of this enzyme may cause globoid cell leukodystrophy. EC 3.2.1.46. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [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 Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug

116

Leukodystrophy

sensitivity, particularly for leukemia. [NIH] Genes, pol: DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to

Dictionary 117

replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH]

118

Leukodystrophy

Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Iduronidase: An enzyme that hydrolyzes iduronosidic linkages in desulfated dermatan. Deficiency of this enzyme produces Hurler's syndrome. EC 3.2.1.76. [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] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Individuality: Those psychological characteristics which differentiate individuals from one another. [NIH]

Dictionary 119

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

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH] Intermediate Filament Proteins: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin,

120

Leukodystrophy

decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] 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] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Karyotypes: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU]

Dictionary 121

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] 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] Localized: Cancer which has not metastasized yet. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down

122

Leukodystrophy

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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannosidosis: Inborn error of metabolism marked by a defect in alpha-mannosidase activity that results in lysosomal accumulation of mannose-rich substrates. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megalencephaly: A condition in which there is an abnormally large, heavy, and usually malfunctioning brain. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] 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

Dictionary 123

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 Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] 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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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

124

Leukodystrophy

of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutism: Inability or refusal to speak. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelin Proteins: Proteins found in the myelin sheath. The major proteins of central nervous system myelin include: myelin proteolipid protein, myelin basic proteins, and myelinassociated glycoprotein. The major proteins of peripheral nervous system myelin include: myelin basic proteins (myelin p1 protein and myelin p2 protein), myelin p0 protein, and myelin-associated glycoprotein. [NIH] Myelin Sheath: The lipid-rich sheath investing many axons in both the central and peripheral nervous systems. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (Schwann cells in the peripheral and oligodendroglia in the central nervous system). Deterioration of the sheath in demyelinating diseases is a serious clinical problem. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH]

Dictionary 125

Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized 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] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [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] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular

126

Leukodystrophy

endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] 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] Oligodendroglia: A class of neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal satellite cells according to their location. The most important recognized function of these cells is the formation of the insulating myelin sheaths of axons in the central nervous system. [NIH] Oligodendroglial: A cell that lays down myelin. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

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] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation)

Dictionary 127

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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH]

128

Leukodystrophy

Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH]

Dictionary 129

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] 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]

130

Leukodystrophy

Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosine: An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged

Dictionary 131

psychotic. [EU] Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [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]

Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recessive gene: A gene that is phenotypically expressed only when homozygous. [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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]

132

Leukodystrophy

Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] 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 Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH]

Dictionary 133

Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol

134

Leukodystrophy

Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the

Dictionary 135

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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH]

136

Leukodystrophy

Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] 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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [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]

Dictionary 137

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] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and

138

Leukodystrophy

constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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]

Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [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] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and

Dictionary 139

kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] 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] Vivo: Outside of or removed from the body of a living organism. [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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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]

141

INDEX A Abdomen, 101, 106, 121, 127, 132, 134, 135, 139 Ablation, 13, 101 Acetylcholine, 101, 125, 126 Actin, 17, 101, 123 Adaptability, 101, 107 Adaptation, 11, 101 Adenovirus, 60, 101 Adjustment, 101 Adrenal Glands, 74, 76, 101 Adrenal insufficiency, 30, 101 Adrenoleukodystrophy, 24, 61 Aerobic, 14, 101, 123, 127 Aerobic Metabolism, 14, 101, 127 Aerobic Respiration, 101, 127 Aetiology, 51, 101 Affinity, 101, 104, 134 Aldehyde Dehydrogenase, 75, 102 Algorithms, 5, 102, 105 Alkaline, 102, 106, 127 Alleles, 27, 62, 74, 76, 102, 117 Allogeneic, 22, 102, 117 Alpha-1, 102, 128 Alternative medicine, 102 Amino acid, 4, 17, 22, 102, 103, 108, 111, 116, 126, 127, 129, 130, 132, 133, 135, 137 Amino Acid Sequence, 4, 102, 103, 116 Amino Acid Substitution, 4, 102 Ammonia, 102, 135, 137 Amplification, 70, 102 Amygdala, 102, 105, 136 Anaesthesia, 22, 102, 119 Anal, 15, 103 Analogous, 103, 137 Anatomical, 54, 103, 108, 118, 123, 133 Anemia, 103, 122 Animal model, 4, 13, 14, 15, 49, 74, 76, 103 Annealing, 103, 129 Anomalies, 5, 103 Antibiotic, 18, 103, 111 Antibodies, 16, 74, 76, 103, 121, 128 Antibody, 102, 103, 109, 117, 119, 134 Anticoagulant, 103, 130 Antigen, 101, 103, 109, 117, 119, 123 Antioxidants, 10, 103 Anus, 103, 120 Apoptosis, 9, 103

Arginine, 103, 125 Arteries, 103, 105, 106, 110, 121, 123, 137 Artery, 103, 105, 110, 133, 137 Assay, 70, 104 Astrocytes, 4, 6, 7, 16, 18, 53, 104, 123 Asymptomatic, 104, 114 Ataxia, 6, 20, 22, 23, 25, 104, 118, 136 Atrophy, 29, 104, 125 Attenuated, 104, 138 Atypical, 6, 42, 54, 62, 104 Audiovisual Aids, 89, 104 Auditory, 69, 104, 114 Autoimmune disease, 104, 124 Autoimmunity, 18, 104 Autonomic, 101, 104, 127, 128 Autonomic Nervous System, 104, 127 Autopsy, 13, 14, 51, 104 Avian, 11, 104 Axonal, 9, 36, 104 Axons, 104, 124, 126, 132 B Bacteria, 103, 104, 105, 113, 114, 123, 131, 132, 137, 138 Bacterial Physiology, 101, 105 Bacteriophage, 105, 119, 137 Basal Ganglia, 43, 60, 104, 105, 106 Basal Ganglia Diseases, 104, 105 Basement Membrane, 105, 114 Basophils, 105, 121 Benign, 105, 106, 117, 125, 127 Beta-Galactosidase, 37, 70, 105 Bilateral, 105, 127 Bile, 105, 115, 121, 135 Biochemical, 4, 8, 11, 23, 28, 29, 35, 37, 39, 43, 55, 70, 74, 75, 76, 102, 105, 116, 120, 133 Biological Transport, 105, 112 Biopsy, 24, 31, 105 Biosynthesis, 105, 121, 130 Biotechnology, 19, 83, 105 Bladder, 58, 105, 118, 124, 138 Blood pressure, 105, 134 Blood vessel, 105, 106, 108, 113, 120, 123, 131, 134, 135, 136, 138 Body Fluids, 106, 112, 134 Bone Marrow Transplantation, 9, 15, 22, 23, 29, 32, 41, 43, 45, 46, 47, 48, 56, 57, 59, 60, 61, 106

142

Leukodystrophy

Bowel, 103, 106 Bradykinin, 106, 126 Brain Neoplasms, 106, 118, 136 Brain Stem, 106, 107 Breeding, 18, 106 Buccal, 106, 135 C Cachexia, 11, 14, 106 Calcification, 43, 106 Calcium, 106, 109, 123 Carbohydrate, 106, 116 Carcinogenic, 107, 119, 126, 130, 135 Cardiac, 107, 112, 124, 135 Carrier State, 32, 107 Case report, 24, 25, 107 Catalytic Domain, 74, 76, 107 Catheters, 18, 107 Cell Death, 11, 103, 107, 125 Cell Division, 104, 107, 111, 120, 123, 128, 133 Cell membrane, 105, 107, 124 Cell Respiration, 101, 107, 123, 127 Cell Transplantation, 11, 15, 19, 38, 107 Central Nervous System Infections, 107, 117, 118 Ceramide, 37, 107, 115 Cerebellar, 9, 20, 29, 31, 104, 107, 131 Cerebellum, 51, 106, 107, 131 Cerebral, 18, 24, 25, 27, 30, 31, 33, 41, 104, 105, 106, 107, 108, 118, 122, 130, 134, 136 Cerebral Cortex, 104, 107 Cerebral Palsy, 107, 134 Cerebrospinal, 29, 107, 108, 118 Cerebrospinal fluid, 29, 108, 118 Cerebrum, 107, 108, 136, 137 Character, 22, 108, 111 Chin, 108, 123 Cholecystitis, 38, 108 Cholesterol, 9, 105, 108, 121, 135 Chondrocytes, 108, 114 Chorion, 108 Chorionic Villi, 34, 56, 108 Choroid, 108, 132 Chromatin, 103, 108, 113, 125 Chromosomal, 5, 102, 108, 132, 133 Chromosome, 12, 14, 33, 34, 35, 108, 117, 120, 121, 133, 137 Chronic, 8, 11, 20, 26, 35, 38, 106, 108, 119, 135 Chronic Disease, 106, 108 Cirrhosis, 16, 108 CIS, 31, 108, 132

Clinical trial, 3, 10, 83, 108, 131 Cloning, 27, 105, 108 Cochlea, 108 Cochlear, 25, 108 Codon, 4, 108, 116 Coenzyme, 109, 121, 130 Collagen, 102, 105, 109, 114, 128 Colloidal, 109, 113 Complement, 109, 120 Complementary and alternative medicine, 69, 71, 109 Complementary medicine, 69, 109 Complementation, 19, 35, 109 Computational Biology, 83, 109 Computed tomography, 43, 110 Computerized axial tomography, 110 Computerized tomography, 110 Conception, 110, 114 Conduction, 21, 41, 50, 110, 124 Conjugated, 110, 111 Conjunctiva, 110, 119 Connective Tissue, 106, 109, 110, 112, 114, 115, 121, 123 Consciousness, 110, 112 Constriction, 110, 120, 133 Contraindications, ii, 110 Coordination, 17, 107, 110, 124 Coronary, 110, 123 Coronary Thrombosis, 110, 123 Cortex, 110, 114, 129, 131 Cortical, 29, 31, 110, 133, 136 Cranial, 107, 110, 117, 120, 126, 127 Craniocerebral Trauma, 105, 110, 117, 118, 136 Crossing-over, 111, 131 Crystallization, 17, 111 Cultured cells, 28, 111 Cutaneous, 29, 111 Cyclic, 111, 117, 126, 128 Cycloserine, 11, 66, 111 Cysteine, 10, 38, 111 Cystine, 111 Cytochrome, 29, 30, 111, 127 Cytochrome-c Oxidase, 30, 111 Cytogenetics, 5, 111, 133 Cytokine, 10, 111 Cytoplasm, 103, 105, 107, 111, 113, 119, 124, 125, 132, 138 Cytoskeleton, 4, 111, 123 Cytotoxic, 11, 55, 111 D Degenerative, 4, 88, 111

143

Deletion, 4, 20, 30, 103, 111 Delusions, 111, 130 Dementia, 20, 21, 22, 25, 29, 31, 112 Demyelinating Diseases, 112, 124 Denaturation, 112, 129 Dendrites, 112, 125 Density, 17, 112, 126, 134 Deprivation, 11, 112 Dermatosis, 112, 114 Dermis, 112, 135 Desmin, 112, 119 Diagnostic procedure, 73, 112 Diffusion, 48, 49, 105, 112, 119 Digestion, 58, 105, 106, 112, 121, 135, 138 Dilation, 106, 112, 118 Dimerization, 50, 112 Diploid, 109, 112, 128 Direct, iii, 8, 112, 132 Dissociation, 101, 112, 120 Distal, 104, 112, 128 Duct, 112, 132, 135 Dysgenesis, 21, 47, 112 Dysostosis, 112, 122 Dystrophy, 5, 58, 113 E Effector, 61, 101, 109, 113, 128 Efficacy, 10, 15, 113 Electrolyte, 113, 134 Electrons, 113, 120, 122, 127, 131 Electrophoresis, 32, 34, 113 Electrophysiological, 10, 113 Elementary Particles, 113, 122, 130 Embryo, 113, 119, 129, 137 Encephalopathy, 41, 113 Endemic, 113, 122, 134 Endothelial cell, 113, 114, 136 Endothelium, 113, 125 Endothelium-derived, 113, 125 Endotoxic, 113, 121 Environmental Health, 82, 84, 113 Enzymatic, 32, 48, 52, 56, 75, 102, 106, 107, 109, 113, 129, 132 Eosinophils, 113, 121 Epithelial, 62, 105, 114, 127 Epithelial Cells, 62, 114 Erythrocytes, 103, 106, 114 Eukaryotic Cells, 114, 126 Evoked Potentials, 43, 69, 114 Exhaustion, 114, 122 Exogenous, 9, 114, 115 Extracellular, 8, 104, 110, 114, 134 Extracellular Matrix, 8, 110, 114

Extracellular Space, 114 Extremity, 114, 127 Eye Infections, 101, 114 F Facial, 31, 114, 122 Family Planning, 83, 114 Fat, 106, 107, 114, 121, 124, 134 Fetus, 18, 114, 128, 129, 137 Fibroblast Growth Factor, 8, 114 Fibroblasts, 9, 14, 19, 35, 36, 44, 54, 60, 61, 74, 76, 114 Fibrosis, 18, 114, 133 Filariasis, 18, 114 Fluorescence, 5, 115 Fold, 17, 115 Fossa, 107, 115 Fungi, 114, 115, 123, 138, 139 G Galactosides, 105, 115 Galactosylceramidase, 19, 21, 35, 115 Gallbladder, 54, 55, 63, 64, 108, 115 Ganglia, 101, 105, 115, 125, 127, 128 Gas, 102, 112, 115, 125, 138 Gastrointestinal, 14, 58, 106, 115, 122, 133, 135 Gastrointestinal Hemorrhage, 58, 115 Gastrointestinal tract, 115, 133 Gels, 75, 115 Gene Duplication, 5, 115 Gene Expression, 12, 115 Gene Targeting, 35, 115 Gene Therapy, 5, 8, 11, 36, 41, 54, 60, 61, 101, 115 Genes, pol, 74, 76, 116 Genetic Code, 116, 126 Genetic Screening, 5, 74, 76, 116 Genetic testing, 116, 129 Genotype, 36, 39, 49, 50, 116, 128 Gestation, 116, 127, 128 Gland, 62, 116, 121, 127, 128, 133, 135 Glioma, 46, 116 Glomeruli, 116, 131 Glucose, 29, 116, 119, 128, 132 Glutathione Peroxidase, 116, 133 Glycine, 102, 116, 125 Glycogen, 116, 128 Glycoprotein, 8, 116, 124, 136 Glycosidic, 116, 128 Glycosylation, 22, 41, 116 Gonadal, 116, 135 Governing Board, 116, 129 Graft, 14, 24, 116, 117

144

Leukodystrophy

Graft Rejection, 24, 117 Grafting, 14, 117 Guanylate Cyclase, 117, 126 H Habitual, 108, 117 Headache, 117, 118, 119 Hematogenous, 9, 117 Hematopoietic Stem Cells, 11, 19, 117 Heme, 111, 117 Hemoglobinopathies, 115, 117 Hemophilia, 18, 117 Hemorrhage, 110, 117, 135 Hereditary, 5, 7, 38, 117, 125 Heredity, 36, 115, 116, 117 Herpes, 8, 117 Herpes Zoster, 117 Heterogeneity, 27, 38, 102, 117 Heterozygote, 22, 57, 117 Histology, 74, 76, 117 Homologous, 13, 102, 111, 115, 117, 133, 137 Homozygotes, 30, 117 Hormonal, 104, 117 Hormone, 117, 119, 122, 129 Humoral, 117, 118 Hydrocephalus, 58, 118, 120 Hydrolases, 118, 121 Hydrolysis, 8, 74, 76, 105, 118, 129, 130 Hydrophobic, 8, 118 Hydroxyproline, 102, 109, 118 Hypotonia, 74, 76, 118 I Iduronidase, 48, 118 Immune response, 18, 103, 104, 117, 118, 135, 138 Immune system, 104, 118, 121, 124, 139 Immunogenic, 118, 121 Impairment, 104, 114, 118, 123, 130 In vitro, 5, 6, 13, 14, 18, 34, 61, 115, 118, 129, 136 In vivo, 11, 14, 15, 41, 66, 115, 118 Incision, 118, 120 Incontinence, 118 Incubated, 10, 118 Incubation, 118, 120 Incubation period, 118, 120 Individuality, 18, 118 Induction, 6, 10, 11, 119 Infancy, 119 Infantile, 16, 21, 22, 23, 24, 26, 29, 33, 34, 37, 38, 39, 41, 45, 51, 52, 56, 63, 119 Infarction, 110, 118, 119, 123

Infection, 11, 43, 104, 107, 114, 119, 120, 121, 125, 131, 135, 139 Infiltration, 9, 119 Inflammation, 9, 108, 112, 114, 117, 119, 129, 131, 135 Influenza, 43, 119 Infusion, 22, 119 Initiation, 6, 119, 137 Innervation, 119, 126, 131 Insulator, 119, 124 Insulin, 10, 11, 119 Insulin-dependent diabetes mellitus, 119 Insulin-like, 10, 11, 119 Integrase, 116, 119 Intermediate Filament Proteins, 18, 119 Intermediate Filaments, 4, 18, 120 Interphase, 5, 120 Intestines, 115, 120 Intracellular, 7, 9, 14, 119, 120, 121, 122, 126, 132, 133 Intracranial Hemorrhages, 118, 120, 136 Intracranial Hypertension, 117, 118, 120, 127 Intravenous, 119, 120 Invasive, 16, 120, 122 Involuntary, 105, 120, 124, 136 Ion Channels, 104, 120 Ionization, 26, 120 Ions, 112, 113, 120 Ischemia, 104, 120 K Karyotypes, 116, 120 Kb, 82, 120 L Lectin, 40, 120, 122 Lentivirus, 8, 120 Lesion, 55, 120, 121 Lethargy, 118, 120 Leukemia, 116, 121 Leukocytes, 29, 30, 44, 64, 105, 106, 113, 121, 124, 125 Linkages, 118, 121 Lipid, 9, 17, 39, 55, 119, 121, 124 Lipid A, 55, 121 Lipopolysaccharides, 121 Liposomes, 70, 121 Liver, 16, 18, 40, 60, 74, 76, 105, 108, 115, 116, 121, 137 Localization, 35, 121 Localized, 12, 66, 74, 76, 112, 119, 121, 128 Lovastatin, 10, 121 Low-density lipoprotein, 121

145

Lymph, 113, 121 Lymph node, 121 Lymphatic, 18, 113, 119, 121, 123, 134, 136 Lymphocyte, 4, 103, 121 Lymphoid, 30, 103, 121 Lysosomal Storage Diseases, 53, 121 Lysosome, 17, 121 M Magnetic Resonance Imaging, 15, 37, 59, 122 Magnetic Resonance Spectroscopy, 15, 66, 122 Malaria, 18, 122 Malaria, Falciparum, 122 Malaria, Vivax, 122 Malformation, 33, 58, 122 Malnutrition, 11, 104, 106, 122 Mammogram, 106, 122, 123 Manic, 122, 130 Manifest, 104, 122 Mannosidosis, 24, 122 Mediate, 9, 122 MEDLINE, 83, 122 Megalencephaly, 48, 74, 76, 122 Membrane, 8, 53, 104, 107, 108, 109, 110, 111, 114, 120, 121, 122, 124, 125, 126, 132, 139 Membrane Proteins, 121, 122 Memory, 112, 122 Meninges, 107, 110, 123, 134 Mental, iv, 3, 23, 74, 76, 82, 84, 107, 108, 112, 122, 123, 130 Mental Disorders, 123, 130 Mental Retardation, 74, 76, 123 Mesenchymal, 22, 123 Metabolite, 121, 123 MI, 99, 123 Microbe, 123, 136 Microbiology, 101, 104, 123 Microcalcifications, 106, 123 Microfilaments, 120, 123 Microglia, 104, 123 Microorganism, 123, 139 Microtubules, 120, 123 Migration, 14, 123 Mitochondria, 13, 74, 76, 123, 126 Mitochondrial Swelling, 123, 125 Mitosis, 103, 123 Modeling, 5, 124 Modification, 102, 124 Molecule, 103, 109, 112, 113, 116, 117, 118, 120, 124, 127, 128, 129, 131, 137, 138

Monocytes, 121, 124 Morphological, 4, 6, 113, 124 Morphology, 6, 124 Mucins, 124, 132 Mucosa, 124, 135 Mucositis, 124, 136 Multiple sclerosis, 12, 26, 35, 38, 124 Muscular Diseases, 124, 127 Muscular Dystrophies, 113, 124 Mutism, 33, 124 Myalgia, 119, 124 Myelin, 4, 7, 9, 11, 12, 26, 39, 74, 76, 112, 124, 126 Myelin Proteins, 12, 124 Myelin Sheath, 7, 124, 126 Myocardium, 123, 124 N Nasal Mucosa, 119, 125 NCI, 1, 81, 108, 125 Necrosis, 12, 103, 114, 119, 123, 125 Neoplasm, 125, 127 Nervous System, 4, 6, 7, 8, 14, 15, 16, 17, 24, 63, 101, 104, 106, 107, 114, 115, 123, 124, 125, 126, 127, 133 Networks, 18, 125 Neural, 6, 14, 15, 118, 123, 125 Neurodegenerative Diseases, 9, 13, 15, 105, 125 Neurologic, 8, 118, 125 Neuromuscular, 101, 125, 126 Neuromuscular Junction, 101, 125, 126 Neuronal, 9, 33, 51, 125 Neurons, 6, 9, 62, 112, 115, 125 Neuropathy, 5, 35, 36, 52, 125, 128 Neuropeptides, 18, 125 Neurotransmitter, 101, 102, 106, 116, 120, 125, 135 Neutrophils, 121, 125 Nitric Oxide, 10, 125 Nuclear, 53, 105, 113, 114, 125, 126, 132 Nuclei, 102, 113, 115, 122, 123, 126, 130 Nucleic acid, 74, 76, 116, 126 Nucleus, 103, 104, 105, 108, 111, 113, 114, 120, 124, 125, 126, 130, 135, 136 O Ocular, 52, 53, 126 Oligodendroglia, 124, 126 Oligodendroglial, 6, 126 Oncogenic, 120, 126 Opacity, 112, 126 Open Reading Frames, 120, 126 Ophthalmoplegia, 33, 126

146

Leukodystrophy

Optic Chiasm, 126 Optic Nerve, 35, 126, 132 Organelles, 13, 111, 124, 126, 128 Oxidation, 103, 111, 116, 126 Oxidative metabolism, 101, 127 Oxidative Phosphorylation, 13, 127 Oxides, 14, 127 P Palate, 127, 135 Pancreas, 119, 127, 133 Papilloma, 64, 127 Paralysis, 126, 127, 131, 134 Paraparesis, 23, 31, 127 Paroxetine, 60, 127 Particle, 127, 134, 137 Pathogenesis, 9, 13, 14, 18, 23, 74, 76, 127 Pathologic, 103, 105, 110, 127, 132, 134 Pathologic Processes, 103, 127 Pathophysiology, 7, 15, 127 Patient Education, 89, 94, 96, 99, 127 Pelvis, 101, 127, 131 Peptide, 102, 114, 118, 127, 129, 130 Perinatal, 51, 127 Peripheral Nervous System, 8, 112, 124, 125, 127, 128, 135 Peripheral Nervous System Diseases, 127, 128 Peripheral Neuropathy, 14, 42, 46, 128 Pharmacologic, 128, 137 Pharynx, 119, 128 Phenotype, 5, 39, 41, 49, 50, 53, 54, 109, 128 Phenylacetate, 10, 128 Phosphodiesterase, 7, 128 Phosphorylase, 14, 128 Phosphorylated, 16, 109, 128 Phosphorylation, 111, 128 Physiologic, 105, 128, 131, 132 Physiology, 50, 66, 113, 128 Pituitary Gland, 114, 128 Placenta, 108, 128, 129, 137 Plants, 106, 116, 120, 124, 128, 132, 137 Plasma, 14, 103, 107, 128 Plasma cells, 103, 128 Plastids, 126, 128 Platelet Aggregation, 126, 128 Platelets, 126, 128, 129, 133 Pneumonia, 110, 129 Point Mutation, 14, 29, 129 Polymerase, 58, 116, 129 Polymerase Chain Reaction, 58, 129 Polypeptide, 74, 76, 102, 109, 129, 130, 139

Posterior, 103, 104, 107, 108, 127, 129 Postnatal, 129, 135 Potentiates, 10, 129 Practice Guidelines, 84, 129 Preclinical, 62, 129 Precursor, 113, 129 Prenatal, 34, 41, 56, 60, 113, 116, 129 Prenatal Diagnosis, 34, 41, 129 Prevalence, 38, 56, 129 Progesterone, 129, 135 Progression, 9, 60, 103, 129 Progressive, 6, 10, 23, 26, 27, 33, 35, 38, 57, 89, 108, 112, 124, 125, 129, 130 Progressive disease, 89, 130 Projection, 126, 130, 131 Promoter, 11, 130 Protease, 116, 130 Protein C, 18, 102, 105, 108, 130, 137 Protein Conformation, 102, 130 Protein S, 105, 116, 130, 132 Proteolytic, 8, 102, 109, 130 Protons, 111, 122, 130, 131 Protozoa, 123, 130, 138 Protozoan, 107, 122, 130 Psychiatric, 23, 57, 75, 123, 130 Psychiatry, 21, 22, 23, 45, 60, 75, 130 Psychic, 123, 130, 133 Psychomotor, 122, 130 Psychosine, 4, 8, 10, 11, 19, 32, 37, 130 Psychosis, 48, 57, 130 Ptosis, 14, 131 Public Policy, 83, 131 Publishing, 19, 89, 131 Pyelonephritis, 18, 131 R Race, 120, 123, 131 Radiation, 113, 115, 131, 139 Radioactive, 120, 126, 131 Radiological, 46, 58, 131 Radiology, 14, 23, 46, 50, 63, 131 Randomized, 113, 131 Reactive Oxygen Species, 7, 131 Reality Testing, 130, 131 Receptor, 10, 101, 103, 114, 131, 133 Recessive gene, 4, 131 Recombinant, 17, 131, 138 Recombination, 13, 115, 131 Red Nucleus, 104, 131 Reductase, 121, 131 Refer, 1, 106, 109, 115, 117, 121, 130, 132 Regeneration, 114, 132 Regimen, 111, 113, 132

147

Resorption, 118, 132 Retina, 63, 108, 126, 132, 139 Retinal, 126, 132 Retinal Ganglion Cells, 126, 132 Retroperitoneal, 101, 132 Retroviral vector, 5, 115, 132 Retrovirus, 11, 132 Ribose, 132, 136 Ribosome, 132, 137 Rickettsiae, 132, 138 S Saliva, 30, 132 Salivary, 132 Salivary glands, 132 Saponins, 132, 135 Satellite, 17, 126, 133 Sclerosis, 16, 30, 124, 133 Screening, 5, 74, 76, 108, 116, 133 Secretion, 101, 119, 123, 124, 133, 138 Secretory, 12, 133 Segregation, 131, 133 Seizures, 55, 58, 59, 133 Selenium, 17, 133 Selenomethionine, 17, 133 Sequencing, 4, 129, 133 Serotonin, 125, 127, 133 Serum, 44, 109, 121, 133 Shock, 4, 133, 137 Side effect, 133, 136 Skeletal, 14, 23, 112, 118, 124, 133 Skeleton, 101, 133 Skull, 110, 133, 136 Small intestine, 117, 120, 133, 138 Sodium, 10, 133, 135 Soft tissue, 106, 126, 133, 134 Soma, 134 Somatic, 19, 35, 118, 123, 127, 128, 134 Sound wave, 110, 134 Spastic, 5, 23, 31, 134 Specialist, 90, 112, 134 Species, 35, 102, 107, 112, 120, 122, 123, 124, 131, 134, 135, 137, 138, 139 Specificity, 54, 102, 134 Sperm, 108, 134 Spinal cord, 104, 106, 107, 108, 123, 125, 127, 128, 134 Spinal Cord Diseases, 127, 134 Spinal Nerves, 127, 134 Spleen, 121, 134 Sporadic, 125, 134 Stabilization, 47, 134 Stem cell transplantation, 11, 14, 134

Stem Cells, 14, 134, 137 Steroid, 32, 132, 135 Stimulus, 114, 119, 120, 135 Stomach, 115, 117, 120, 128, 133, 134, 135 Stomatitis, 8, 135 Strand, 129, 135 Stress, 7, 11, 104, 135 Stroke, 11, 82, 88, 135 Subacute, 119, 135 Subclinical, 119, 133, 135 Subspecies, 134, 135 Substance P, 111, 123, 133, 135 Substrate, 11, 15, 107, 118, 135 Supplementation, 11, 135 Support group, 89, 135 Sweat, 44, 62, 112, 135 Sweat Glands, 44, 112, 135 Symptomatology, 57, 60, 135 Synergistic, 135, 136 Systemic, 105, 119, 120, 135 T Telangiectasia, 25, 135 Telencephalon, 105, 107, 136 Temporal, 9, 15, 29, 102, 136 Thalamic, 31, 60, 104, 136 Thalamic Diseases, 104, 136 Thermal, 112, 129, 136 Thrombin, 128, 130, 136 Thrombomodulin, 130, 136 Thrombosis, 130, 135, 136 Thymidine, 14, 136 Thymidine Phosphorylase, 14, 136 Thymus, 121, 136 Tic, 4, 136 Tissue Culture, 136, 138 Tomography, 122, 136 Tone, 118, 136 Tooth Preparation, 101, 136 Toxic, iv, 7, 125, 133, 136, 137 Toxicity, 16, 136 Toxicology, 84, 137 Toxins, 103, 119, 137 Transcriptase, 116, 132, 137 Transcription Factors, 17, 137 Transduction, 8, 60, 137 Transfection, 13, 14, 105, 115, 137 Transferases, 116, 137 Transgenes, 13, 16, 137 Translation, 6, 7, 12, 102, 137 Translocating, 8, 137 Transmitter, 101, 104, 120, 137 Transplantation, 15, 19, 22, 24, 25, 137

148

Leukodystrophy

Trauma, 125, 137 Tuberculosis, 111, 137 Tuberous Sclerosis, 16, 137 U Umbilical Arteries, 137 Umbilical Cord, 48, 137 Umbilical cord blood, 48, 137 Urea, 135, 137 Urethra, 138 Urinary, 26, 39, 111, 118, 138 Urinary tract, 111, 138 Urinary tract infection, 111, 138 Urine, 63, 74, 76, 105, 118, 138 V Vaccines, 18, 138 Vacuoles, 126, 138 Vascular, 18, 108, 112, 113, 119, 125, 128, 134, 138 Vasodilators, 126, 138 VE, 12, 138 Vector, 8, 11, 60, 137, 138 Vein, 120, 126, 133, 137, 138 Ventricles, 108, 118, 138 Ventricular, 118, 138

Vesicular, 8, 117, 138 Veterinary Medicine, 83, 138 Villi, 56, 118, 138 Villus, 5, 138 Vimentin, 18, 119, 138 Viral, 11, 119, 126, 132, 137, 138 Viral vector, 11, 138 Virulence, 104, 136, 138 Virus, 8, 14, 18, 105, 107, 132, 137, 138 Viscera, 134, 139 Vitreous, 132, 139 Vitreous Body, 132, 139 Vitro, 6, 13, 139 Vivo, 11, 14, 139 W White blood cell, 103, 118, 121, 128, 139 Wound Healing, 114, 139 X Xenograft, 103, 139 X-ray, 110, 115, 122, 126, 131, 139 Y Yeasts, 115, 128, 139 Z Zymogen, 130, 139