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

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Epidermolysis Bullosa: 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: 0-497-00409-7 1. Epidermolysis Bullosa-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on epidermolysis bullosa. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON EPIDERMOLYSIS BULLOSA ........................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Epidermolysis Bullosa................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. NUTRITION AND EPIDERMOLYSIS BULLOSA............................................................... 75 Overview...................................................................................................................................... 75 Finding Nutrition Studies on Epidermolysis Bullosa.................................................................. 75 Federal Resources on Nutrition ................................................................................................... 77 Additional Web Resources ........................................................................................................... 78 CHAPTER 3. ALTERNATIVE MEDICINE AND EPIDERMOLYSIS BULLOSA ........................................ 79 Overview...................................................................................................................................... 79 National Center for Complementary and Alternative Medicine.................................................. 79 Additional Web Resources ........................................................................................................... 82 General References ....................................................................................................................... 82 CHAPTER 4. PATENTS ON EPIDERMOLYSIS BULLOSA ..................................................................... 83 Overview...................................................................................................................................... 83 Patents on Epidermolysis Bullosa................................................................................................ 83 Patent Applications on Epidermolysis Bullosa ............................................................................ 85 Keeping Current .......................................................................................................................... 86 CHAPTER 5. BOOKS ON EPIDERMOLYSIS BULLOSA ......................................................................... 87 Overview...................................................................................................................................... 87 Book Summaries: Federal Agencies.............................................................................................. 87 Chapters on Epidermolysis Bullosa.............................................................................................. 88 CHAPTER 6. PERIODICALS AND NEWS ON EPIDERMOLYSIS BULLOSA ........................................... 89 Overview...................................................................................................................................... 89 News Services and Press Releases................................................................................................ 89 Academic Periodicals covering Epidermolysis Bullosa ................................................................ 91 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 93 Overview...................................................................................................................................... 93 U.S. Pharmacopeia....................................................................................................................... 93 Commercial Databases ................................................................................................................. 94 Researching Orphan Drugs ......................................................................................................... 94 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 99 Overview...................................................................................................................................... 99 NIH Guidelines............................................................................................................................ 99 NIH Databases........................................................................................................................... 101 Other Commercial Databases..................................................................................................... 103 APPENDIX B. PATIENT RESOURCES ............................................................................................... 105 Overview.................................................................................................................................... 105 Patient Guideline Sources.......................................................................................................... 105 Associations and Epidermolysis Bullosa.................................................................................... 107 Finding Associations.................................................................................................................. 108 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 111 Overview.................................................................................................................................... 111 Preparation................................................................................................................................. 111 Finding a Local Medical Library................................................................................................ 111 Medical Libraries in the U.S. and Canada ................................................................................. 111

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ONLINE GLOSSARIES................................................................................................................ 117 Online Dictionary Directories ................................................................................................... 118 EPIDERMOLYSIS BULLOSA DICTIONARY ......................................................................... 119 INDEX .............................................................................................................................................. 163

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with epidermolysis bullosa 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 epidermolysis bullosa, 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 epidermolysis bullosa, 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 epidermolysis bullosa. 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 epidermolysis bullosa, 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 epidermolysis bullosa. The Editors

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and epidermolysis bullosa, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “epidermolysis bullosa” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Comprehensive Dental Care and General Anesthetic Management of Hereditary Epidermolysis Bullosa: A Review of Fourteen Cases Source: Oral Surgery, Oral Medicine, Oral Pathology. Volume 70: 573-578. November 1990. Summary: Dental management of persons with epidermolysis bullosa remains challenging because of the severe hard and soft tissue manifestations of these diseases. This article reports on a study that reviewed the dental treatment of 14 cases requiring 24 general anesthetics. Twenty-three of the cases were managed with oral tracheal intubation to accomplish full-mouth dental rehabilitation. Dental therapy consisted of preventive, restorative, and surgical procedures. There were no serious postoperative complications and no airway problems were experienced. Although extensive intraoral

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mucosal blistering did occur in several cases, postoperative healing progressed normally. The author notes that soft tissue trauma may be lessened through the use of small suction tips, flat tissue retractors, and extensive lubrication of all tissues requiring manipulation. 4 figures. 3 tables. 30 references. (AA-M). •

Sucralfate: A Help During Oral Management in Patients with Epidermolysis Bullosa Source: Journal of Periodontology. 72(5): 691-695. May 2001. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Epidermolysis bullos (EB) is a group of genetic disorders that lead to blister formation at variable depths in skin and mucosa. Vesicles (blisters) may arise spontaneously or be caused by friction or trauma. Oral tissue fragility and blistering is common in all EB types. The majority of patients with mild forms of EB are able to receive dental treatment. The prevention of dental caries is most challenging in subjects with severe mucosal involvement, as they are least able to routinely undergo correct preventive procedures. This article reports on a study undertaken to evaluate the effectiveness of a sucralfate suspension in reducing both pain and the number of blisters in patients with EB, and to obtain improved oral hygiene and a lower incidence of caries (cavities). Five patients with dystrophic EB were treated with sucralfate suspension for the prevention and management of oral blisters. Oral blisters were assessed using a quantitative scale, while pain was assessed using visual analog scale (VAS), and hygiene was evaluated through plaque and gingival indices. Results showed that the number of blisters, oral pain, and plaque decreased in all cases. The authors conclude that oral prophylaxis with sucralfate prevented oral blisters and oral discomfort. The procedure proved to be cost effective and easy to administer. There were no significant side effects. This treatment may be used routinely in patients with EB. 4 figures. 37 references.

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Epidermolysis Bullosa Acquisita: Clinical Manifestations, Microscopic Findings, and Surgical Periodontal Therapy. A Case Report Source: Journal of Periodontology. 72(4): 550-558. April 2001. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Epidermolysis bullosa acquisita (EBA) is an uncommon, acquired, chronic subepidermal (under the skin) bullous disease. This article describes a case of EBA with gingival (gum) involvement. A 43 year old woman with EBA was referred to the authors' clinic for periodontal therapy because of gingival tenderness and bleeding. She had been on cyclosporin A therapy for 2 years. Clinical findings were analyzed and samples obtained during surgery (anterior gingivectomy, or gum removal) were examined. The dentition displayed minimal enamel hypoplasia (undergrowth). Decayed, missing, and filled surfaces score (DMFS) was found to be elevated. Periodontal examination showed generalized diffuse gingival inflammation and gingival enlargement localized mainly to the anterior region. Nikolsky's sign (a measure of skin separation) was positive. However, wound healing was uneventful after the operations. Microscopic findings were similar to those obtained from the skin. Twentyone months after the operations, Nikolsky's sign was negative and no remarkable gingival inflammation was noted. Microscopic examination revealed that the blisters were fewer in number and smaller in size. These results indicate that gingival tissues may also be involved in EBA. Uneventful wound healing after periodontal surgery in this case suggests that periodontal surgery can be performed in patients with EBA.

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Additionally, these findings imply that gingivectomy proves useful in maintaining gingival integrity in these patients. The authors note that their data also suggest that patients with EBA are highly likely to develop dental caries (cavities). 12 figures. 28 references. •

Combined Medical-Dental Treatment of an Epidermolysis Bullosa Patient Source: SCD. Special Care in Dentistry. 11(4): 148-150. July-August 1991. Summary: Epidermolysis bullosa presents a wide range of clinical symptoms. This article presents a case of a patient with recessive dystrophic epidermolysis bullosa that required dental treatment. Standard protocol modifications and medical considerations were required in preparation for general anesthesia. The management of a systemicallydebilitated patient is discussed, with emphasis on the need for health care providers to seek multi-disciplinary treatment for such patients. The authors recommend postoperative follow-up steps, including monitoring the relationship of the patient's disease state to dental health. 3 figures. 14 references. (AA-M).

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Dental Problems in Junctional Epidermolysis Bullosa: Report of a Case with Treatment Considerations Source: Annals of Dentistry. 54(1-2): 14-17. Summer-Fall 1995. Summary: This article describes epidermolysis bullosa (EB) and reports a case of dental problems in a patient with junctional EB. Epidermolysis bullosa refers to a heterogenous group of heritable diseases characterized by marked fragility of the skin. Depending on the specific type, severity varies from occasional presence of blisters with little functional impairment, to widespread blistering of the skin and mucosa which can be fatal in the neonatal period. Various dental abnormalities occur in EB, and can include small, conical teeth, and disturbances of enamel formation. The case report tells of a 26 year old African American man with enamel dysplasia in all teeth and bilateral absence of maxillary central and lateral incisors. The authors describes the periodontal and prosthetic dental procedures undertaken with this patient. The authors stress this case shows that, with appropriate precautions, even a patient with widespread cutaneous erosions caused by junctional EB can tolerate extensive dental manipulation with gratifying results. They also note that, because enamel defects and frequent caries can be a major problem in EB, preventive dental care to minimize caries development is important. 4 figures. 17 references. (AA-M).

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Oral Epidermolysis Bullosa in Adults Source: SCD. Special Care in Dentistry. 15(4): 144-148. July-August 1995. Summary: This article reports on a rare case of epidermolysis bullosa (EB) in an adult; the related English language dental literature of the last 20 years is also reviewed. The authors suggest special dental management, stressing that dental care and followup are very important to prevent extensive deterioration of the oral mucosal tissues; identify early malignant transformation that may occur in adult patients with EB; and prevent rampant caries that could cause destruction of the EB patient's dentition. The authors provide a chart of the EB cases reported in the dental literature. Oral mucosal malignant transformation in adult EB patients has been reported. The authors stress that the serious complications of this transformation may be intercepted by frequent recall examinations, during which the following should take place: prophylaxis, scaling, root planing, topical fluorides, antibacterial mouthrinses, pit and fissure sealants, and reinforcing oral hygiene. 1 figure. 5 tables. 15 references. (AA-M).

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Dental Maturity in Children with Dystrophic Epidermolysis Bullosa Source: Pediatric Dentistry. 22(5): 385-388. September-October 2000. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: This article reports on a study that was performed to compare dental age (DA) of children with dystrophic epidermolysis bullosa recessiva (DEBr) with the DA of healthy children. Orthopantomographs (OPGs) of children with DEBr were compared with those of healthy children; a total of 48 pairs of OPGs were compared. There was a considerable range of variation in the difference between the chronological age and the dental age of both groups. This varied from minus 2 years 8 months to plus 3 years for the control children and minus 3 years 1 month to plus 3 years 4 months for the DEBr children. Despite this wider range, the average DA of children with DEBr was statistically significantly delayed by 2 years 3 months. The authors conclude that the delay in dental development of children with DEBs may have an impact on the clinical management of these children. Knowledge of dental age is useful to the orthodontist, pediatric dentist, pediatrician, and to the pediatric endocrinologist in order to plan and evaluate treatment. 3 figures. 2 tables. 19 references.

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

Project Title: ACCURATE CONSTRUCTION

EPITHELIAL/MESENCHYME

SKIN

ORGAN

Principal Investigator & Institution: Hoeffler, Warren K.; Xgene Corporation 863C Mitten Rd Burlingame, Ca 940101303 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2005 Summary: (provided by applicant): The future of organ engineering and regeneration depends upon finding a method to successfully orient tissue layers formed from different cell types, typically epithelial/mesenchyme combinations. Modeling methods 2

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

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to make human skin have so far focused on constructing separate layers first and then layering one tissue type on the other to mimic the complete skin organ, and is the dominant method used today. In contrast, during embryogenesis and wound repair distinct tissue layers form simultaneously through a process relying on the cellular binding properties of cell populations. We have tapped into this innate ability of cell populations to recognize other cells of their type by creating a skin reconstitution method called a cell skin equivalent, or CeSSE ('cease'). Our skin model has been commercialized as "AccuskinTM" and we propose to characterize the skin formed and compare it to skin produced by another method, broadly known as the composite method. Immunohistology will be conducted to both illustrate the presence of common skin markers and to highlight differences in protein marker distribution observed in the two models and as compared to normal human skin. A key function of skin is to provide a barrier to the outside environment and a comparison of barrier properties will be assessed for the two different models by measuring cell viability in response to exposure to skin irritants by MTT assay. Cytokine production levels (IL1alpha and TNFalpha) in the models will also be compared. In light of the favorable properties of Accuskin, its usefulness will be further shown by the ability to reconstruct diseased skin, exemplified by the mechano-bullosa disease recessive dystrophic epidermolysis bullosa, by using skin cells from cells derived from diseased patients. These proposed experiments will highlight broad functional differences in morphology, cell signaling between tissue layers, and stability/longevity between creating epithelial/mesenchyme tissue by cell sorting as compared to artificial layering of tissue used in composite models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONSEQUENCES STRUCTURE/FUNCTION

OF

MUTATIONS

IN

PROTEIN

Principal Investigator & Institution: Fertala, Andrzej; Associate Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Integrity and function of tissue depend on correct structure of extracellular and cellular components. Mutations in the genes coding for proteins critical for the structure and function of skin result in variety of pathological consequences. In order to understand the mechanisms that lead to loss of function of the dermal-epidermal junction in dystrophic epidermolysis bullosa we have undertaken the approach of analyzing the role of discrete procollagen VII domains in assembly of anchoring fibrils and mechanics of the dermal-epidermal junction. To achieve this goal we will generate a series of procollagen VII variants lacking specific domains. These variants will be then use to map sites critical for adhesion to other macromolecules and for collagen VII self-assembly. Second, we will characterize mechanical parameters of collagen VII monomer. Third, we will create a number of collagen VII mutants that will be used to determine how the single amino acid substitutions alter fibril assembly and change mechanical characteristics of collagen VII. We will also study effects of mutations in connexins that lead to erythrokeratodermia variabilis (EKV) and palmoplantar keratoderma (PPK). We will determine if mutations in connexin 26 and 31 change structure of the protein, disrupt formation of a hexamer and alter transmembrane transport of calcium. The goals of this project will be achieved by pursuing the following Specific Aims: (1) To map structural features in the noncollagenous domain 1 (NC1) critical for the function of collagen VII as an adhesive molecule; (2) To elucidate structural and biomechanical requirements for collagen VII

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assembly into anchoring fibrils; (3) To determine the effects of mutations in COL7A1 gene on assembly and mechanical properties of collagen VII; and (4) To determine the effects of distinct single amino acid substitutions in connexins on structure, assembly and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CELL AND TISSUE CULTURE Principal Investigator & Institution: Pfendner, Ellen; Assistant Professor & Manager; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): In the past, the Tissue Culture Core has been responsible for culturing both keratinocytes and fibroblasts from patients with inherited skin disorders as well as from their relatives and healthy control subjects. The clinical material, which will be obtained from Core E (Clinical and Administrative Core), as part of the clinical evaluation of the patients, will be transported for initiation of the cell cultures to the tissue culture facilities of the Tissue Culture Core of the Department of Dermatology and Cutaneous Biology. This core will also be responsible for maintenance and storage of these cells, as well as cultures being sent to us from other laboratories, so that they are available to the investigators in Projects 1-5. The future goals of this core include increasing the number of cell strains established from patients with different inherited skin disorders. Towards this goal, several of our participating clinical collaborators have pledged their support to continue providing patient material for our studies. We have also solicited several additional investigators who will serve as Consultants to our project. These investigators have expressed their willingness to share their clinical expertise and wealth of clinical material with us (see Core E). This network of international clinician-investigators guarantees the availability of a large number of new patients with distinct phenotypic subtypes to our studies. We have previously established collaborative contacts with the National EB Registry, and our collaboration with the Principal Investigators of the two clinical sites, Dr. Jo-David Fine (University of North Carolina, Chapel Hill), and Dr. Joseph McGuire (Stanford University), will help to ensure continued access to a large number of well-documented patients with EB. In addition, Dr. Uitto, Dr Richard, and other physicians in the dermatology clinic at Thomas Jefferson University expect to see a number of patients with the genetic disorders outlined in Project 1. Dr Richard has also established a foundation of clinical collaborators from whom patients will be referred. The availability of cultured cells from patients, as well as control cells from both unaffected healthy controls and from patients? relatives is essential to the success of projects 1 through 3, and project 5. Projects 1 and 2 require both mutant and normal cells to examine consequences of the genetic alterations at the protein level. Project 2 requires normal cell cultures to provide the mRNA and DNA needed for characterization of newly developed gene probes through Northern and Southern hybridizations. Projects 1 and 2 utilize cells from patients to identify and verify the existence of mutations at the DNA and RNA levels. Project 5 requires mutant and control cells, to test the feasibility of homologous recombination using chimeric RNA/DNA oligonucleotide constructs. This project will also utilize cells to study the expression of gene constructs as part of the testing of delivery systems. Project 1 also requires DNA for genetic linkage analyses. The DNA can be isolated from cultured cells, or from peripheral blood leukocytes, or from epithelial cells obtained by buccal cytobrushing. Due to the relative ease by which blood samples are obtained, peripheral blood will be used as the primary source of DNA, but

Studies

9

if blood samples are not available, cell cultures may be required also for Project 1. Although the handling of blood samples, and specifically the extraction of DNA, takes place in Project 1, selected blood samples will be transported to the Tissue Culture Core A for establishment of permanent lymphoblastoid cell lines. The second aim of the tissue culture core is to immortalize cells from patients with inherited skin disorders, in a manner such that the expression of the BMZ genes is not compromised. This particular function is important to assure availability of mutant keratinocytes from patients with different forms of inherited skin disorders. For protocols currently being utilized for immortalization of keratinocytes, as well as other cell types, see description below. The third aim of the tissue culture core is to provide DNA extracted from blood and tissues as well as cell cultures for projects 1 and 2 and to establish and maintain a DNA bank from all patient samples submitted for analysis. The DNA extraction and banking functions of the core will enable centralized access to DNA samples and allow retention of samples in the banking freezer for future use by members of the program m project and the dermatological community at large. In addition documents pertaining to patient contact, phenotype and other clinical information will be accessed and filed through the Administrative Core in conjunction with the DNA extraction services of the cell culture core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MOLECULAR BIOLOGY Principal Investigator & Institution: Chu, Mon-Li H.; Professor & Vice-Chair of Research; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The Molecular Biology Core serves two primary functions: 1. Establishing new and advanced technologies of molecular biology and implementing their use in Projects 1-5. 2. Providing a series of services to Projects 1-5, which is most efficiently and conveniently provided by a centralized facility. Relationship to the Program: This Core provides essential technologies to all of the Projects of the Program. The Core provides mutation analysis, genotyping, quantitative RT-PCR, and sizing and collection of DNA fragments by use of dHPLC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORNIFIED ENVELOPE PERMEABILITY BARRIER FUNCTION

ASSOCIATED

PROTEINS

AND

Principal Investigator & Institution: Elias, Peter M.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002 Summary: Although the role of structural proteins in the epidermal mechanical barrier is clear, their role in the permeability barrier is unknown. We hypothesize that selected structural and enzymatic proteins; i.e., those that are both regulated by Ca++ and associated with the cornified envelope (CE): involucrin, loricrin, transglutaminase 1 (TG1), pro-fillaggrin, and K1/10, are regulated/required for barrier homeostasis. This proposal will assess which of these proteins are regulated by permeability barrier requirements, and how these CE-associated proteins, in partnership with the lipid bound envelope (LBE) and the lipid-enriched extracellular lamellae, from the permeability barrier. Specifically, in Aim #1 we will determine which CE- associated proteins are regulated by altered barrier requirements, and whether Ca++ regulates

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their expression, by: a) measuring the time course of mRNA/protein expression for the CE-associated proteins after acute barrier disruption (acetone, tape stripping) and in essential fatty acid deficiency (EFAD) in hairless mice. b) Ascertaining whether changes in extracellular Ca++ (in vivo by sonophoresis and by immersion) modulate expression of the regulated CE protein(s); and the participation of the calcium receptor (CaR) and voltage-sensitive Ca++ channels in these changes. c) Determining whether the transient decrease in CE-associated protein expression facilitates barrier recovery. Using three transgenic over- expressing (involucrin, K6/16, and pro-filaggrin) murine models, and one of these proteins interferes with permeability barrier homeostasis and lamellar body secretion. In Aim #2, we will determine which CE-associated proteins are required for normal barrier homeostasis, and the mechanisms by which alterations in these proteins lead to barrier abnormalities, by: a) Assessing homeostasis in human and murine models with specific deletions or mutations of CE-associated proteins; i.e., in patients with lamellar ichthyosis (LI; TG1 deletion), epidermolytic hyperkeratoses (EHK;K1 or 10 mutation), ichethyosis bullosa of Siemens (IBS; K2e mutation), palmo-plantar keratoderma (NSPPK; K1 mutation), ichthyosis, Keratoderma (NSPPK; K1 mutation), ichthyosis vulgaris (pro-filaggrin deficiency), Vohwinkle's disease (loricrin mutation), plus involucrin and K10 murine knockout animals. b) Assessing the mechanisms whereby CE-associated proteins influence permeability barrier function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF GENE THERAPY FOR EPIDERMOLYSIS BULLOSA Principal Investigator & Institution: Yoon, Kyonggeun; Associate Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Gene targeting is designed to produce predefined alterations in the genome of eukaryotic cells. Advantage of gene targeting is that repaired gene can be maintained, expressed, and regulated as the normal endogenous gene and that it can rescue a dominant mutation. Viral gene replacement presents a problem of constitutive and unregulated expression of gene product even if such gene delivery is efficient to target cells. There are also safety concerns including immune reaction and generation of replication competent virus. An experimental strategy has been developed for a site-specific correction of single base mutations of target sequence by using an RNA-DNA oligonucleotide (RDO) (Yoon et al., 1996). Several characteristics of RDO make it attractive for in vivo application in epidermis. The accessibility of the tissue makes it possible to administer therapeutics locally, to monitor both the treated site and a control. We demonstrated the tyrosinase gene correction in melanocytes by RDO was inheritable in vitro (Alexeev and Yoon, 1998) and in vivo (Alexeev et al., 2000). During the course of in vivo study, we observed a surprisingly high level of genotypic correction from skin biopsy. We also found an increasing level of gene correction when skin biopsy was taken from older animals, suggesting that RDO is capable of epidermal stem cell gene conversion and that expansion of such cells may result in an apparent high level of gene conversion in epidermis. In this case, the high epidermal turnover may make the in vivo application RDO much more attractive than in vitro. Most murine models for genodermatoses with known genetic defects do not resemble the mutations found in human genetic diseases since they contain a large alteration of the mouse genome. Moreover, in some cases, they do not survive long enough to be useful because the entire body function is affected. In Aim 1, we plan to generate a dominant mutation found in several genes involved in cutaneous genetic diseases at localized area of

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murine skin by in vivo application of RDO. In Aim II, we plan to mutate the COL7A1 gene using the grafted human skin to SCID mouse by localized application of RDO. In Aim III, we plan to develop a new strategy of the targeted gene conversion using a single-stranded deoxyoligonucleotide, which is capable of correcting a single point mutation in mammalian cells, similar extent as RDO (Igoucheva et al., 2000). With this new finding, a relatively short oligodeoxynucleotide can be envisioned to make a sequence-specific change in the target sequence in mammalian cells. Emerging technologies of non-viral gene delivery methods, topical application, particle bombardment, and in vivo electroporation will be incorporated throughout the project. Therapeutic nucleic acid repair strategy will be useful not only generating an animal model for testing therapy modalities but also a potential clinical application of oligonucleotides to severely affected areas of genodermatoses patients for treatment. Furthermore, a capability to establish cells containing a specific alteration will provide valuable cellular models in skin biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPITHELIAL MATRIX IN CARCINOMA DEVELOPMENT Principal Investigator & Institution: Marinkovich, M Peter.; Assistant Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Overview: The important roles that epithelial matrix interactions play in tumor invasion and tissue morphogenesis are just beginning to be understood. Data generated through our efforts during the previous funding cycle suggest important roles for laminin 5, bone morphogenic protein (BMP 1) isozymes and alpha 6 beta 4 integrin in squamous cell carcinoma (SCC) progression and an important role for laminin 10 in basal cell carcinoma (BCC) development. The current studies are directed at further defining the role of the extracellular matrix in development of non melanoma skin cancers. Through synergistic collaboration with the other Projects, the ultimate application of these studies will be to discover new molecular approaches to inhibit carcinoma development. They propose to: 1. Determine the roles of laminin 5 and beta 4 integrin in SCC progression. This Aim will determine the mechanisms by which laminin 5 and beta 4 integrin impact upon SCC tumors. They hypothesize that laminin 5 may inhibit and b4 integrin may promote SCC progression. This aim will utilize a Ras driven turnorigenesis model where keratinocytes are engineered to form SCC like tumors in immunodeficient mice. The effects of site directed mutagenesis of key domains on laminin 5 and beta 4 integrin cDNA will be examined in vivo for effects on SCC progression by in vitro and in vivo assays of cell and tumor invasion. Tumor size, morphology, differentiation, apoptosis and adhesion to host stroma will be evaluated. 2. Demonstrate the function of BMP I isozymes in SCC progression. Their preliminary results showed that BMP 1 isozyme mediated processing of laminin 5 supported SCC tumor invasion in vitro and characterized a potent and specific BMP 1 inhibitor with potential tumor inhibitory effects. In this Aim, they seek to extend these results to in vivo models of SCC tumor development. Expression of each of the four BMP 1 isozymes and the processing of laminin 5 will be evaluated in a survey of SCC tumors. The effect of BMP 1 isozyme mediated laminin 5 processing on SCC tumor progression will be studied through overexpression studies. Finally, specific BMP 1 isozyme inhibitors will be evaluated in vivo for their effects on tumor invasion. 3. Discover how laminins impact upon BCC development. Laminins perform important roles in tissue morphogenesis as well as carcinoma development. Their preliminary results show an important role for laminin 10 in hair development and suggest that

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Epidermolysis Bullosa

laminin 10 supports BCC development as well. Additional studies suggest that laminin 5 may have an inhibitory effect on BCC. They will evaluate a number of tumor parameters in the study of the effects of laminin 10 inhibition in a BCC animal model. Multiple approaches will be utilized including the use of inhibitory antibodies and the use of laminin 5 mice. They will assess the effects of laminin 5 overexpression and underexpression on BCC development in an animal model using laminin 5 cDNAs delivered to primary and laminin 5 null EB keratinocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIBROGENIC FACTORS IN OCULAR CICATRICIAL PEMPHIGOID Principal Investigator & Institution: Ahmed, Razzaque A.; Associate Professor; Oral Medicine and Infection Immunity; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term objective of this grant application is to study the molecular mechanism of scarring in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Severe conjunctival scarring leads to blindness in about 25% of OCP patients, inspite of aggressive systemic therapy. The aim of this grant proposal is to identify some of the factors that are involved in the inflammatory and fibrotic stages, and define their role in the scarring process. Investigators studying ocular scarring in toxic epidermolysis necrosis, Steven-Johnson syndrome, epidermolysis bullosa acquisita, and other similar diseases will significantly benefit from these experiments. The PI has focused on only few molecules in an attempt to define a model system. Our preliminary studies suggest an important role for macrophage colony-stimulating factor (m-CSF), transforming growth factor (TGF)beta1, matrix metalloproteases (MMPs), and tissue inhibitors of metalloproteases (TIMPs) in regulating inflammatory and fibrotic events in the conjunctiva of OCP patients, and in fibroblasts isolated from conjunctiva of OCP patients. In our proposed study, we will determine the role of macrophage-recruiting molecules, isoforms of TGFbeta, connective tissue growth factor (CTFG), specific members of MMPs and TIMPs (as determined by our microarray analysis) in conjunctiva of patients with OCP. We will perform in vivo studies using an established mouse model of conjunctival scarring to determine the effects of blocking CTGF in this model. We anticipate that the results from studies proposed in this grant application will provide information that will identify and describe some of the key molecules that influence conjunctival scarring in patients with OCP. The studies have significant therapeutic potential. The identified molecules or portion of processes that mediate could be blocked or arrested, and this may result in cessation of disease progression and, prevention of blindness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE EXPRESSION AND DIFFERENTIATION IN HUMAN EPIDERMIS Principal Investigator & Institution: Fuchs, Elaine V.; Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-DEC-1980; Project End 31-MAY-2002 Summary: Our objective is to understand the function of intermediate filament (IF) proteins and their differential expression in tissues. The epidermis has been chosen as a model system, since it is possible to (l) culture human epidermal cells under conditions where differentiative properties are retained; (2) use keratinocyte-specific promoters to

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target expression of foreign genes to the epidermis of transgenic mice; and (3) biopsy skin from transgenic or embryonic stem (ES) cell-derived mice, enabling extensive analyses prior to breeding. Keratins are the major structural proteins of epidermis. They belong to the IF superfamily, composing extensive 10 nm cytoskeletal frameworks in cells. As basal cells terminally differentiate, they switch from expression of keratins KS & K14, to K1 & K10. Palmar/plantar epidermis expresses an additional suprabasal keratin, K9. We have characterized many of the human epidermal keratin genes and used molecular genetics to identify amino acids involved in 10 nm filament assembly. We showed that transgenic mice expressing IF assembly-perturbing 14 or K10 mutants exhibit phenotypes similar to the blistering skin disorders, Epidermolysis Bullosa Simplex (EBS) or Epidermolytic Hyperkeratosis (EH), respectively. Subsequently, we discovered point mutations in the K14/K5 (EBS) and K1/K10 (EH) genes of human patients, thereby revealing the genetic bases for these two autosomal dominant diseases. Additional sequence analyses of EBS and EH families are now required to ascertain whether these diseases always involve keratin mutations, and whether locations of mutations within keratin polypeptides correlate with disease severity. Functional analyses should elucidate whether the degree to which a mutation perturbs filament assembly correlates with disease severity. Similar strategies should unravel whether K9 mutations are involved in Epidermolytic Palmoplantar Keratoderma. Collectively, these studies are of fundamental importance to understanding the relation between keratin gene defects and this group of blistering human disorders. They are essential in developing new and improved diagnostic tools for these diseases. While dominant negative keratin mutations in mice led to a genetic understanding of EBS and EH, they have not allowed unequivocal assessment of keratin function and the significance of IF multiplicity. Thus, we do not know (l) whether cell degeneration and seemingly binucleate cells arise from absence of an IF network or accumulation of altered cytoskeletal material, nor (2) whether IF diversity is redundant or whether it enables a cell to structurally tailor its cytoskeleton to suit its particular needs. To answer these questions, homologous recombination and ES technology are needed to knock- out, mutate and replace endogenous epidermal keratin networks in vivo. An understanding of keratin function and the significance of IF diversity is of utmost importance for elucidating the consequences of IF defects in human disease. This work will be essential to the development of new and improved methods to treat disorders of IF proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY FOR DYSTROPHIC EPIDERMOLYSIS BULLOSA Principal Investigator & Institution: Chen, Mei; Professor; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2005 Summary: Dystrophic epidermolysis bullosa (DEB) is an incurable, inherited mechanobullous disease of the skin characterized by skin fragility, blister formation, and chronic wounds. DEB is caused by defects in the human gene encoding type VII collagen. Type VII collagen is the main component of anchoring fibrils, structures within the basement membrane of skin which are attenuated, diminutive, or absent in DEB. These structures are thought to anchor the epidermis to the dermis, and their paucity in DEB results in the skin features. Gene therapy is considerated one strategy to correct this defect. The long-term objective of this proposal is to develop an ex vivo gene therapy strategy for DEB. We propose the targeted introduction of a transgene coding for type VII collagen into cultured keratinocytes and fibroblasts from DEB patients, cells that cannot endogenously make this protein. The "gene corrected" cell cultures would then be

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transplanted onto the patients as an autograft. We have constructed both of full-length type VII collagen and a truncated type VII minicollagen plasmid expression vectors and purified large quantities of the recombinant proteins from stably transfected human cells. The minicollagen although truncated retains all the functional properties of a fulllength alpha chain. Using a retroviral-mediated expression vector, we have induced RDEB keratinocytes to express the minicollagen which reversed the RDEB cellular phenotype to that of normal keratincytes. In this proposal, we will build upon this work and develop highly efficient viral vectors that will allow sustained and targeted type VII collagen transgene delivery into human keratinocytes and fibroblasts. We will generate new minigene and full length type VII collagen delivery vehicles using lentiviral vectors which can offer high efficiency, sustained transgene expression and the ability to transduce nondividing cells and can accommodate the 9 kb full-length type VII collagen Cdna. We will also use vectors with cellular promoters, such as the K14 promoter, to promote sustained expression and target the basal keratinocytes. Using our wellestablished assays, we will examine the phenotype and cellular functions of "genecorrected" RDEB cells. Lastly, we will advance from our monolayer keratinocyte and fibroblast cultures to a three dimensional, composite, skin- equivalent, organotypic culture model with diseased and "gene corrected" RDEB cells. These cultures will also be grafted onto SCID mice and evaluated for anchoring fibril formation and sustained expression of the transgenes for type VII collagen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE THERAPY MODEL FOR DYSTROPHIC EPIDERMOLYSIS BULLOSA Principal Investigator & Institution: Cserhalmi-Friedman, Peter B.; Dermatology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 20-APR-2001; Project End 28-FEB-2005 Summary: (Taken from the application): The dominantly inherited form of dystrophic epidermolysis bullosa (DDEB), a mechanobullous disease which presents with blister formation in the skin, is the result of dominant negative mutations in the type VII collagen gene (COL7Al). These mutations cause conformational changes in type VII collagen that interfere with the proper assembly of anchoring fibrils, important attachment structures of the cutaneous basement membrane zone. Currently, there is no available treatment option nor applicable in vitro experimental model for DDEB. The aim of the proposed research is to evaluate the feasibility of a novel treatment option, utilizing hammerhead ribozymes and deoxyribozymes for the targeted ablation of mutant COL7AI mRNA. Hammerhead ribozymes and deoxyribozymes targeting mutant COL7A1 mRNA will be designed, manufactured and tested utilizing already established methodology. We will engineer a three-dimensional skin model using human dermal fibroblasts and immortalized DDEB patient keratinocytes that will form a cutaneous basement membrane with the characteristics of DDEB. This model will serve as in vitro system to test the proposed novel treatment strategy for DDEB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE THERAPY MODEL OF DYSTROPHIC EPIDERMOLYSIS BULLOSA Principal Investigator & Institution: Christiano, Angela M.; Associate Professor; Dermatology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-SEP-1995; Project End 30-JUN-2006

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Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENOTYPE CORRELATES AND CLINICAL TRIALS IN INHERITED EB Principal Investigator & Institution: Fine, Jo-David R.; Professor; Dermatology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 01-AUG-2002 Summary: Inherited epidermolysis bullosa (EB) encompasses those diseases characterized by mechanically fragile skin and the tendency for blister formation. As of May 1998, four major types, at least 23 phenotypically distinctive subtypes, and at least 200 different genotypes have been described. Now that over 3,000 clinically well characterized patients with EB have been assembled via the National EB Registry, we propose to use the Registry, and the mechanism of a K24 Award, to attempt to address several clinically relevant and timely issues, to include (1) phenotype - genotype correlations across both major and minor types and subtypes of inherited EB, and the identification of those genotypes which have specific prognostic or therapeutic significance., (2) initiation of a prospective interventional clinical trial to assess the possible beneficial role of isotretinoin or another systemic retinoid as a chemopreventive agent against the development of additional squamous cell carcinomas in those patients with RDEB-HS who have developed at least one such tumor; (3) initiation of one or more other clinical trials to determine the benefit, if any, in the performance of selected medical or surgical interventions in groups of patients having more severe forms of EB, to include (a) early elective gastrostomy placement, (b) hand splinting, (c) use of one or more topical cytokine preparations and/or newer wound, healing dressings, (d) the use of topical or systemic antioxidant agents, and (e) aggressive nutritional supplementation; and (4) characterization of baseline metabolic and nutritional parameters in patients with severe generalized forms of inherited EB. It is hoped that the results of these several proposed clinical studies will provide new insights into the management of patients with EB, as well as provide an excellent means whereby young investigators interested in patient-oriented research can be mentored and trained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GORDON RESEARCH CONFERENCE ON BASEMENT MEMBRANES Principal Investigator & Institution: Kramer, James M.; Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 028920984 Timing: Fiscal Year 2002; Project Start 09-JUN-2002; Project End 31-DEC-2002 Summary: (provided by applicant): This application requests partial funding for the support of invited speakers for the 2002 Gordon Conference on Basement Membranes. This is the eleventh in a series of conferences, which have become an international forum for dissemination of new ideas and information about the structure and functions of basement membranes (BMs). These are complex, three dimensional, extracellular structures formed at epithelial mesenchymal interfaces and around mesenchymal cells, with important roles in the organization and function of most tissues and organs, e.g., blood vessels, lung, kidney, skin, peripheral nerves, and muscle. For example, basement membranes regulate the migration and organization of cells in the musculoskeletal system, as well as axons and synapses in the nervous system. Mutations in genes encoding basement membrane components result in severe inherited disorders in

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humans (e.g., epidermolysis bullosa of skin, congenital muscular dystrophy and associated nerve defects, Alport syndrome of kidney). Acquired defects in basement membranes also contribute to the pathogenesis of diabetic microvascular disease and serve as entry sites for infectious agents, such as leprosy, and for metastatic cancer cells. Traditionally, the conference has attracted scientists from a wide range of fields in basic research, including protein and carbohydrate structure, gene expression, cell and developmental biology, and neurobiology. In addition, it has been attended by clinicians and scientists involved in research and/or treatment of human disorders involving BM components of lung, blood vessels, skin, kidney, bone, muscle and immune systems. Basic studies of BM degradation and turnover are also of interest to scientists investigating dynamic processes such as angiogenesis, cancer metastasis, embryo implantation, and involution of the mammary gland and uterus. There has been substantial interest from clinicians and scientists in the pharmaceutical and biotechnology industries studying the roles of BMs in wound healing, angiogenesis, nerve regeneration, inflammation, and tissue repair. The Conference will present a diverse mixture of sessions on the basic science of basement membrane and extracellular matrix (ECM) structure, biosynthesis, assembly, turnover, and functions. Comparative studies of BM function in vertebrates and invertebrates and the roles of BM and ECM in embryonic development will also be incorporated into the program. In addition, emphasis will be given to studies on the genetic analyses of BM and ECM functions, and the generation of animal models of human BM disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMIDESMOSOMES IN BULLOUS PEMPHIGOID Principal Investigator & Institution: Giudice, George J.; Associate Professor; Dermatology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2004 Summary: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by the production of autoantibodies that react with components of the hemidesmosome, an adhesion-related organelle of basal epidermal keratinocytes. Studies supported by this grant utilized patient autoantibodies as specific probes to facilitate the molecular cloning and characterization of BP180, a major antigen associated with these autoimmune diseases. BP180 was shown to be a type II transmembrane protein with a long C-terminal collagenous domain that projects into the extracellular region beneath the epidermal hemidesmosome. The first specific aim of the current grant application addresses important questions regarding the structure of both the intracellular and extracellular domains of the BP180 protein. In the execution of these studies, high levels of recombinant forms of BP180 will be expressed in cultured mammalian cells using an Epstein Barr Virus-based vector, pCEP4. Using this system, the applicants recently demonstrated that the BP180 ectodomain is capable of forming a homotrimeric complex, with a molecular shape and flexibility properties consistent with their structural model of BP180 in which the ectodomain comprises a series of articulated, rigid rod-like structures. A part of this aim, they plan to define the protein segments that are essential for the assembly of the BP180 trimer, and to investigate the structural consequences of BP180 mutations that are known to be associated with inherited disorders of the basement membrane zone. Questions related to the function of BP180 will be addressed in specific aim 2. To further test their hypothesis that BP180 functions in cell-matrix attachment, they plan to extend their recent studies in which wild type BP180 was transfected into BP180-deficient keratinocytes from patients with generalized atrophic benign epidermolysis bullosa (GABEB). The GABEB keratinocytes and other cultured

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cells transfected with wild type and mutant BP180 expression constructs will be assayed for alterations in hemidesmosome assembly and/or cell matrix attachment properties. In addition, a variety of approaches will be employed to identify the extracellular BP180 ligand(s) and to determine whether ligand binding is coupled with the transduction of a signal across the membrane. In specific aim 3, the BP180 ectodomain will be further analyzed as the target of lgG and IgA class autoantibodies associated with several subepithelial blistering diseases such as cicatricial pemphigoid and linear IgA bullous dermatosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LAMININ ANGIOGENESIS

8

&

LAMININ

10

IN

CUTANEOUS

WOUND

Principal Investigator & Institution: Li, Jie; Dermatology and Cutaneous Surgery; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2004; Project Start 15-MAR-2004; Project End 28-FEB-2007 Summary: (provided by applicant): Laminins are major components of the extracellular matrix and influence a variety of important biological processes including cell attachment, migration, angiogenesis, and wound healing and tissue development. The biomedical importance of laminins is best illustrated by human severe blistering disease, epidermolysis bullosa, due to the deficiency of laminin 5 and subsequent failure of wound repair. It has been recently found that two newly identified laminins, 8 (alpha4beta1gamma1) and 10 (alpha5beta1gamma1), are the major laminins produced by human dermal-microvascular endothelial cells (HDMECs). They likely play important roles in endothelial cell attachment, spreading and angiogenesis. Our longrange goal is to improve the therapeutic outcomes of wound healing. The objective of this application is to determine the roles of the Iaminins 8 and 10 in wound angiogenesis. In this study, I propose two specific aims: 1. To determine the functions of laminin 8 and laminin 10 in endothelial cell attachment and migration. Cell attachment and migration are two essential and tightly linked processes in wound angiogenesis. The ability of these two molecules to promote cell attachment and migration of HDMECs and the cell surface receptors responsible for these interactions will be determined using methods of cell binding and migration assays in vitro. 2. To determine the roles of laminins 8 and 10 in endothelial basement membrane assembly and capillary tubule formation during wound healing. An in vitro model of endothelial basement membrane formation/capillary tubule formation, and an in vivo system of human angiogenesis model will be utilized to determine the significance of laminin 8 and laminin 10 in angiogenesis and granulation tissue formation during wound repair. We expect to obtain basic functional information about the cell- and ligand-binding properties of laminins8 and 10, and to demonstrate that these two laminins play important roles in one or more key steps of wound angiogenesis, including endothelial cell attachment, migration, basement membrane assembly and microvascular blood vessel formation. In addition, the studies are expected to have profound implications on the development of novel therapies directed at laminin components to improve angiogenesis and wound healing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATRIX PROTEIN IN HUMAN EPIDERMAL NEOPLASIA Principal Investigator & Institution: Kimmel, Robin A.; Biological Sciences; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The epidermis is the site of the first and second most common cancers in the U.S., basal cell carcinoma and squamous cell carcinoma (SCC). Human tumor samples and mouse models of SCC induction show a correlation between upregulation of basement membrane proteins and tumor progression. The medical relevance of murine studies of SCC, however, is limited by major differences between mouse and human skin and by greater ease of transformation of murine tissues. While the importance of cell-matrix interactions in tumor initiation and growth is wellappreciated, no studies have yet addressed the need for specific stromal elements and their cellular receptors in this process. Their our lab's recent evidence that integrin and its ligand laminin 5 are required for SCC development implies that hemidesmosomemediated adhesion may potentiate tumorigenesis. The overall goal of this proposal is to determine the role of specific epidermal matrix components in promoting human epidermal tumor formation. First, the roles of Type XVII collagen (BP180, BPAG2) and Type VII collagen, which interact with integrin alpha6beta4 and laminin 5, will be examined. Primary keratinocytes deficient in collagen XVII and collagen VII from patients with the inherited skin disease epidermolysis bullosa (EB) will be used to assess the tumor formation potential of deficient cells as compared to cells with restored protein expression. Corrected and uncorrected cells will be transduced with Ras and other retrovectors and assayed for their ability to support subcutaneous tumor growth. Additional studies will assess the effect of laminin 5 ablation on the continued growth of epidermal tumors. Laminin 5 blocking antibodies will be tested for their ability to inhibit growth of established Ras-induced tumors. Furthermore, a genetic approach will be used in which Cre recombinase inducibly removes retrovirally restored laminin 5 eDNA from EB cells within a growing Ras-induced epidermal tumor. These studies provide an initial evaluation of matrix components involved in the establishment and growth of tumors. Subsequent explorations that include delineation of specific functional domains within the matrix proteins found to enhance tumor growth may provide potential targets for therapeutic interference with SCC progression. At the end of the funding period, they hope to have defined the functional importance of epidermal matrix components in invasive human epidermal neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR THERAPEUTICS FOR EPITHELIAL DISORDERS Principal Investigator & Institution: Khavari, Paul A.; Associate Professor; Dermatology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 30-JUN-2007 Summary: (provided by applicant): Within the framework of the original Program Project application consisting of 3 projects and 3 cores, progress was made during the past four years in cutaneous basement membrane zone (BMZ) studies and in developing ex vivo gene therapy for epidermolysis bullosa (EB). BMZ studies have helped to elucidate the role of BMZ proteins in epidermal adhesion, healing, cell migration, neoplasia and EB. Ex vivo gene therapy efforts have also met with some success and provide the basis for human clinical trials now being initiated in EB. This progress has laid the foundation for efforts to develop the next level of advances in molecular therapeutics for direct administration to skin in the context of further biological studies directed at epidermal BMZ biology and carcinogenesis. This focus on direct tissue delivery is designed to generate more practical therapeutic technology platforms for future application in humans. The specific goals of this research proposal are 1) to develop new approaches for delivery of gene and protein-based molecular therapeutics

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to skin, 2) to define further the mechanistic basis for BMZ changes in epidermal neoplasia and to identify targets for its regulation, 3) to characterize and develop a new general approach for molecular therapy to epithelium via non viral integrating vectors and 4) to characterize signaling pathway elements in epidermal carcinogenesis and identify therapeutic targets for their disruption. The specific projects are as follows: 1. Delivery of Molecular Therapeutics to Skin (P.A. Khavari)2. Epithelial Matrix as a Target for Molecular Therapy (M.P. Marinkovich) 3. Transposon Based Gene Therapeutics (M.A. Kay)4. Signaling and Therapeutic Targeting in Epidermal Neoplasia (A.E. Oro) The central objective of this proposal, framed within the context of increasing insight into epidermal BMZ function in genodermatoses and neoplasia, is the development of new molecular therapeutic approaches for 2 representative diseases affecting these processes, epidermolysis bullosa and epidermal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS FOR GENE THERAPY AND JUNCTIONAL EB Principal Investigator & Institution: Pulkkinen, Leena; Dermatology/Cutaneous Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 23-NOV-2002 Summary: The overall goal of this project is to develop conventional and conditional mouse models for junctional epidermolysis bullosa (JEB) by disrupting or affecting the expression of the gamma2 chain gene (LAMC2) of laminin 5 using Cre/loxP and FLP/frt targeting systems. These mice are used as tools towards development of therapy for JEB. Towards the overall goal of this project, the following specific aims are proposed: 1) Isolation and characterization of LAMC2 lambda-clones from mouse genomic library; 2) Construction of the targeting vector based on the data obtained from 1); 3) Generation of three allelic mouse models with different JEB phenotypes by targeting the LAMC2 gene; 4) Development of ex vivo and in vivo gene therapy protocols. Junctional epidermolysis (JEB) bullosa is a recessively inherited form of EB characterized by cutaneous and extracutaneous manifestations. There are no specific therapies available for any type of EB thus far. To achieve the specific aims of this proposal, the genomic LAMC2 clones will be isolated and characterized. This information provides basis for construction of targeting vector, which is then used for generation of three allelic mouse models utilizing Cre/loxP and FLP/frt systems. One of the models will be a conditional, tissue-specific knockout for frameshift deletion of exon 8. In this mouse the deletion of exon 8 is activated by Cre expression driven under K5 promoter. The phenotype of this mouse is expected to be milder than that of the corresponding conventional knockout mouse with the same deletion which will be developed as the second model of JEB. The third mouse model is created by FLP/frt system to target in-frame deletion of exon9. These mouse models will be used in this proposal for development of technology towards targeted correction of the mutation. For this purpose, a specific targeting vector containing the mutant region, or BAC and P1 clones containing full-length LAMC2 gene will be delivered by electroporation together with FLP protein into the cultured keratinocytes, or directly onto the skin of affected mouse. These genomic clones, fitted with frt sites, are expected to insert into the frt site present in the mouse genome created during manipulation of the mouse. The engineered cells, grafted back to the skin of the mouse, are expected to restore LAMC2 and laminin 5 expression as well as improve the skin phenotype. The development of these mouse models provides information on the different tissue involvement in the

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pathogenesis and the severity of the JEB. These mice will serve as tools for development of novel gene therapy protocols for JEB in future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MODELS OF EPIDERMOLYSIS BULLOSA Principal Investigator & Institution: Klement, John F.; Assistant Professor; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: ABSTRACT NOT PROVIDED Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEMPHIGUS AND PEMPHIGOID Principal Investigator & Institution: Diaz, Luis A.; Professor and Chairman; Dermatology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 28-FEB-2006 Summary: This application represents the competitive continuation of the Merit Award R37-AR32081 that is funded until June 20, 2000. During the last 10 years of funding we have completed several relevant studies on pemphigus vulgaris (PV), non-endemic pemphigus foliaceus (PF), endemic PF [also known as Fogo Selvagem (FS)] and Bullous Pemphigoid (BP) that are summarized as follows: a) we have developed animals models of PV , PF, and FS by passive transfer of patients' IgG, b) we have developed affinitychromatography procedures to purify autoantibodies from PF, PV, and BP sera, c) we have developed a highly sensitive and specific ELISA to detect PF, PV, and BP autoantibodies using recombinant proteins, d) we have characterized a human settlement with a high prevalence of endemic FS (3 percent) in a Brazilian Indian Reservation, e) we have studied in this reservation 5 FS cases in the pre-clinical stage and several normal controls that exhibit moderate titers of anti-dsg1 IgG autoantibodies, predominantly IgG1. These autoantibodies increased several fold when FS was fully established, and the predominant IgG isotype was IgG4, f) we have been able to clone antigen-specific T cells from peripheral blood of FS patients from this Indian reservation. In addition, g) we mapped the hemidesmosome as the target of BP autoantibodies, h) we discovered and characterized the BP180 antigen as a component of hemidesmosomes, i) we developed the first animal model of BP by passive transfer of anti-BP antibodies. In this grant we hypothesize that in FS anti-dsg1 autoantibodies of the IgG1 and IgG4 subclass may differ in their pathogenicity and epitope-specificity. To test this hypothesis we will isolate and study dsg1-specific IgG1 and IgG4 from FS sera, clone and sequence V genes from B cells of these patients by single cell RT-PCR, develop monoclonal anti-idiotypic antibodies, generate recombinant anti-dsg1 Fabs, and carry out dsg1 epitope mapping studies. Similar studies will be performed with anti-dsg3 autoantibodies in PV. These studies may lead to new therapies for these serious cutaneous autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGRAM PROJECT GRANT Principal Investigator & Institution: Uitto, Jouni J.; Professor and Chair; Dermatology/Cutaneous Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587

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Timing: Fiscal Year 2002; Project Start 15-AUG-1987; Project End 31-MAR-2007 Summary: This renewal application proposes extensive and innovative studies focusing on the molecular genetics of the cutaneous basement membrane zone (BMZ) towards delineating the molecular basis of various forms of epidermolysis bullosa (EB) and other selected genodermatoses affecting the epidermis. The proposed studies are designed to test the hypothesis that genetic lesions in structural genes expressed in the epidermis underlie variants of these diseases, and that the precise phenotype and mode of inheritance depend on the types and combinations of specific mutations in distinct genes. This application is based on solid progress in this project, including (a) expansion of the molecular basis of the recessive dystrophic forms of EB allowing refinement of genotype/phenotype correlations; (b) identification of novel and de novo COL7A1 mutations in dominant DEB, with an impact on genetic counseling of the families at risk of recurrence; (c) identification of a large number of novel and recurrent mutations both Herlitz and non-Herlitz junctional EB; (d) identification of uniparental disomy of chromosome 1 as a novel mechanism for H-JEB; (e) demonstration in mutations in the genes ITGA6 and ITGB4 encoding alpha-6-beta-4 integrins subunit polypeptides in EB with pyloric atresia,; (f) cloning of the human plectin gene and demonstration of mutations in EB with late-onset muscular dystrophy; (g) cloning of mouse type VII collagen and desmoglein 3 genes with development of "knock-out" mice with blistering phenotype; (h) identification and characterization of several novel genes expressed into the epidermis, including periplakin, ladinin, and desmo-15; (i) refinement of RNADNA chimeric oligonucleotide technology for repair of the mutated genes in heritable skin diseases. This proposal details continuation of concentrated, multi-disciplinary studies in five highly interdependent projects: Project 1, "Molecular Genetics of EB and Other Heritable Disorders of the Cutaneous BMZ and Epidermis," will provide precise information on the specific mutations in the gene/protein system that are at fault in various forms of EB and other epidermal heritable disorders. Project 2, "Identification and Characterization of Candidate Genes/Protein Systems Expressed in the Skin," will provide new gene probes and information about novel genes as potential candidate genes for epidermal genodermatoses. Project 3, "Consequences of the Mutations at the Protein Structure/Function Level" will examine the structural and functional alterations that result from distinct mutations in the candidate genes, utilizing computer modeling and monitoring functional interactions in biosensor analysis system. Project 4, "Development and Testing of Animal Models for EB," will generate novel animal models for EB. Project 5, "Development of Non-Viral Gene Therapy for Cutaneous Diseases," will concentrate on testing gene therapy approaches utilizing RNA/DNA chimeric oligonucleotide strategies. These multidisciplinary studies are expected to provide precise information of critical importance for translational applications towards development of refined classification, genotype/phenotype correlations, basis for genetic counseling, and prenatal testing, as well as providing the basis for novel gene therapy approaches for this devastating group of skin diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PURIFICATION OF EPIDERMOLYSIS BULLOSA ANTIGEN Principal Investigator & Institution: Woodley, David T.; Professor and Chief; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-MAR-1990; Project End 30-JUN-2008 Summary: (provided by applicant): Anchoring fibrils, composed of type VII collagen, are a critical factor in epidermal-dermal adherence. Both genetic and autoimmune disorders targeting type VII collagen result in chronic, debilitating blistering diseases of

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the skin. Dystrophic Epidermolysis Bullosa (DEB) is due to mutations in COL7A1, the gene that encodes for type VII collagen. It may be inherited in a dominant or recessive (RDEB) pattern and is incurable and often lethal. An acquired form of DEB, epidermolysis bullosa acquisita (EBA), is caused by IgG autoantibodies targeted against type VII collagen which results in perturbed, poorly functioning anchoring fibrils. Our overall goal is to understand the structure and function of type VII collagen and anchoring fibrils as they pertain to epidermal-dermal adherence and DEB. Traditional biochemical methods were unable to provide enough purified type VII collagen to facilitate this work. During our last funding cycle, we resolved this problem using a molecular biology approach and can now make milligram quantities of purified type VII collagen and various domains and sub-domains of the molecule. Using rigorous parameters, we have shown that the recombinant molecule is identical to the authentic molecule. Using 293 cells or RDEB cell lines that cannot make collagen VII, we can transfect wild type COL7A1 or any published DEB mutation into these cells and create type VII collagen molecules that reflect a given DEB gene defect. Likewise, we can create DEB cells that reflect the biology of cells from patients suffering from DEB. We also have an in vivo human skin equivalent model to examine the quantity and quality of anchoring fibrils in designer skin equivalents made from normal skin cells, RDEB wild type cells, gene-corrected cells or designed gene-defective cells. We also developed a new murine model for EBA using euthymic SKH1 hairless mice. In this proposal, using these reagents and methods, we will study the structure and function of wild type and DEB type VII collagen molecules including matrix and cell binding sites, exportation from their cell of origin, resistance to protease, triple helix and anti-parallel dimer formation, disulfide bonding and formation of in vivo anchoring fibrils. We will create RDEB cells harboring 10 COL7A1 mutations known to result in the production of an abnormal type VII collagen alpha chain protein. We will examine the cellular biology of designer DEB cells in terms of morphology, proliferation, matrix attachment and motility. We will examine the biology of our newly developed EBA animal model. By immunoabsorption of anti-type VII collagen antibodies against domains and subdomains of type VII collagen, we will determine the pathogenic EBA epitopes on type VII collagen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REMODELIN, A NOVEL VASCULAR INJURY AND BONE RELATED GENE Principal Investigator & Institution: Lindner, Volkhard; Adjunct Professor; Maine Medical Center 22 Bramhall St Portland, Me 04102 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): With the intention of identifying novel genes involved in the arterial response to injury we undertook a differential screen of genes expressed in normal and injured arteries. We identified a novel sequence that with the exception of bone was not expressed in normal tissues, but highly induced in injured arteries. This cDNA contained an open reading frame of 245 amino acids with no significant homology to any known protein with the exception of a 36 amino acid (aa) long domain with 59% homology to the helical repeat regions found in collagens. Comparison with the human cDNA revealed 98% identity at the amino acid level indicative of a highly conserved protein. Northern blotting of mRNA derived from various adult rat organs revealed significant levels of this mRNA only in bone and lung. In balloon-injured arteries expression of this mRNA was prominent in adventitial fibroblasts during the proliferative and remodeling phase and only little expression was

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seen in smooth muscle cells of the developing neointima. Bone showed expression in the matrix of resting, proliferating and hypertrophic chondrocytes but expression was lost from the matrix as chondrocytes reached the apoptotic zone of the growth plate. Expression was also observed in periosteal cells. Based on its expression pattern, we named the gene remodelin. Several findings indicate that remode!in has important biological functions particularly in the arterial response to injury as well as in bone and cartilage matrix formation. These include: 1) increased remodulin expression in vitro is associated with decreased TGF-Beta expression as well as reduced TGF-Beta dependent gene expression (collagens type I and III), 2) increased remodulin expression in vivo results in phenotypes reminiscent of collagen mutants found in osteogenesis imperlecta (01), dystrophic epidermolysis bultosa (DEB) and myopathies (Bethlem), 3) in the absence of remodelin, expression of bone differentiation markers such as osteopontin and alkaline phosphatase (ALP) are dramatically increased, and 4) inhibition of Cbfa1 dependent gene expression such as osteocalcin by remodeiin. As such, remodelin appears to be an in vivo regulator of skeletal tissues and wound healing responses, potentially influencing calcification and differentiation along the chondrocyte/osteoblast lineages. As a potential inhibitor of calcification in the vessel wall this proposal will examine the role of remodelin in vascular calcification and remodeling using both in vitro and in vivo approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF TRIPLE-HELICAL PROTEINS Principal Investigator & Institution: Brodsky, Barbara M.; Professor; Biochemistry; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2003; Project Start 01-MAR-1977; Project End 31-AUG-2007 Summary: A peptide approach to a comprehensive understanding of the effect of amino acid sequence (Gly-X-Y)n on the stability, conformation, folding, dynamics and selfassociation of the normal and mutant collagen triple-helix is in progress. Our goals are to complete sequence-stability correlations at the molecular level; to develop peptides to model triple-helix self-association; and to pursue the disruption caused by Gly substitutions found in collagen diseases. Previous host-guest peptide studies established the triple-helix propensities of all 20 amino acids for the X and Y positions, and evaluation of molecular interactions within the triple-helix will be completed. These relationships between Gly-X-Y sequence and stability will be used to formulate predictions for the global stability of collagen model peptides and to relate local stability variations along collagen with ligand binding sites, microunfolding implicated in fibril formation, and the clinical severity of mutations. Calorimetric investigations are proposed to elaborate the mechanism of hydroxyproline stabilization of the triple-helix, and studies are proposed to further investigate the recently established sequence related modulation of triple-helix twist. An important goal is to establish a peptide system to model the self-association of triple-helices, since collagens function in supramolecular assemblies and some collagen mutations are pathological because of their influence on higher order structure. Strategies to design self-associating peptides will include pairs of oppositely charged residues to promote in register arrays and adaptation of sticky end and repeating pattern designs to form staggered arrays. Studies are proposed on peptide models of type I collagen mutations leading to a bone disease (osteogenesis imperfecta) and of type VII collagen mutations leading to a blistering skin disease (dystrophoic form of epidermolysis bullosa). The effect of the immediate sequence environment of the mutation and the identity of the residue replacing the Gly will be

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examined. Placing collagen structure, dynamics, and folding in a solid physicochemical framework through peptide studies will provide a context for understanding normal biological activities of selfassociation and binding, and for the changes occurring in many diseases affected by this abundant protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE OF INTEGRINS AND YWTD BETA PROPELLER DOMAINS Principal Investigator & Institution: Springer, Timothy A.; Professor; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Integrins are functionally and structurally complex surface molecules involved in multiple aspects of vascular function including development, thrombosis, and inflammation. Current understanding and future work on integrins would be enormously advanced by a three-dimensional structure of a representative integrin. Integrins are large heterodimers, and therefore it is logical to both attempt to the structure of intact heterodimers, and modular units. Approaches are presented to optimize obtaining crystallizable heterodimers or truncated heterodimer fragments. Genetically engineered extracellular por5tions of integrin alpha/beta heterodimers, either complexed with ligand or not, will be designed, produced, crystallized, and subjected to structural determination. Work is piloted with the alpha5beta1 integrin; backup integrins that are low in glycosylation and have multiple ligands or few conformation states are alphaIIbbeta3 and alpha6beta4. Integrins will be stabilized in a single conformation state. High level secretion is obtained by fusion to disulfide-liked coiled-coils. Minimized heterodimers are already produced that bind ligand. These and other fragments are used to explore integrin function. In parallel, work is under way on previously and newly defined modular units within integrins. Beta subunit fragments to be tested include an internal deletion of the I-like domain that already yields crystals; integrin EGF domains that already yield NMR data; and Pactolus, a beta subunit homologue that does not associate with an alpha subunit and lacks a specificitydetermining loop. The work on integrins will also be illuminated by work on structurally and functionally related domains, e.g. beta-propeller domains in nidogen or bacteria, that may be more easily isolated as modules and solved structurally. A putative cyanobacterial beta-propeller has sequence homology to the putative integrin beta-propeller domain in the extracellular protein nidogen, in complex with a fragment of its ligand laminin, will be structurally determined. A related YVTD module in a bacterial protein has already yielded atomic resolution diffraction. The long-term goal of this project is to define the ligand binding sites in integrins, how alpha and beta subunit modules come together in the head piece to bind ligand how the alpha and beta subunit stalk regions interact with one another to regulate ligand binding, and how the ligandbinding head piece modules interact with one another and with stalk modules to transduce signals from within the cell that modulate ligand binding, and to transduce signals from ligand binding into the cell. The molecular pathologies of Glanzmann's thrombasthenia and epidermolysis bullosa will be defined. Binding site structures will advance the development of drugs that antagonize integrins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TESTING GENE THERAPY FOR EPIDERMOLYSIS BULLOSA SIMPLEX Principal Investigator & Institution: Roop, Dennis; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The Dowling-Meara variant of epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease inherited in an autosomaldominant fashion. Besides symptomatic care, no effective therapeutic treatment is available for EBS. Therefore, gene therapy is the only option for a permanent corrective therapy for these patients. Prior to testing gene therapy approaches for EBS in humans, it is desirable to utilize a pre-clinical animal model to determine the safety and efficacy of these approaches. We have recently generated a transgenic mouse model that mimics EBS-DM at the genetic level. This mouse model differs from the human disease in that expression of the mutant K14 allele, which contains an Arg 131 Cys mutation equivalent to the Arg 125 Cys mutation found in the majority of EBS-DM patients, can be restricted to a small area of the skin. This mouse model has provided an explanation for the lack of mosaic forms of EBS. Patients with mostly normal skin that have patches of diseased skin are referred to as mosaics. Mosaic patients have been described for several skin diseases, but not for EBS. Focal activation of the mutant K14 gene by topical application of an inducer results in blister formation. However, after a few weeks, the blister heals and never reappears. We have demonstrated that the mutant K14 gene was activated in epidermal stern cells. However, the defective EBS stem cells were replaced by normal epidermal stem cells that migrate in from the untreated area surrounding the blister. This mouse model predicts that if a mosaic patch of EBS skin formed during development of an embryo, these defective EBS epidermal stem cells would not survive, but be replaced by normal stem cells. This explains the absence of mosaic forms of EBS. This observation also has important implications for gene therapy approaches for EBS, since it suggests that if EBS stem cells were removed from a patient, genetically corrected and then returned to a blistered area, they would have a selective growth advantage over defective EBS stem cells. Of further interest was the observation that mice which express the mutant K14 allele at levels approximately 50% of wild type K14 fail to exhibit a skin phenotype. This suggests that as long as the ratio of wild type to mutant K14 is above a threshold, possibly as low as 2:1, the skin will have a normal appearance and be fully functional. Thus, successful gene therapy approaches may not require correction or complete suppression of the mutant allele. This proposal will use epidermal stem cells isolated from the EBS-DM mouse model to test new gene therapy strategies that are based on these novel findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TYPE II KERATIN GENES /PROTEINS IN COMPLEX EPITHELIA Principal Investigator & Institution: Coulombe, Pierre A.; Professor; Biological Chemistry; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 15-JUN-1995; Project End 30-JUN-2008 Summary: (provided by applicant): Keratins are the most abundant proteins in epithelial cells, in which they occur as a cytoplasmic network of 10-12 nm wide intermediate filaments (IFs). They are encoded by an evolutionarily conserved multigene family, with > 49 individual members subdivided into two major types. The pairwise regulation of type I and type II keratin genes reflects a heteropolymerization requirement shared by all keratin IFs. Most keratin genes are regulated in pairwise, epithelial tissue-type and

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differentiation-specific fashion, the functional basis of which remains ill understood. A major role fulfilled by keratin IFs is to act as a resilient yet pliable scaffold that endows epithelial cells with the ability to sustain mechanical and non-mechanical stresses. Inherited mutations affecting the coding sequence of keratins are responsible for a large number of epithelial fragility disorders. Additional functions, manifested in a sequenceand context-dependent fashion, have been identified in recent years. Here we seek to further our understanding of the properties and functions of type II keratins expressed in complex epithelial tissues, including K1, K5 and K6 isoforms, and test our model that differential keratin expression leads to distinct mechanical attributes for keratinocytes. First, we will test the ability of K1 to rescue the striking epithelial defects that occur in K6 isoform null mice. We will concentrate on the epithelial fragility in the oral mucosa and the altered wound epithelialization phenotype seen in these mice. Second, we will investigate the biochemical and genetic bases for the strain-dependency of the enhanced migration exhibited by K6 isoform null keratinocytes in an ex vivo model of wound epithelialization. Third, we will assess the specific contribution of keratin IFs to the viscoelastic properties of live epithelial cells. Fourth, we will test the notion that the selfinduced ability of keratin IFs to undergo bundle formation is required for their scaffolding function in vivo. In particular, we will focus on the contribution of nonhelical C-terminal tail domains to filament bundling and function. The proposed research will provide insight into keratin filament organization and function, the significance of differential keratin expression, and the mechanisms underlying blister formation in keratin-based blistering diseases. 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 “epidermolysis bullosa” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for epidermolysis bullosa in the PubMed Central database: •

Complete Cytolysis and Neonatal Lethality in Keratin 5 Knockout Mice Reveal Its Fundamental Role in Skin Integrity and in Epidermolysis Bullosa Simplex. by Peters B, Kirfel J, Bussow H, Vidal M, Magin TM.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37340

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Disease Severity Correlates with Position of Keratin Point Mutations in Patients with Epidermolysis Bullosa Simplex. by Letai A, Coulombe PA, McCormick MB, Yu Q, Hutton E, Fuchs E.; 1993 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46266

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

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

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Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype. by Hovnanian A, Duquesnoy P, Amselem S, Blanchet-Bardon C, Lathrop M, Dubertret L, Goossens M.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295711

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Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene. by Hovnanian A, Duquesnoy P, Blanchet-Bardon C, Knowlton RG, Amselem S, Lathrop M, Dubertret L, Uitto J, Goossens M.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329960

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Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic epidermolysis bullosa in families with abnormal anchoring fibrils. by Ryynanen M, Ryynanen J, Sollberg S, Iozzo RV, Knowlton RG, Uitto J.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442946

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Herlitz junctional epidermolysis bullosa keratinocytes display heterogeneous defects of nicein/kalinin gene expression. by Baudoin C, Miquel C, Blanchet-Bardon C, Gambini C, Meneguzzi G, Ortonne JP.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293950

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Human Skin Collagenase in Recessive Dystrophic Epidermolysis Bullosa PURIFICATION OF A MUTANT ENZYME FROM FIBROBLAST CULTURES. by Stricklin GP, Welgus HG, Bauer EA.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370210

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Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. by Ortiz-Urda S, Lin Q, Green CL, Keene DR, Marinkovich MP, Khavari PA.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151880

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Molecular genetics of the cutaneous basement membrane zone. Perspectives on epidermolysis bullosa and other blistering skin diseases. by Uitto J, Christiano AM.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329917

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Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen. by Woodley DT, O'Keefe EJ, McDonald JA, Reese MJ, Briggaman RA, Gammon WR.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=424526

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The Genetic Basis of Epidermolysis Bullosa Simplex with Mottled Pigmentation. by Uttam J, Hutton E, Coulombe PA, Anton-Lamprecht I, Yu Q, Gedde-Dahl T, Fine J, Fuchs E.; 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38598

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The Genetic Basis of Weber-Cockayne Epidermolysis Bullosa Simplex. by Chan Y, Yu Q, Fine J, Fuchs E.; 1993 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47148

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with epidermolysis bullosa, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “epidermolysis bullosa” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for epidermolysis bullosa (hyperlinks lead to article summaries): •

A case of anti-p200 pemphigoid clinically mimicking inflammatory epidermolysis bullosa acquisita. Author(s): Umemoto N, Demitsu T, Toda S, Noguchi T, Suzuki SI, Kakurai M, Yamada T, Suzuki M, Nakagawa H, Komai A, Hashimoto T. Source: The British Journal of Dermatology. 2003 May; 148(5): 1058-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786845

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A comparative study of immunohistochemistry and electron microscopy used in the diagnosis of epidermolysis bullosa. Author(s): Petronius D, Bergman R, Ben Izhak O, Leiba R, Sprecher E. Source: The American Journal of Dermatopathology. 2003 June; 25(3): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775981

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A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency. Author(s): Bauer JW, Rouan F, Kofler B, Rezniczek GA, Kornacker I, Muss W, Hametner R, Klausegger A, Huber A, Pohla-Gubo G, Wiche G, Uitto J, Hintner H. Source: American Journal of Pathology. 2001 February; 158(2): 617-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11159198

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

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A founder COL17A1 splice site mutation leading to generalized atrophic benign epidermolysis bullosa in an extended inbred Palestinian family from Israel. Author(s): Whittock NV, Sher C, Gold I, Libman V, Reish O. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2003 November-December; 5(6): 435-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614394

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A homozygous nonsense mutation in type XVII collagen gene (COL17A1) uncovers an alternatively spliced mRNA accounting for an unusually mild form of non-Herlitz junctional epidermolysis bullosa. Author(s): Ruzzi L, Pas H, Posteraro P, Mazzanti C, Didona B, Owaribe K, Meneguzzi G, Zambruno G, Castiglia D, D'Alessio M. Source: The Journal of Investigative Dermatology. 2001 January; 116(1): 182-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168815

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A missense mutation (G1506E) in the adhesion G domain of laminin-5 causes mild junctional epidermolysis bullosa. Author(s): Scaturro M, Posteraro P, Mastrogiacomo A, Zaccaria ML, De Luca N, Mazzanti C, Zambruno G, Castiglia D. Source: Biochemical and Biophysical Research Communications. 2003 September 12; 309(1): 96-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943669

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A new glycine substitution mutation in the COL7A1 gene in a Chinese family with dominant dystrophic epidermolysis bullosa. Author(s): Zhang XJ, Song YX, Zhang XQ, Yang S, Li M, Li CR, Yang CJ, Yang J. Source: Clinical and Experimental Dermatology. 2003 July; 28(4): 437-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823310

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A new keratin 5 mutation (K199T) in a family with Weber-Cockayne epidermolysis bullosa simplex. Author(s): Xu Z, Dong H, Sun X, Zhu X, Yang Y. Source: Clinical and Experimental Dermatology. 2004 January; 29(1): 74-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723728

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A novel insertion mutation in COL7A1 identified in Hallopeau-Siemens recessive dystrophic epidermolysis bullosa. Author(s): Sato-Matsumura KC, Sawamura D, Goto M, Goto M, Nakamura H, Shimizu H. Source: Acta Dermato-Venereologica. 2003; 83(2): 137-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12735646

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A novel missense mutation in the COL7A1 gene underlies epidermolysis bullosa pruriginosa. Author(s): Chuang GS, Martinez-Mir A, Yu HS, Sung FY, Chuang RY, CserhalmiFriedman PB, Christiano AM. Source: Clinical and Experimental Dermatology. 2004 May; 29(3): 304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15115517

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A usual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema. Author(s): Gu LH, Kim SC, Ichiki Y, Park J, Nagai M, Kitajima Y. Source: The Journal of Investigative Dermatology. 2003 September; 121(3): 482-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925204

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A very mild form of non-Herlitz junctional epidermolysis bullosa: BP180 rescue by outsplicing of mutated exon 30 coding for the COL15 domain. Author(s): Pasmooij AM, van Zalen S, Nijenhuis AM, Kloosterhuis AJ, Zuiderveen J, Jonkman MF, Pas HH. Source: Experimental Dermatology. 2004 February; 13(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15009107

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Acellular dermal matrix allograft used to gain attached gingiva in a case of epidermolysis bullosa. Author(s): Buduneli E, Ilgenli T, Buduneli N, Ozdemir F. Source: Journal of Clinical Periodontology. 2003 November; 30(11): 1011-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14761125

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Acquired epidermolysis bullosa and Crohn's disease. Author(s): Gluck M, Kayne A. Source: Gastrointestinal Endoscopy. 2003 April; 57(4): 563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665771

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Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia. Author(s): Ashton GH, Sorelli P, Mellerio JE, Keane FM, Eady RA, McGrath JA. Source: The British Journal of Dermatology. 2001 February; 144(2): 408-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251584

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An autocrine/paracrine loop linking keratin 14 aggregates to tumor necrosis factor alpha-mediated cytotoxicity in a keratinocyte model of epidermolysis bullosa simplex. Author(s): Yoneda K, Furukawa T, Zheng YJ, Momoi T, Izawa I, Inagaki M, Manabe M, Inagaki N. Source: The Journal of Biological Chemistry. 2004 February 20; 279(8): 7296-303. Epub 2003 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660619

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An inducible mouse model for epidermolysis bullosa simplex: implications for gene therapy. Author(s): Cao T, Longley MA, Wang XJ, Roop DR. Source: The Journal of Cell Biology. 2001 February 5; 152(3): 651-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157990

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Apligraf in the treatment of severe mitten deformity associated with recessive dystrophic epidermolysis bullosa. Author(s): Fivenson DP, Scherschun L, Cohen LV. Source: Plastic and Reconstructive Surgery. 2003 August; 112(2): 584-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900618

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Are children with recessive dystrophic epidermolysis bullosa of low birthweight? Author(s): Fox AT, Alderdice F, Atherton DJ. Source: Pediatric Dermatology. 2003 July-August; 20(4): 303-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869148

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Assessment of mobility, activities and pain in different subtypes of epidermolysis bullosa. Author(s): Fine JD, Johnson LB, Weiner M, Suchindran C. Source: Clinical and Experimental Dermatology. 2004 March; 29(2): 122-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987264

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Babes, blisters and basement membranes: from sticky molecules to epidermolysis bullosa. Author(s): Eady RA. Source: Clinical and Experimental Dermatology. 1987 May; 12(3): 161-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3319296

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Balloon dilation of an esophageal stenosis in a patient with recessive dystrophic epidermolysis bullosa. Author(s): Naehrlich L, Lang T, Schamberger U, Behrens R. Source: Pediatric Dermatology. 2000 November-December; 17(6): 477-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123785

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Basic fibroblast growth factor: a missing link between collagen VII, increased collagenase, and squamous cell carcinoma in recessive dystrophic epidermolysis bullosa. Author(s): Arbiser JL, Fine JD, Murrell D, Paller A, Connors S, Keough K, Marsh E, Folkman J. Source: Molecular Medicine (Cambridge, Mass.). 1998 March; 4(3): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9562977

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Behavior of epidermolysis bullosa fibroblasts in a hydrated collagen lattice. Author(s): Eisen AZ, Pentland AP, Bauer EA, Goldberg GI. Source: The Journal of Investigative Dermatology. 1987 June; 88(6): 741-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3035032

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Benign junctional epidermolysis bullosa in three related Moroccan families. Author(s): Hacham-Zadeh S. Source: Journal of the American Academy of Dermatology. 1986 March; 14(3): 508-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3958264

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Bilateral corneal involvement in epidermolysis bullosa acquisita. Author(s): Dantas PE, Nishiwaki-Dantas MC, Seguim MH, Cursino JW. Source: Cornea. 2001 August; 20(6): 664-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11473173

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Biochemical defects in epidermolysis bullosa--a review. Author(s): Johnson L, Eisenberg M. Source: The Australasian Journal of Dermatology. 1986 April; 27(1): 11-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3530233

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Biology of anchoring fibrils: lessons from dystrophic epidermolysis bullosa. Author(s): Bruckner-Tuderman L, Hopfner B, Hammami-Hauasli N. Source: Matrix Biology : Journal of the International Society for Matrix Biology. 1999 February; 18(1): 43-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367730

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Blistering eruption in healthy newborns. Case 1. Epidermolysis bullosa simplex. Author(s): Pfau RG, Patel HP. Source: Archives of Dermatology. 1986 February; 122(2): 211, 214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3947129

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Blistering eruption in healthy newborns. Case 2. Junctional epidermolysis bullosa. Author(s): Cohen BA, Patel HP. Source: Archives of Dermatology. 1986 February; 122(2): 212, 214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3947130

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Blistering eruption in healthy newborns. Case 3. Epidermolysis bullosa dystrophica. Author(s): Pfau RG, Watson R, Patel HP. Source: Archives of Dermatology. 1986 February; 122(2): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3947131

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Blood vitamin and trace metal levels in epidermolysis bullosa. Author(s): Fine JD, Tamura T, Johnson L. Source: Archives of Dermatology. 1989 March; 125(3): 374-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2923444

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Bone metabolism in children with epidermolysis bullosa. Author(s): Reyes ML, Cattani A, Gajardo H, Garcia C, McGrath JA, Palisson F. Source: The Journal of Pediatrics. 2002 April; 140(4): 467-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006964

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Brachial plexus anesthesia in eight patients with recessive dystrophic epidermolysis bullosa. Author(s): Kelly RE, Koff HD, Rothaus KO, Carter DM, Artusio JF Jr. Source: Anesthesia and Analgesia. 1987 December; 66(12): 1318-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3688505

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Brunsting-Perry cicatricial bullous pemphigoid: a clinical variant of localized acquired epidermolysis bullosa? Author(s): Joly P, Ruto F, Thomine E, Delpech A, Balguerie X, Tron F, Lauret P. Source: Journal of the American Academy of Dermatology. 1993 January; 28(1): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8425977

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Bullous pemphigoid and epidermolysis bullosa acquisita. Differentiation by fluorescence overlay antigen mapping. Author(s): De Jong MC, Bruins S, Heeres K, Jonkman MF, Nieboer C, Boorsma DM, Pas HH, van der Meer JB. Source: Archives of Dermatology. 1996 February; 132(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8629822

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Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis, and immunopathology in 11 children. Author(s): Edwards S, Wakelin SH, Wojnarowska F, Marsden RA, Kirtschig G, Bhogal B, Black MM. Source: Pediatric Dermatology. 1998 May-June; 15(3): 184-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9655312

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Bullous pemphigoid antigens (BPAGs): identification of RFLPs in human BPAG1 and BPAG2, and exclusion as candidate genes in a large kindred with dominant epidermolysis bullosa simplex. Author(s): Ryynanen M, Knowlton RG, Kero M, Sawamura D, Li KH, Giudice GJ, Diaz LA, Uitto J. Source: Genomics. 1991 December; 11(4): 1025-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1686013

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Bullous systemic lupus erythematosus: an unusual clinical course and detectable circulating autoantibodies to the epidermolysis bullosa acquisita antigen. Author(s): Barton DD, Fine JD, Gammon WR, Sams WM Jr. Source: Journal of the American Academy of Dermatology. 1986 August; 15(2 Pt 2): 36973. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3525621

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Case report: cleft palate closure in 18-month-old female with epidermolysis bullosa. Author(s): Cooper J, O SJ, Thaller SR. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2003 January; 40(1): 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498611

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Characterization of mutations leading to recessive dystrophic epidermolysis bullosa and Marfan syndrome in a single patient. Author(s): Gardella R, Nuytinck L, Barlati S, Van Acker P, Tadini G, De Paepe A, Colombi M. Source: Clinical and Experimental Dermatology. 2001 November; 26(8): 710-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11722462

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Characterization of mutations of the type VII collagen gene (COL7A1) in recessive dystrophic epidermolysis bullosa mitis (M-RDEB) from three Korean patients. Author(s): Ryoo YW, Kim BC, Lee KS. Source: Journal of Dermatological Science. 2001 June; 26(2): 125-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378329

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Chemoprevention of squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: results of a phase 1 trial of systemic isotretinoin. Author(s): Fine JD, Johnson LB, Weiner M, Stein A, Suchindran C. Source: Journal of the American Academy of Dermatology. 2004 April; 50(4): 563-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15034505

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Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all three structural domains of type VII collagen. Author(s): Schmidt E, Hopfner B, Chen M, Kuhn C, Weber L, Brocker EB, BrucknerTuderman L, Zillikens D. Source: The British Journal of Dermatology. 2002 September; 147(3): 592-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207608

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Clinical application of amniotic membranes on a patient with epidermolysis bullosa. Author(s): Martinez Pardo ME, Reyes Frias ML, Ramos Duron LE, Gutierrez Salgado E, Gomez JC, Marin MA, Luna Zaragoza D. Source: Ann Transplant. 1999; 4(3-4): 68-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10853786

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Clinical evaluation of patients with epidermolysis bullosa: review of the literature and case reports. Author(s): Silva LC, Cruz RA, Abou-Id LR, Brini LN, Moreira LS. Source: Spec Care Dentist. 2004 January-February; 24(1): 22-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15157056

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Clinical trial of allogeneic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa. Author(s): Hasegawa T, Suga Y, Mizoguchi M, Ikeda S, Ogawa H, Kubo K, Matsui H, Kagawa S, Kuroyanagi Y. Source: Journal of the American Academy of Dermatology. 2004 May; 50(5): 803-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15097978

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Clinicopathological case 1: mucous membrane pemphigoid, epidermolysis bullosa acquisita and linear immunoglobulin A disease. Author(s): Harman KE, Setterfield JF, Shirlaw PJ, Black MM, Challacombe SJ. Source: Clinical and Experimental Dermatology. 2003 July; 28(4): 461-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823323

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Colchicine therapy in amyloid nephropathy due to recessive dystrophic epidermolysis bullosa. Author(s): Kaneko K, Someya T, Ohtaki R, Shimojima T, Yamashiro Y, Ohtomo Y. Source: Pediatric Nephrology (Berlin, Germany). 2003 December; 18(12): 1311-2. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586686

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Colon interposition for esophageal stenosis in a patient with epidermolysis bullosa. Author(s): Demirogullari B, Sonmez K, Turkyilmaz Z, Altuntas B, Karabulut R, Basaklar AC, Kale N. Source: Journal of Pediatric Surgery. 2001 December; 36(12): 1861-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733926

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Combined anaesthesia in a young patient with dystrophic epidermolysis bullosa. Author(s): Benavente MA, Sanchez-Guijo JJ. Source: Paediatric Anaesthesia. 2003 March; 13(3): 274. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641694

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Complete cytolysis and neonatal lethality in keratin 5 knockout mice reveal its fundamental role in skin integrity and in epidermolysis bullosa simplex. Author(s): Peters B, Kirfel J, Bussow H, Vidal M, Magin TM. Source: Molecular Biology of the Cell. 2001 June; 12(6): 1775-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408584

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Compound heterozygosity for a point mutation and a deletion located at splice acceptor sites in the LAMB3 gene leads to generalized atrophic benign epidermolysis bullosa. Author(s): Takizawa Y, Hiraoka Y, Takahashi H, Ishiko A, Yasuraoka I, Hashimoto I, Aiso S, Nishikawa T, Shimizu H. Source: The Journal of Investigative Dermatology. 2000 August; 115(2): 312-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10951252

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Comprehensive analysis of gene expression profiles in keratinocytes from patients with generalized atrophic benign epidermolysis bullosa. Author(s): Huber A, Yee C, Darling TN, Yancey KB. Source: Experimental Dermatology. 2002 February; 11(1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952829

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Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa. Author(s): Kambham N, Tanji N, Seigle RL, Markowitz GS, Pulkkinen L, Uitto J, D'Agati VD. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 July; 36(1): 190-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10873890

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Congenital pyloric atresia in a newborn with extensive aplasia cutis congenita and epidermolysis bullosa simplex. Author(s): Morrell DS, Rubenstein DS, Briggaman RA, Fine JD, Pulkkinen L, Uitto J. Source: The British Journal of Dermatology. 2000 December; 143(6): 1342-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122061

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Continuous axillary block for upper limb surgery in a patient with epidermolysis bullosa simplex. Author(s): Diwan R, Vas L, Shah T, Raghavendran S, Ponde V. Source: Paediatric Anaesthesia. 2001; 11(5): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11696126

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Crusted scabies in a girl with epidermolysis bullosa simplex. Author(s): Torrelo A, Zambrano A. Source: The British Journal of Dermatology. 2000 January; 142(1): 197-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819560

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Cultured keratinocytes from plectin/HD1-deficient epidermolysis bullosa simplex showed altered ability of adhesion to the matrix. Author(s): Kurose K, Mori O, Hachisuka H, Shimizu H, Owaribe K, Hashimoto T. Source: Journal of Dermatological Science. 2000 December; 24(3): 184-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084300

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Deletion of a cytoplasmic domain of integrin beta4 causes epidermolysis bullosa simplex. Author(s): Jonkman MF, Pas HH, Nijenhuis M, Kloosterhuis G, Steege G. Source: The Journal of Investigative Dermatology. 2002 December; 119(6): 1275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485428

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Deletion of the cytoplasmatic domain of BP180/collagen XVII causes a phenotype with predominant features of epidermolysis bullosa simplex. Author(s): Huber M, Floeth M, Borradori L, Schacke H, Rugg EL, Lane EB, Frenk E, Hohl D, Bruckner-Tuderman L. Source: The Journal of Investigative Dermatology. 2002 January; 118(1): 185-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11851893

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Dental disease and caries related microflora in children with dystrophic epidermolysis bullosa. Author(s): Harris JC, Bryan RA, Lucas VS, Roberts GJ. Source: Pediatr Dent. 2001 September-October; 23(5): 438-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11699172

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Dental maturity in children with dystrophic epidermolysis bullosa. Author(s): Kostara A, Roberts GJ, Gelbier M. Source: Pediatr Dent. 2000 September-October; 22(5): 385-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11048306

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Diagnosis and prenatal diagnosis of epidermolysis bullosa herpetiformis (DowlingMeara) in a mother, two affected children, and an affected fetus. Author(s): Holbrook KA, Wapner R, Jackson L, Zaeri N. Source: Prenatal Diagnosis. 1992 September; 12(9): 725-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1438067

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Differences in direct immunofluorescence staining patterns in epidermolysis bullosa acquisita and bullous pemphigoid. Author(s): Smoller BR, Woodley DT. Source: Journal of the American Academy of Dermatology. 1992 November; 27(5 Pt 1): 674-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1430385

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Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene. Author(s): Gardella R, Zoppi N, Zambruno G, Barlati S, Colombi M. Source: The British Journal of Dermatology. 2002 September; 147(3): 450-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207583

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Dilated cardiomyopathy in dystrophic epidermolysis bullosa: a lethal complication of epidermolysis bullosa. Author(s): Cunnington PM, Addison R. Source: European Journal of Anaesthesiology. 2002 September; 19(9): 689-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243296

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Dilation of an esophageal stricture caused by epidermolysis bullosa. Author(s): Postma GN, Belafsky PC, Koufman JA. Source: Ear, Nose, & Throat Journal. 2002 February; 81(2): 86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11868478

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Dilemmas in distinguishing between dominant and recessive forms of dystrophic epidermolysis bullosa. Author(s): Mallipeddi R, Bleck O, Mellerio JE, Ashton GH, Eady RA, McGrath JA. Source: The British Journal of Dermatology. 2003 October; 149(4): 810-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616374

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Disorganization of the desmin cytoskeleton and mitochondrial dysfunction in plectin-related epidermolysis bullosa simplex with muscular dystrophy. Author(s): Schroder R, Kunz WS, Rouan F, Pfendner E, Tolksdorf K, Kappes-Horn K, Altenschmidt-Mehring M, Knoblich R, van der Ven PF, Reimann J, Furst DO, Blumcke I, Vielhaber S, Zillikens D, Eming S, Klockgether T, Uitto J, Wiche G, Rolfs A. Source: Journal of Neuropathology and Experimental Neurology. 2002 June; 61(6): 52030. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12071635

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DNA based molecular analysis in the rapid diagnosis of Herlitz junctional epidermolysis bullosa. Author(s): Cserhalmi-Friedman PB, Yeboa KA, Christiano AM. Source: Clinical and Experimental Dermatology. 2001 March; 26(2): 205-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298117

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Dominant and recessive compound heterozygous mutations in epidermolysis bullosa simplex demonstrate the role of the stutter region in keratin intermediate filament assembly. Author(s): Yasukawa K, Sawamura D, McMillan JR, Nakamura H, Shimizu H. Source: The Journal of Biological Chemistry. 2002 June 28; 277(26): 23670-4. Epub 2002 April 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973334

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Dominant dystrophic epidermolysis bullosa associated with pyloric stenosis and congenital absence of skin. Author(s): Dereure O, Vailly J, Lagrange B, Meneguzzi G, Ortonne JP, Guillot B. Source: Archives of Dermatology. 2001 May; 137(5): 665-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346353

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Dominant dystrophic epidermolysis bullosa presenting as familial nail dystrophy. Author(s): Dharma B, Moss C, McGrath JA, Mellerio JE, Ilchyshyn A. Source: Clinical and Experimental Dermatology. 2001 January; 26(1): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260188

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Drug-induced epidermolysis bullosa acquisita with antibodies to type VII collagen. Author(s): Delbaldo C, Chen M, Friedli A, Prins C, Desmeules J, Saurat JH, Woodley DT, Borradori L. Source: Journal of the American Academy of Dermatology. 2002 May; 46(5 Suppl): S1614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004302

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Dystrophic epidermolysis bullosa complicated by cutaneous squamous cell carcinoma and pulmonary and renal amyloidosis. Author(s): Csikos M, Orosz Z, Bottlik G, Szocs H, Szalai Z, Rozgonyi Z, Harsing J, Torok E, Bruckner-Tuderman L, Horvath A, Karpati S. Source: Clinical and Experimental Dermatology. 2003 March; 28(2): 163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653705

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Dystrophic epidermolysis bullosa inversa with COL7A1 mutations and absence of GDA-J/F3 protein. Author(s): Kahofer P, Bruckner-Tuderman L, Metze D, Lemmink H, Scheffer H, Smolle J. Source: Pediatric Dermatology. 2003 May-June; 20(3): 243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787275

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Dystrophic epidermolysis bullosa with epidermal neoplasms with emphasis on a dermal collagen defect. Author(s): Reed WB, Torres-Rodriguez V, Francis MJ, Ryan T, Torres C. Source: Birth Defects Orig Artic Ser. 1975; 11(6): 153-66. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1103992

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Dystrophic epidermolysis bullosa. Author(s): Das BB, Sahoo S. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2004 January; 24(1): 41-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726937

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Efficacy and safety of endoscopic dilation of esophageal strictures in epidermolysis bullosa. Author(s): Anderson SH, Meenan J, Williams KN, Eady RA, Prinja H, Chappiti U, Doig L, Thompson RP. Source: Gastrointestinal Endoscopy. 2004 January; 59(1): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722543

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Emerging treatment for epidermolysis bullosa acquisita. Author(s): Engineer L, Ahmed AR. Source: Journal of the American Academy of Dermatology. 2001 May; 44(5): 818-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11312431

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Epidermolysis bullosa acquisita and multiple myeloma. Author(s): Engineer L, Dow EC, Braverman IM, Ahmed AR. Source: Journal of the American Academy of Dermatology. 2002 December; 47(6): 943-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451384

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Epidermolysis bullosa acquisita in an 8-year-old girl. Author(s): Wu JJ, Wagner AM. Source: Pediatric Dermatology. 2002 July-August; 19(4): 368-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220292

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Epidermolysis bullosa acquisita in childhood. Author(s): Trigo-Guzman FX, Conti A, Aoki V, Maruta CW, Santi CG, Resende Silva CM, Gontijo B, Woodley DT, Rivitti EA. Source: The Journal of Dermatology. 2003 March; 30(3): 226-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692360

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Epidermolysis bullosa acquisita sera react with distinct epitopes on the NC1 and NC2 domains of type VII collagen: study using immunoblotting of domain-specific recombinant proteins and postembedding immunoelectron microscopy. Author(s): Ishii N, Yoshida M, Hisamatsu Y, Ishida-Yamamoto A, Nakane H, Iizuka H, Tanaka T, Hashimoto T. Source: The British Journal of Dermatology. 2004 May; 150(5): 843-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15149495

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Epidermolysis bullosa acquisita: clinical manifestations, microscopic findings, and surgical periodontal therapy. A case report. Author(s): Hakki SS, Celenligil-Nazliel H, Karaduman A, Usubutun A, Ertoy D, Ayhan A, Ruacan S. Source: J Periodontol. 2001 April; 72(4): 550-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11338310

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Epidermolysis bullosa acquisita-like reaction associated with penicillamine therapy for sclerodermatous graft-versus-host disease. Author(s): Cetkovska P, Pizinger K, Skalova A. Source: Journal of the American Academy of Dermatology. 2003 December; 49(6): 11579. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639407

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Epidermolysis bullosa and cancer. Author(s): Mallipeddi R. Source: Clinical and Experimental Dermatology. 2002 November; 27(8): 616-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472531

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Epidermolysis bullosa carrier frequencies in the US population. Author(s): Pfendner E, Uitto J, Fine JD. Source: The Journal of Investigative Dermatology. 2001 March; 116(3): 483-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231335

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Epidermolysis bullosa simplex in Israel: clinical and genetic features. Author(s): Ciubotaru D, Bergman R, Baty D, Indelman M, Pfendner E, Petronius D, Moualem H, Kanaan M, Ben Amitai D, McLean WH, Uitto J, Sprecher E. Source: Archives of Dermatology. 2003 April; 139(4): 498-505. Erratum In: Arch Dermatol. 2003 August; 139(8): 1084. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707098

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Epidermolysis bullosa simplex keratinocytes with extended lifespan established by ectopic expression of telomerase. Author(s): Jensen TG, Sorensen CB, Jensen UB, Bolund L. Source: Experimental Dermatology. 2003 February; 12(1): 71-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631249

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Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations. Author(s): Nakano A, Pulkkinen L, Murrell D, Rico J, Lucky AW, Garzon M, Stevens CA, Robertson S, Pfendner E, Uitto J. Source: Pediatric Research. 2001 May; 49(5): 618-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11328943

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Epidermolysis bullosa. Author(s): Pillay E. Source: British Journal of Nursing (Mark Allen Publishing). 2003 October; 12(19 Suppl): S43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619258

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Epidermolysis bullosa: directions for future research and new challenges for treatment. Author(s): Sawamura D, McMillan JR, Akiyama M, Shimizu H. Source: Archives of Dermatological Research. 2003 April; 295 Suppl 1: S34-42. Epub 2003 March 05. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677431

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Epidermolysis bullosa: identification and treatment. Author(s): Trent JT, Kirsner RS. Source: Advances in Skin & Wound Care. 2003 November; 16(6): 284-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652513

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Epidermolysis bullosa: the challenges of wound care. Author(s): Schober-Flores C. Source: Dermatology Nursing / Dermatology Nurses' Association. 2003 April; 15(2): 135-8, 141-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751349

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Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the v2 tail domains of keratin 1 and keratin 5. Author(s): Sprecher E, Yosipovitch G, Bergman R, Ciubutaro D, Indelman M, Pfendner E, Goh LC, Miller CJ, Uitto J, Richard G. Source: The Journal of Investigative Dermatology. 2003 April; 120(4): 623-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648226

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Eruptive large melanocytic nevus in a patient with hereditary epidermolysis bullosa simplex. Author(s): Stavrianeas NG, Katoulis AC, Moussatou V, Bozi E, Petropoulou H, Limas C, Georgala S. Source: Dermatology (Basel, Switzerland). 2003; 207(4): 402-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657636

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Expression profiles of collagens, HSP47, TGF-beta1, MMPs and TIMPs in epidermolysis bullosa acquisita. Author(s): Razzaque MS, Kumari S, Foster CS, Ahmed AR. Source: Cytokine. 2003 March 7; 21(5): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824005

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Failure of human growth hormone to benefit dystrophic epidermolysis bullosa. Author(s): Zackheim HS. Source: Archives of Dermatology. 1983 July; 119(7): 537. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6859895

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Familial epidermolysis bullosa with aplasia cutis congenita: Bart's syndrome? Author(s): Benvenuto C, Kraemer CK, Kruse RL, Cestari TF. Source: Skinmed. 2003 September-October; 2(5): 319-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673268

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Familial pyloric atresia associated with epidermolysis bullosa. Author(s): Swinburne LM, Kohler HG. Source: The Journal of Pediatrics. 1979 January; 94(1): 162. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=758404

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Familial pyloric atresia associated with epidermolysis bullosa. Author(s): De Groot WG, Postuma R, Hunter AG. Source: The Journal of Pediatrics. 1978 March; 92(3): 429-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=632984

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Fatal cardiomyopathy in dystrophic epidermolysis bullosa. Author(s): Melville C, Atherton D, Burch M, Cohn A, Sullivan I. Source: The British Journal of Dermatology. 1996 October; 135(4): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915155

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Fatal systemic amyloidosis (AA type) in two sisters with dystrophic epidermolysis bullosa. Author(s): Bourke JF, Browne G, Gaffney EF, Young M. Source: Journal of the American Academy of Dermatology. 1995 August; 33(2 Pt 2): 3702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7615888

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Fatal vascular involvement in systemic lupus erythematosus following epidermolysis bullosa acquisita. Author(s): Yoon J, Moon TK, Lee KH, Kim SC. Source: Acta Dermato-Venereologica. 1995 March; 75(2): 143-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7604645

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Fibrillin immunoreactivity is associated with normal or fragmented elastic microfibrils at the dermal-epidermal junction in recessive dystrophic epidermolysis bullosa. Author(s): McGrath JA, Sakai LY, Eady RA. Source: The British Journal of Dermatology. 1994 October; 131(4): 465-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7947198

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First trimester DNA-based exclusion of recessive dystrophic epidermolysis bullosa from chorionic villus sampling. Author(s): McGrath JA, Dunnill MG, Christiano AM, Lake BD, Atherton DJ, Rodeck CH, Pope FM, Eady RA, Uitto J. Source: The British Journal of Dermatology. 1996 April; 134(4): 734-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8733382

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Five year followup of colonic transplants in patients with epidermolysis bullosa producing esophageal obstruction. Author(s): De Leon R, Mispireta LA, Absolon KB. Source: Med Ann Dist Columbia. 1974 May; 43(5): 241-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4526567

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Floor-pattern salt-split skin cannot distinguish bullous pemphigoid from epidermolysis bullosa acquisita. Use of toad skin. Author(s): Pang BK, Lee YS, Ratnam KV. Source: Archives of Dermatology. 1993 June; 129(6): 744-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8507077

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Fluoroscopically guided endoluminal balloon dilatation of esophageal stricture due to epidermolysis bullosa dystrophica. Author(s): Inal M, Soyupak S, Akgul E, Aksungur EH, Akinoglu A. Source: Dysphagia. 2002 Summer; 17(3): 242-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140654

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Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests. Author(s): Takizawa Y, Shimizu H, Rouan F, Kawai M, Udono M, Pulkkinen L, Nishikawa T, Uitto J. Source: The Journal of Investigative Dermatology. 1999 January; 112(1): 109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886273

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Frameshift mutations in the type VII collagen gene (COL7A1) in five Mexican cousins with recessive dystrophic epidermolysis bullosa. Author(s): Salas-Alanis JC, Mellerio JE, Amaya-Guerra M, Ashton GH, Eady RA, McGrath JA. Source: The British Journal of Dermatology. 1998 May; 138(5): 852-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9666834

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Free anterolateral thigh perforator flap for reconstruction of dystrophic epidermolysis bullosa-associated squamous cell carcinoma in the foot: case report. Author(s): Hsieh CH, Kuo YR, Huang PH, Jeng SF. Source: Annals of Plastic Surgery. 2003 February; 50(2): 201-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567061

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Functional heterogeneity of immune complexes in epidermolysis bullosa acquisita. Author(s): Gammon WR, Briggaman RA. Source: The Journal of Investigative Dermatology. 1987 November; 89(5): 478-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3668292

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Functional testing of keratin 14 mutant proteins associated with the three major subtypes of epidermolysis bullosa simplex. Author(s): Sorensen CB, Andresen BS, Jensen UB, Jensen TG, Jensen PK, Gregersen N, Bolund L. Source: Experimental Dermatology. 2003 August; 12(4): 472-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930305

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Gastric outlet obstruction and epidermolysis bullosa. Author(s): Shaw DW, Fine JD, Piacquadio DJ, Greenberg MJ, Wang-Rodriguez J, Eichenfield LF. Source: Journal of the American Academy of Dermatology. 1997 February; 36(2 Pt 2): 304-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039206

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Gastrostomy and growth in dystrophic epidermolysis bullosa. Author(s): Haynes L, Atherton DJ, Ade-Ajayi N, Wheeler R, Kiely EM. Source: The British Journal of Dermatology. 1996 May; 134(5): 872-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8736328

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Gene correction of integrin beta4-dependent pyloric atresia-junctional epidermolysis bullosa keratinocytes establishes a role for beta4 tyrosines 1422 and 1440 in hemidesmosome assembly. Author(s): Dellambra E, Prislei S, Salvati AL, Madeddu ML, Golisano O, Siviero E, Bondanza S, Cicuzza S, Orecchia A, Giancotti FG, Zambruno G, De Luca M. Source: The Journal of Biological Chemistry. 2001 November 2; 276(44): 41336-42. Epub 2001 August 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522777

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Generalized atrophic benign epidermolysis bullosa in 2 siblings complicated by multiple squamous cell carcinomas. Author(s): Swensson O, Christophers E. Source: Archives of Dermatology. 1998 February; 134(2): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9487212

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Generalized atrophic benign epidermolysis bullosa. Author(s): Darling TN, Bauer JW, Hintner H, Yancey KB. Source: Adv Dermatol. 1997; 13: 87-119; Discussion 120. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9551142

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Generalized atrophic benign epidermolysis bullosa: a case of severe hemidesmosomal deficiency. Author(s): Hashimoto K, Shwayder T. Source: The Journal of Dermatology. 1999 August; 26(8): 512-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487006

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Generalized atrophic benign epidermolysis bullosa--poor prognosis associated with chronic renal failure. Author(s): Woo HJ, Lee JH, Kim SC, Kim CW, Kim TY. Source: Clinical and Experimental Dermatology. 2000 May; 25(3): 212-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10844498

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Generalized dystrophic epidermolysis bullosa: identification of a novel, homozygous glycine substitution, G2031S, in exon 73 of COL7A1 in monozygous triplets. Author(s): Nordal EJ, Mecklenbeck S, Hausser I, Skranes J, Bruckner-Tuderman L, Gedde-Dahl T Jr. Source: The British Journal of Dermatology. 2001 January; 144(1): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167698

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Generalized gravis junctional epidermolysis bullosa: case report, laboratory evaluation, and review of recent advances. Author(s): Lim KK, Su WP, McEvoy MT, Pittelkow MR. Source: Mayo Clinic Proceedings. 1996 September; 71(9): 863-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8790263

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Generation and characterization of epidermolysis bullosa simplex cell lines: scratch assays show faster migration with disruptive keratin mutations. Author(s): Morley SM, D'Alessandro M, Sexton C, Rugg EL, Navsaria H, Shemanko CS, Huber M, Hohl D, Heagerty AI, Leigh IM, Lane EB. Source: The British Journal of Dermatology. 2003 July; 149(1): 46-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890194

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Genetic abnormalities and clinical classification of epidermolysis bullosa. Author(s): Mitsuhashi Y, Hashimoto I. Source: Archives of Dermatological Research. 2003 April; 295 Suppl 1: S29-33. Epub 2003 January 24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677430

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Genetic bases of severe junctional epidermolysis bullosa presenting spontaneous amelioration with aging. Author(s): Gache Y, Allegra M, Bodemer C, Pisani-Spadafora A, de Prost Y, Ortonne JP, Meneguzzi G. Source: Human Molecular Genetics. 2001 October 1; 10(21): 2453-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689492

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Genetic correction of canine dystrophic epidermolysis bullosa mediated by retroviral vectors. Author(s): Baldeschi C, Gache Y, Rattenholl A, Bouille P, Danos O, Ortonne JP, Bruckner-Tuderman L, Meneguzzi G. Source: Human Molecular Genetics. 2003 August 1; 12(15): 1897-905. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874109

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Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant form of dystrophic epidermolysis bullosa in two Dutch kindreds. Author(s): Gruis NA, Bavinck JN, Steijlen PM, van der Schroeff JG, van Haeringen A, Happle R, Mariman E, van Beersum SE, Uitto J, Vermeer BJ, et al. Source: The Journal of Investigative Dermatology. 1992 November; 99(5): 528-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1358979

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Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice-site mutation in a patient with junctional epidermolysis bullosa associated with pyloric atresia. Author(s): Pulkkinen L, Kurtz K, Xu Y, Bruckner-Tuderman L, Uitto J. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1997 June; 76(6): 823-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9194858

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Genotype-phenotype correlation in italian patients with dystrophic epidermolysis bullosa. Author(s): Gardella R, Castiglia D, Posteraro P, Bernardini S, Zoppi N, Paradisi M, Tadini G, Barlati S, McGrath JA, Zambruno G, Colombi M. Source: The Journal of Investigative Dermatology. 2002 December; 119(6): 1456-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485454

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Glycine substitution mutations by different amino acids in the same codon of COL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolysis bullosa. Author(s): Murata T, Masunaga T, Shimizu H, Takizawa Y, Ishiko A, Hatta N, Nishikawa T. Source: Archives of Dermatological Research. 2000 October; 292(10): 477-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142768

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Glycine substitution mutations in the type VII collagen gene (COL7A1) in dystrophic epidermolysis bullosa: implications for genetic counseling. Author(s): Kon A, McGrath JA, Pulkkinen L, Nomura K, Nakamura T, Maekawa Y, Christiano AM, Hashimoto I, Uitto J. Source: The Journal of Investigative Dermatology. 1997 February; 108(2): 224-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9008239

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Graftskin therapy in epidermolysis bullosa. Author(s): Fivenson DP, Scherschun L, Choucair M, Kukuruga D, Young J, Shwayder T. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 886-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789180

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Groin dissections in epidermolysis bullosa: a report of groin dissection for the control of metastatic squamous carcinoma in patients with epidermolysis bullosa. Author(s): Georgeu GA, Ramsey KW, El-Muttardi N, Mayou BJ. Source: British Journal of Plastic Surgery. 2002 December; 55(8): 678-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12550124

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Hand splintage following surgery for dystrophic epidermolysis bullosa. Author(s): Mullett FL, Smith PJ. Source: British Journal of Plastic Surgery. 1993 April; 46(3): 192-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8387856

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Hemidesmosomal variants of epidermolysis bullosa. Mutations in the alpha6beta4 integrin and the 180-kD bullous pemphigoid antigen/type XVII collagen genes. Author(s): Pulkkinen L, Uitto J. Source: Experimental Dermatology. 1998 April-June; 7(2-3): 46-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9583744

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Hemidesmosome assembly assessed by expression of a wild-type integrin beta 4 cDNA in junctional epidermolysis bullosa keratinocytes. Author(s): Gagnoux-Palacios L, Gache Y, Ortonne JP, Meneguzzi G. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1997 November; 77(5): 459-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9389789

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Hemidesmosomes show abnormal association with the keratin filament network in junctional forms of epidermolysis bullosa. Author(s): McMillan JR, McGrath JA, Tidman MJ, Eady RA. Source: The Journal of Investigative Dermatology. 1998 February; 110(2): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9457907

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Hereditary epidermolysis bullosa. Author(s): Wright JT, Fine JD. Source: Semin Dermatol. 1994 June; 13(2): 102-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8060821

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Hereditary epidermolysis bullosa. Dental management of three cases. Author(s): Serrano Martinez C, Silvestre Donat FJ, Bagan Sebastian JV, Penarrocha Diago M, Alio Sanz JJ. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2001 January-February; 6(1): 48-56. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488131

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Hereditary epidermolysis bullosa: oral manifestations and dental management. Author(s): Wright JT, Fine JD, Johnson L. Source: Pediatr Dent. 1993 July-August; 15(4): 242-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8247897

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Herlitz junctional epidermolysis bullosa keratinocytes display heterogeneous defects of nicein/kalinin gene expression. Author(s): Baudoin C, Miquel C, Blanchet-Bardon C, Gambini C, Meneguzzi G, Ortonne JP. Source: The Journal of Clinical Investigation. 1994 February; 93(2): 862-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8113417

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Herlitz junctional epidermolysis bullosa presenting at birth with anonychia: a case report and review of H-JEB. Author(s): Parsapour K, Reep MD, Mohammed L, Church A, Shwayder T. Source: Pediatric Dermatology. 2001 May-June; 18(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11438002

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Herlitz junctional epidermolysis bullosa: a case report and review of current diagnostic methods. Author(s): Basarab T, Dunnill MG, Eady RA, Russell-Jones R. Source: Pediatric Dermatology. 1997 July-August; 14(4): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263316

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Herlitz junctional epidermolysis bullosa: novel and recurrent mutations in the LAMB3 gene and the population carrier frequency. Author(s): Nakano A, Pfendner E, Hashimoto I, Uitto J. Source: The Journal of Investigative Dermatology. 2000 September; 115(3): 493-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11023379

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Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5). Author(s): Aberdam D, Galliano MF, Vailly J, Pulkkinen L, Bonifas J, Christiano AM, Tryggvason K, Uitto J, Epstein EH Jr, Ortonne JP, et al. Source: Nature Genetics. 1994 March; 6(3): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8012394

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Hermann Pinkus Memorial Lecture--1992. Autoimmunity to collagen VII: Autoantibody-mediated pathomechanisms regulate clinical-pathological phenotypes of acquired epidermolysis bullosa and bullous SLE. Author(s): Gammon WR. Source: Journal of Cutaneous Pathology. 1993 April; 20(2): 109-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8320353

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Heterogeneity of severe dystrophic epidermolysis bullosa: overexpression of collagen VII by cutaneous cells from a patient with mutilating disease. Author(s): Konig A, Winberg JO, Gedde-Dahl T Jr, Bruckner-Tuderman L. Source: The Journal of Investigative Dermatology. 1994 February; 102(2): 155-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8106746

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Heterogeneous reactivity with LH7.2 and the first prenatal diagnosis of generalized recessive dystrophic epidermolysis bullosa among Japanese patients. Author(s): Shimizu H, Suzumori K, Nishikawa T. Source: Dermatology (Basel, Switzerland). 1996; 192(3): 203-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8726631

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Heterozygosity for premature termination codon mutations in LAMB3 in siblings with non-lethal junctional epidermolysis bullosa. Author(s): Pulkkinen L, Uitto J. Source: The Journal of Investigative Dermatology. 1998 December; 111(6): 1244-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856855

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Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with congenital duodenal atresia. Author(s): Pulkkinen L, Kimonis VE, Xu Y, Spanou EN, McLean WH, Uitto J. Source: Human Molecular Genetics. 1997 May; 6(5): 669-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9158140

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Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Author(s): Pulkkinen L, Smith FJ, Shimizu H, Murata S, Yaoita H, Hachisuka H, Nishikawa T, McLean WH, Uitto J. Source: Human Molecular Genetics. 1996 October; 5(10): 1539-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8894687

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Homozygous nonsense mutation in helix 2 of K14 causes severe recessive epidermolysis bullosa simplex. Author(s): Corden LD, Mellerio JE, Gratian MJ, Eady RA, Harper JI, Lacour M, Magee G, Lane EB, McGrath JA, McLean WH. Source: Human Mutation. 1998; 11(4): 279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9554744

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Identification of a lethal form of epidermolysis bullosa simplex associated with a homozygous genetic mutation in plectin. Author(s): Charlesworth A, Gagnoux-Palacios L, Bonduelle M, Ortonne JP, De Raeve L, Meneguzzi G. Source: The Journal of Investigative Dermatology. 2003 December; 121(6): 1344-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675180

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Identification of a leucine-to-proline mutation in the keratin 5 gene in a family with the generalized Kobner type of epidermolysis bullosa simplex. Author(s): Dong W, Ryynanen M, Uitto J. Source: Human Mutation. 1993; 2(2): 94-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7686424

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Identification of mutations in the COL7A1 gene in a proband with mild recessive dystrophic epidermolysis bullosa and aortic insufficiency. Author(s): Horev L, Waran Lalin T, Martinez-Mir A, Bagheri BA, Tadin-Strapps M, Schneiderman PI, Grossman ME, Bickers DR, Christiano AM. Source: Clinical and Experimental Dermatology. 2003 January; 28(1): 80-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558638

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Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa. Author(s): Gardella R, Belletti L, Zoppi N, Marini D, Barlati S, Colombi M. Source: American Journal of Human Genetics. 1996 August; 59(2): 292-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8755915

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IgA-mediated epidermolysis bullosa acquisita: two cases and review of the literature. Author(s): Vodegel RM, de Jong MC, Pas HH, Jonkman MF. Source: Journal of the American Academy of Dermatology. 2002 December; 47(6): 91925. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451379

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IgM-mediated epidermolysis bullosa acquisita. Author(s): Suchniak JM, Diaz LA, Lin MS, Fairley JA. Source: Archives of Dermatology. 2002 October; 138(10): 1385-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12374560

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Immunofluorescence studies using skin sections of recessive dystrophic epidermolysis bullosa patients indicated that the antigen of anti-p200 pemphigoid is not a fragment of type VII collagen. Author(s): Liu Y, Shimizu H, Hashimoto T. Source: Journal of Dermatological Science. 2003 August; 32(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850304

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Impact of laminin 5 beta3 gene versus protein replacement on gene expression patterns in junctional epidermolysis bullosa. Author(s): Robbins PB, Sheu SM, Goodnough JB, Khavari PA. Source: Human Gene Therapy. 2001 July 20; 12(11): 1443-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485635

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Impaired secretory immunity in dystrophic epidermolysis bullosa. Author(s): Sweet SP, Ballsdon AE, Harris JC, Roberts GJ, Challacombe SJ. Source: Oral Microbiology and Immunology. 1999 October; 14(5): 316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551159

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In this issue: The complexities of epidermolysis bullosa "simplex". Author(s): Paller AS. Source: The Journal of Investigative Dermatology. 2004 January; 122(1): Vi-Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962116

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Inflammatory variant of epidermolysis bullosa acquisita with IgG autoantibodies against type VII collagen and laminin alpha3. Author(s): Jonkman MF, Schuur J, Dijk F, Heeres K, de Jong MC, van der Meer JB, Yancey KB, Pas HH. Source: Archives of Dermatology. 2000 February; 136(2): 227-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10677099

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Inherited epidermolysis bullosa comes into the new millenium: a revised classification system based on current knowledge of pathogenetic mechanisms and the clinical, laboratory, and epidemiologic findings of large, well-defined patient cohorts. Author(s): Fine JD, McGrath J, Eady RA. Source: Journal of the American Academy of Dermatology. 2000 July; 43(1 Pt 1): 135-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10863241

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Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. Author(s): Ortiz-Urda S, Lin Q, Green CL, Keene DR, Marinkovich MP, Khavari PA. Source: The Journal of Clinical Investigation. 2003 January; 111(2): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531881

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Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita. Author(s): Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Source: Cochrane Database Syst Rev. 2003; (1): Cd004056. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535507

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Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquisita: a systematic literature review. Author(s): Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Source: Archives of Dermatology. 2002 March; 138(3): 380-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11902989

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Intracellular expression of type VII collagen during wound healing in severe recessive dystrophic epidermolysis bullosa and normal human skin. Author(s): McGrath JA, Leigh IM, Eady RA. Source: The British Journal of Dermatology. 1992 October; 127(4): 312-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1419750

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Intravenous iron (III) hydroxide-sucrose complex for anaemia in epidermolysis bullosa. Author(s): Atherton DJ, Cox I, Hann I. Source: The British Journal of Dermatology. 1999 April; 140(4): 773. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233353

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Is screening of the candidate gene necessary in unrelated partners of members of families with Herlitz junctional epidermolysis bullosa? Author(s): Klausegger A, Pulkkinen L, Pohla-Gubo G, Dallinger G, Puttinger R, Uitto J, Hintner H, Bauer JW. Source: The Journal of Investigative Dermatology. 2001 March; 116(3): 474-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231327

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Isolated nail dystrophy suggestive of dominant dystrophic epidermolysis bullosa. Author(s): Tosti A, Piraccini BM, Scher RK. Source: Pediatric Dermatology. 2003 September-October; 20(5): 456-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521572

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Japanese guidelines for diagnosis and treatment of junctional and dystrophic epidermolysis bullosa. Author(s): Tamai K, Hashimoto I, Hanada K, Ikeda S, Imamura S, Ogawa H; Japanese Study Group for Rare Intractable Skin Diseases. Source: Archives of Dermatological Research. 2003 April; 295 Suppl 1: S24-8. Epub 2003 March 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677429

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Junctional epidermolysis bullosa and pyloric atresia: a distinct entity. Clinical and pathological studies in five patients. Author(s): Valari MD, Phillips RJ, Lake BD, Harper JI. Source: The British Journal of Dermatology. 1995 November; 133(5): 732-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555025

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Junctional epidermolysis bullosa associated with congenital localized absence of skin, and pyloric atresia in two newborn siblings. Author(s): Puvabanditsin S, Garrow E, Kim DU, Tirakitsoontorn P, Luan J. Source: Journal of the American Academy of Dermatology. 2001 February; 44(2 Suppl): 330-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11174408

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Junctional epidermolysis bullosa gravis (Herlitz): diagnostic and genetic aspects. Author(s): Hauschild R, Wollina U, Bruckner-Tuderman L. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 January; 15(1): 73-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451332

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Junctional epidermolysis bullosa in a young patient. Author(s): Irak I, Soll SM, Camacho JM. Source: Journal of Pediatric Ophthalmology and Strabismus. 2003 May-June; 40(3): 1689. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12795439

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Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families. Author(s): Nakano A, Lestringant GG, Paperna T, Bergman R, Gershoni R, Frossard P, Kanaan M, Meneguzzi G, Richard G, Pfendner E, Uitto J, Pulkkinen L, Sprecher E. Source: Journal of the American Academy of Dermatology. 2002 April; 46(4): 510-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907499

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Junctional epidermolysis bullosa in the neonate: a case report. Author(s): Silverberg M, Fan-Paul N, Kane S, Medow N. Source: Journal of Pediatric Ophthalmology and Strabismus. 1999 July-August; 36(4): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442731

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Junctional epidermolysis bullosa lethalis with pyloric and anorectal obstruction. Author(s): Gahukamble DB, Gahukamble LD. Source: Pediatric Surgery International. 2001 July; 17(5-6): 472-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527195

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Junctional epidermolysis bullosa of the larynx. Author(s): Gonzalez A, Schachner L, Miller M. Source: Pediatrics. 1987 June; 79(6): 1051-2. Erratum In: Pediatrics 1987 November; 80(5): 649. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3588131

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Junctional epidermolysis bullosa of the larynx. Report of a case and literature review. Author(s): Berson S, Lin AN, Ward RF, Carter DM. Source: The Annals of Otology, Rhinology, and Laryngology. 1992 October; 101(10): 8615. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1416642

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Junctional epidermolysis bullosa with pyloric atresia: A case with favourable outcome. Author(s): Ha D, Idikio H, Krol A, Lin AN. Source: Journal of Cutaneous Medicine and Surgery. 1998 October; 3(2): 102-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9822785

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Junctional epidermolysis bullosa with pyloric stenosis presenting with electron microscopic findings suggestive of epidermolysis bullosa simplex. Author(s): Wasel N, Idikio H, Lees G, Krol A, Lin AN. Source: Pediatric Dermatology. 2000 September-October; 17(5): 395-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11085671

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Junctional epidermolysis bullosa with pyloric stenosis. Author(s): Morrell DS, Fine JD. Source: Pediatric Dermatology. 2001 November-December; 18(6): 539-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11841649

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Junctional epidermolysis bullosa: diagnosis and management of a patient with the Herlitz variant. Author(s): Goldstein AM, Davenport T, Sheridan RL. Source: Journal of Pediatric Surgery. 1998 May; 33(5): 756-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607491

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K5 D328E: a novel missense mutation in the linker 12 domain of keratin 5 associated with epidermolysis bullosa simplex (Weber-Cockayne). Author(s): Liovic M, Podrumac B, Dragos V, Vouk K, Komel R. Source: Human Heredity. 2000 July-August; 50(4): 234-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10782015

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Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's junctional epidermolysis bullosa patients. Author(s): Meneguzzi G, Marinkovich MP, Aberdam D, Pisani A, Burgeson R, Ortonne JP. Source: Experimental Dermatology. 1992 December; 1(5): 221-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1365323

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Keratin 14 gene mutations in patients with epidermolysis bullosa simplex. Author(s): Chen H, Bonifas JM, Matsumura K, Ikeda S, Leyden WA, Epstein EH Jr. Source: The Journal of Investigative Dermatology. 1995 October; 105(4): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7561171

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Keratin 14 gene point mutation in the Kobner and Dowling-Meara types of epidermolysis bullosa simplex as detected by the PASA method. Author(s): Hachisuka H, Morita M, Karashima T, Sasai Y. Source: Archives of Dermatological Research. 1995; 287(2): 142-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7539246

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Keratin 14 point mutations at codon 119 of helix 1A resulting in different epidermolysis bullosa simplex phenotypes. Author(s): Cummins RE, Klingberg S, Wesley J, Rogers M, Zhao Y, Murrell DF. Source: The Journal of Investigative Dermatology. 2001 November; 117(5): 1103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11710919

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Keratin clumping in epidermolysis bullosa, Dowling-Meara type. Author(s): Anton-Lamprecht I. Source: The British Journal of Dermatology. 1996 January; 134(1): 184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8745915

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Keratin mutations of epidermolysis bullosa simplex alter the kinetics of stress response to osmotic shock. Author(s): D'Alessandro M, Russell D, Morley SM, Davies AM, Lane EB. Source: Journal of Cell Science. 2002 November 15; 115(Pt 22): 4341-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376565

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Keratinocyte grafting in epidermolysis bullosa. Author(s): Bauer EA. Source: Journal of the American Academy of Dermatology. 1987 August; 17(2 Pt 1): 3001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2442209

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Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor-beta. Author(s): Konig A, Lauharanta J, Bruckner-Tuderman L. Source: The Journal of Investigative Dermatology. 1992 December; 99(6): 808-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1281864

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Keratinocytes from junctional epidermolysis bullosa do adhere and migrate on the basement membrane protein nicein through alpha 3 beta 1 integrin. Author(s): Verrando P, Lissitzky JC, Sarret Y, Winberg JO, Gedde-Dahl T Jr, Schmitt D, Bruckner-Tuderman L. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1994 October; 71(4): 567-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7967512

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LAMB3 gene transfection into SV40-transformed keratinocytes from patient with Herlitz junctional epidermolysis bullosa. Author(s): Masunaga T, Shimizu H, Matsui C, Aozaki R, Morohashi M, Yasumoto S, Nishikawa T. Source: Archives of Dermatological Research. 2000 April; 292(4): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10836613

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Laminin 5 mutations in junctional epidermolysis bullosa: molecular basis of Herlitz vs. non-Herlitz phenotypes. Author(s): Nakano A, Chao SC, Pulkkinen L, Murrell D, Bruckner-Tuderman L, Pfendner E, Uitto J. Source: Human Genetics. 2002 January; 110(1): 41-51. Epub 2001 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810295

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Large melanocytic nevi in hereditary epidermolysis bullosa. Author(s): Bauer JW, Schaeppi H, Kaserer C, Hantich B, Hintner H. Source: Journal of the American Academy of Dermatology. 2001 April; 44(4): 577-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260529

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Laryngeal epidermolysis bullosa acquisita requiring tracheostomy presenting with an acquired factor VIII coagulopathy. Author(s): Hurley D, Boyd JH, Eby C. Source: Otolaryngology and Head and Neck Surgery. 2001 September; 125(3): 270-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555765

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Letter: Glutaraldehyde therapy for epidermolysis bullosa. Author(s): Gordon HH. Source: Archives of Dermatology. 1974 August; 110(2): 297-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4212131

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Leukocytoclastic vasculitis in a child with epidermolysis bullosa simplex. Author(s): Sezgin G, Ceyhan M, Secmeer G, Bakkaloglu A, Kanra G, Buyukkale G. Source: Turk J Pediatr. 1999 April-June; 41(2): 277-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10770671

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Life-long course and molecular characterization of the original Dutch family with epidermolysis bullosa simplex with muscular dystrophy due to a homozygous novel plectin point mutation. Author(s): Koss-Harnes D, Hoyheim B, Jonkman MF, de Groot WP, de Weerdt CJ, Nikolic B, Wiche G, Gedde-Dahl T Jr. Source: Acta Dermato-Venereologica. 2004; 84(2): 124-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15206692

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Localized epidermolysis bullosa. Report of two cases and evaluation of therapy with glutaraldehyde. Author(s): DesGroseilliers JP, Brisson P. Source: Archives of Dermatology. 1974 January; 109(1): 70-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4203339

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Long-range polymerase chain reaction for specific full-length amplification of the human keratin 14 gene and novel keratin 14 mutations in epidermolysis bullosa simplex patients. Author(s): Wood P, Baty DU, Lane EB, McLean WH. Source: The Journal of Investigative Dermatology. 2003 March; 120(3): 495-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603865

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Lyophilised polyurethane membrane dressing for surgically-separated pseudosyndactyly in epidermolysis bullosa. Author(s): Cetin C, Kose AA, Karabagli Y, Ozyilmaz M. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 2003; 37(4): 245-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582761

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Major surgery and anesthetic technique in epidermolysis bullosa. Author(s): Komurcu M, Bilgin F, Kurt E, Atesalp AS. Source: Military Medicine. 2004 February; 169(2): 125-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040633

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Management of epidermolysis bullosa in infants and children. Author(s): Bello YM, Falabella AF, Schachner LA. Source: Clinics in Dermatology. 2003 July-August; 21(4): 278-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572698

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Management of esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Author(s): Castillo RO, Davies YK, Lin YC, Garcia M, Young H. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 May; 34(5): 535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12050581

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Management of generalized pruritus in dominant dystrophic epidermolysis bullosa using low-dose oral cyclosporin. Author(s): Calikoglu E, Anadolu R. Source: Acta Dermato-Venereologica. 2002; 82(5): 380-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12430742

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Molecular confirmation of the unique phenotype of epidermolysis bullosa simplex with mottled pigmentation. Author(s): Irvine AD, Rugg EL, Lane EB, Hoare S, Peret C, Hughes AE, Heagerty AH. Source: The British Journal of Dermatology. 2001 January; 144(1): 40-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167681

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Molecular consequences of deletion of the cytoplasmic domain of bullous pemphigoid 180 in a patient with predominant features of epidermolysis bullosa simplex. Author(s): Fontao L, Tasanen K, Huber M, Hohl D, Koster J, Bruckner-Tuderman L, Sonnenberg A, Borradori L. Source: The Journal of Investigative Dermatology. 2004 January; 122(1): 65-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962091

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Molecular diagnostics facilitate distinction between lethal and non-lethal subtypes of junctional epidermolysis bullosa: a case report and review of the literature. Author(s): Bauer J, Schumann H, Sonnichsen K, Tomaske M, Bosk A, BrucknerTuderman L, Rassner G, Garbe C. Source: European Journal of Pediatrics. 2002 December; 161(12): 672-9. Epub 2001 November 15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12447669

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Multicentric Castleman's disease associated with inherited epidermolysis bullosa. Author(s): Kawakami Y, Nishibu A, Kikuchi S, Ohtsuka M, Nakamura K, Nozawa Y, Abe M, Iwatsuki K, Kaneko F. Source: The Journal of Dermatology. 2003 September; 30(9): 689-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578560

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Mutation analysis of the entire keratin 5 and 14 genes in patients with epidermolysis bullosa simplex and identification of novel mutations. Author(s): Schuilenga-Hut PH, Vlies P, Jonkman MF, Waanders E, Buys CH, Scheffer H. Source: Human Mutation. 2003 April; 21(4): 447. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655565

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Mycophenolate mofetil in epidermolysis bullosa acquisita. Author(s): Kowalzick L, Suckow S, Ziegler H, Waldmann T, Ponnighaus JM, Glaser V. Source: Dermatology (Basel, Switzerland). 2003; 207(3): 332-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571084

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Non-Herlitz junctional epidermolysis bullosa without hair involvement associated with BP180 deficiency. Author(s): Guerriero C, De Simone C, Venier A, Rotoli M, Posteraro P, Zambruno G, Amerio P. Source: Dermatology (Basel, Switzerland). 2001; 202(1): 58-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11244233

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Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone. Author(s): Woodley DT, Krueger GG, Jorgensen CM, Fairley JA, Atha T, Huang Y, Chan L, Keene DR, Chen M. Source: The Journal of Investigative Dermatology. 2003 November; 121(5): 1021-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708601

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Normal expression of the 19-DEJ-1 epitope in two siblings with late-onset junctional epidermolysis bullosa. Author(s): Stouthamer A, Nieboer C, van der Waal RI, Jonkman MF. Source: The British Journal of Dermatology. 2001 May; 144(5): 1054-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359397

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Normal molecular weight of type VII collagen produced by recessive dystrophic epidermolysis bullosa keratinocytes. Author(s): Jenison M, Fine JD, Gammon WR, O'Keefe EJ. Source: The Journal of Investigative Dermatology. 1993 January; 100(1): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8423408

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Novel and recurrent mutations in the integrin beta 4 subunit gene causing lethal junctional epidermolysis bullosa with pyloric atresia. Author(s): Iacovacci S, Cicuzza S, Odorisio T, Silvestri E, Kayserili H, Zambruno G, Puddu P, D'Alessio M. Source: Experimental Dermatology. 2003 October; 12(5): 716-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705814

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Novel KRT14 mutation in a Taiwanese patient with epidermolysis bullosa simplex (Kobner type). Author(s): Chao SC, Yang MH, Lee SF. Source: J Formos Med Assoc. 2002 April; 101(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101866

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Novel mechanism of revertant mosaicism in Dowling-Meara epidermolysis bullosa simplex. Author(s): Smith FJ, Morley SM, McLean WH. Source: The Journal of Investigative Dermatology. 2004 January; 122(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962092

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Novel mutations in the LAMC2 gene in non-Herlitz junctional epidermolysis bullosa: effects on laminin-5 assembly, secretion, and deposition. Author(s): Castiglia D, Posteraro P, Spirito F, Pinola M, Angelo C, Puddu P, Meneguzzi G, Zambruno G. Source: The Journal of Investigative Dermatology. 2001 September; 117(3): 731-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11564184

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Novel premature termination codon mutations in the laminin gamma2-chain gene (LAMC2) in Herlitz junctional epidermolysis bullosa. Author(s): Takizawa Y, Shimizu H, Pulkkinen L, Nonaka S, Kubo T, Kado Y, Nishikawa T, Uitto J. Source: The Journal of Investigative Dermatology. 1998 December; 111(6): 1233-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856849

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Nutrition in dystrophic epidermolysis bullosa. Author(s): Allman S, Haynes L, MacKinnon P, Atherton DJ. Source: Pediatric Dermatology. 1992 September; 9(3): 231-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1488371

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Oesophageal stricture in dystrophic epidermolysis bullosa--multiple dilatation with gruntzig balloon catheter. Author(s): Kumar N, Anand BS, Govil A, Chowdhury V. Source: Trop Gastroenterol. 1994 October-December; 15(4): 222-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7618205

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Optimal conditions of 1 M NaCl splitting technique to demonstrate basement membrane zone antigens in bullous pemphigoid, epidermolysis bullosa acquisita and linear IgA bullous dermatoses. Author(s): Jenkins RE, Rodenas J, Bhogal BS, Black MM. Source: Dermatology (Basel, Switzerland). 1994; 189 Suppl 1: 133-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8049556

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Oral and gastrointestinal manifestations of epidermolysis bullosa. Author(s): Travis SP, McGrath JA, Turnbull AJ, Schofield OM, Chan O, O'Connor AF, Mayou B, Eady RA, Thompson RP. Source: Lancet. 1992 December 19-26; 340(8834-8835): 1505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1361600

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Oral epidermolysis bullosa in adults. Author(s): Harel-Raviv M, Bernier S, Raviv E, Gornitsky M. Source: Spec Care Dentist. 1995 July-August; 15(4): 144-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9002917

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Oral involvement of recessive dystrophic epidermolysis bullosa inversa. Author(s): Wright JT, Fine JD, Johnson LB, Steinmetz TT. Source: American Journal of Medical Genetics. 1993 December 1; 47(8): 1184-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8291553

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Oral lesions in recessive dystrophic epidermolysis bullosa. Author(s): Serrano-Martinez MC, Bagan JV, Silvestre FJ, Viguer MT. Source: Oral Diseases. 2003 September; 9(5): 264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628894

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Oro-dental manifestations in Hallopeau-Siemens-type recessive dystrophic epidermolysis bullosa. Author(s): De Benedittis M, Petruzzi M, Favia G, Serpico R. Source: Clinical and Experimental Dermatology. 2004 March; 29(2): 128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987265

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Orthodontic management of a patient with epidermolysis bullosa. Author(s): Goldschmied F. Source: Aust Orthod J. 1999 November; 15(5): 302-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806937

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Osteoporosis in a patient with recessive dystrophic epidermolysis bullosa. Author(s): Kawaguchi M, Mitsuhashi Y, Kondo S. Source: The British Journal of Dermatology. 1999 November; 141(5): 934-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10583187

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Outcome after surgical repair of junctional epidermolysis bullosa-pyloric atresia syndrome: a report of 3 cases and review of the literature. Author(s): Dank JP, Kim S, Parisi MA, Brown T, Smith LT, Waldhausen J, Sybert VP. Source: Archives of Dermatology. 1999 October; 135(10): 1243-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10522673

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Paraneoplastic immunobullous disease with an epidermolysis bullosa acquisita phenotype: two cases demonstrating remission with treatment of gynaecological malignancy. Author(s): Chamberlain AJ, Cooper SM, Allen J, Dean D, Baxter KF, Goodfield MJ, Wojnarowska F. Source: The Australasian Journal of Dermatology. 2004 May; 45(2): 136-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068465

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Paternal germline mosaicism in Herlitz junctional epidermolysis bullosa. Author(s): Cserhalmi-Friedman PB, Anyane-Yeboa K, Christiano AM. Source: Experimental Dermatology. 2002 October; 11(5): 468-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366701

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Pathogenic mechanisms in epidermolysis bullosa naevi. Author(s): Lanschuetzer CM, Emberger M, Hametner R, Klausegger A, Pohla-Gubo G, Hintner H, Bauer JW. Source: Acta Dermato-Venereologica. 2003; 83(5): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609098

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Pharyngogastric colonic interposition for total oesophageal occlusion in epidermolysis bullosa. Author(s): Elton C, Marshall RE, Hibbert J, Cameron R, Mason RC. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(2): 175-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14601913

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PhiC31 integrase-mediated nonviral genetic correction of junctional epidermolysis bullosa. Author(s): Ortiz-Urda S, Thyagarajan B, Keene DR, Lin Q, Calos MP, Khavari PA. Source: Human Gene Therapy. 2003 June 10; 14(9): 923-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828862

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Placement of endosseous implants in patients with oral epidermolysis bullosa. Author(s): Penarrocha-Diago M, Serrano C, Sanchis JM, Silvestre FJ, Bagan JV. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2000 November; 90(5): 587-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11077381

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Pregnancy and cesarean delivery in a patient with dystrophic epidermolysis bullosa. Author(s): Bianca S, Reale A, Ettore G. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 October 10; 110(2): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969591

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Prenatal diagnosis for epidermolysis bullosa: a study of 144 consecutive pregnancies at risk. Author(s): Pfendner EG, Nakano A, Pulkkinen L, Christiano AM, Uitto J. Source: Prenatal Diagnosis. 2003 June; 23(6): 447-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12813757

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Progress in molecular genetics of heritable skin diseases: the paradigms of epidermolysis bullosa and pseudoxanthoma elasticum. Author(s): Uitto J, Pulkkinen L, Ringpfeil F. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 2002 December; 7(1): 6-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518787

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Pyloric atresia-junctional epidermolysis bullosa syndrome showing novel 594insC/Q425P mutations in integrin beta4 gene (ITGB4). Author(s): Masunaga T, Ishiko A, Takizawa Y, Kim SC, Lee JS, Nishikawa T, Shimizu H. Source: Experimental Dermatology. 2004 January; 13(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15009117

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Quality of life in epidermolysis bullosa. Author(s): Horn HM, Tidman MJ. Source: Clinical and Experimental Dermatology. 2002 November; 27(8): 707-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472552

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Rapid decay of alpha6 integrin caused by a mis-sense mutation in the propeller domain results in severe junctional epidermolysis bullosa with pyloric atresia. Author(s): Allegra M, Gagnoux-Palacios L, Gache Y, Roques S, Lestringant G, Ortonne JP, Meneguzzi G. Source: The Journal of Investigative Dermatology. 2003 December; 121(6): 1336-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675179

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Recessive dystrophic epidermolysis bullosa treated with phenytoin. Author(s): Abahussein AA, al-Zayir AA, Mostafa WZ, Okoro AN. Source: International Journal of Dermatology. 1992 October; 31(10): 730-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1399206

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Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens)--improvement of wound healing by autologous epidermal grafts on an esterified hyaluronic acid membrane. Author(s): Wollina U, Konrad H, Fischer T. Source: The Journal of Dermatology. 2001 April; 28(4): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11449673

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Recessive epidermolysis bullosa simplex phenotype reproduced in vitro: ablation of keratin 14 is partially compensated by keratin 17. Author(s): El Ghalbzouri A, Jonkman M, Kempenaar J, Ponec M. Source: American Journal of Pathology. 2003 November; 163(5): 1771-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578178

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Reduced expression of insulin-like growth factor-binding protein-3 (IGFBP-3) in Squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa. Author(s): Mallipeddi R, Wessagowit V, South AP, Robson AM, Orchard GE, Eady RA, McGrath JA. Source: The Journal of Investigative Dermatology. 2004 May; 122(5): 1302-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15140235

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Relative extent of skin involvement in inherited epidermolysis bullosa (EB): composite regional anatomic diagrams based on the findings of the National EB Registry, 1986 to 2002. Author(s): Devries DT, Johnson LB, Weiner M, Fine JD. Source: Journal of the American Academy of Dermatology. 2004 April; 50(4): 572-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15034506

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Renal amyloidosis in recessive dystrophic epidermolysis bullosa. Author(s): Kaneko K, Kakuta M, Ohtomo Y, Shimizu T, Yamashiro Y, Ogawa H, Manabe M. Source: Dermatology (Basel, Switzerland). 2000; 200(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828628

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Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa. Author(s): Chen M, Kasahara N, Keene DR, Chan L, Hoeffler WK, Finlay D, Barcova M, Cannon PM, Mazurek C, Woodley DT. Source: Nature Genetics. 2002 December; 32(4): 670-5. Epub 2002 November 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426566

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Reversible acute global left ventricular dysfunction in a patient with autosomal recessive dystrophic epidermolysis bullosa. Author(s): Morelli S, Dianzani C, Sgreccia A, Porciello R, Bottoni U, Calvieri S. Source: International Journal of Cardiology. 2001 July; 79(2-3): 321-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488288

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Revised classification system for inherited epidermolysis bullosa: Report of the Second International Consensus Meeting on diagnosis and classification of epidermolysis bullosa. Author(s): Fine JD, Eady RA, Bauer EA, Briggaman RA, Bruckner-Tuderman L, Christiano A, Heagerty A, Hintner H, Jonkman MF, McGrath J, McGuire J, Moshell A, Shimizu H, Tadini G, Uitto J. Source: Journal of the American Academy of Dermatology. 2000 June; 42(6): 1051-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10827412

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Severe palmo-plantar hyperkeratosis in Koebner epidermolysis bullosa simplex. Author(s): Shirakata Y, Tamai K, Nakaoka H, Tokumaru S, Sayama K, Murakami S, Hashimoto K. Source: The Journal of Dermatology. 2003 February; 30(2): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692381

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Simultaneous occurrence of three squamous cell carcinomas in a recessive dystrophic epidermolysis bullosa patient. Author(s): Tomita Y, Sato-Matsumura KC, Sawamura D, Matsumura T, Shimizu H. Source: Acta Dermato-Venereologica. 2003; 83(3): 225-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816163

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Skin bioequivalents and their role in the treatment of inherited epidermolysis bullosa. Author(s): Fine JD. Source: Archives of Dermatology. 2000 October; 136(10): 1259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030774

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Splice site mutation in the type VII collagen gene (COL7A1) in a Taiwanese family with recessive dystrophic epidermolysis bullosa. Author(s): Lin GT, Chen SK, Liu CS, Wang WH. Source: J Formos Med Assoc. 2000 September; 99(9): 693-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11000732

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Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeauSiemens recessive dystrophic epidermolysis bullosa. Author(s): Kawasaki H, Sawamura D, Iwao F, Kikuchi T, Nakamura H, Okubo S, Matsumura T, Shimizu H. Source: The British Journal of Dermatology. 2003 May; 148(5): 1047-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786841

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Squamous cell carcinoma in junctional and dystrophic epidermolysis bullosa. Author(s): Weber F, Bauer JW, Sepp N, Hogler W, Salmhofer W, Hintner H, Fritsch P. Source: Acta Dermato-Venereologica. 2001 June-July; 81(3): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11558875

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Sucralfate: a help during oral management in patients with epidermolysis bullosa. Author(s): Marini I, Vecchiet F. Source: J Periodontol. 2001 May; 72(5): 691-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11394407

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Surgical management of hand deformities in recessive dystrophic epidermolysis bullosa. Author(s): Zarem HA, Pearson RW, Leaf N. Source: British Journal of Plastic Surgery. 1974 April; 27(2): 176-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4601119

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Surgical treatment of recessive dystrophic epidermolysis bullosa in the hand: use of tissue-engineered skin (Apligraf). Author(s): Phillips J, Rockwell WB. Source: Annals of Plastic Surgery. 2003 April; 50(4): 441-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671394

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Sustainable correction of junctional epidermolysis bullosa via transposon-mediated nonviral gene transfer. Author(s): Ortiz-Urda S, Lin Q, Yant SR, Keene D, Kay MA, Khavari PA. Source: Gene Therapy. 2003 July; 10(13): 1099-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808440

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Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. Author(s): Meng X, Klement JF, Leperi DA, Birk DE, Sasaki T, Timpl R, Uitto J, Pulkkinen L. Source: The Journal of Investigative Dermatology. 2003 October; 121(4): 720-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632187

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Tetracycline and epidermolysis bullosa simplex: a double-blind, placebo-controlled, crossover randomized clinical trial. Author(s): Weiner M, Stein A, Cash S, de Leoz J, Fine JD. Source: The British Journal of Dermatology. 2004 March; 150(3): 613-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030362

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The carboxyl terminus of type VII collagen mediates antiparallel dimer formation and constitutes a new antigenic epitope for epidermolysis Bullosa acquisita autoantibodies. Author(s): Chen M, Keene DR, Costa FK, Tahk SH, Woodley DT. Source: The Journal of Biological Chemistry. 2001 June 15; 276(24): 21649-55. Epub 2001 March 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274208

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The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with crohn's disease have autoantibodies to type VII collagen. Author(s): Chen M, O'Toole EA, Sanghavi J, Mahmud N, Kelleher D, Weir D, Fairley JA, Woodley DT. Source: The Journal of Investigative Dermatology. 2002 June; 118(6): 1059-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060403

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The hand in recessive dystrophic epidermolysis bullosa. Author(s): Glicenstein J, Mariani D, Haddad R. Source: Hand Clin. 2000 November; 16(4): 637-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117053

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The P25L mutation in the KRT5 gene in a Japanese family with epidermolysis bullosa simplex with mottled pigmentation. Author(s): Hamada T, Ishii N, Kawano Y, Takahashi Y, Inoue M, Yasumoto S, Hashimoto T. Source: The British Journal of Dermatology. 2004 March; 150(3): 609-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030360

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Three cases of de novo dominant dystrophic epidermolysis bullosa associated with the mutation G2043R in COL7A1. Author(s): Wessagowit V, Ashton GH, Mohammedi R, Salas-Alanis JC, Denyer JE, Mellerio JE, Eady RA, McGrath JA. Source: Clinical and Experimental Dermatology. 2001 January; 26(1): 97-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260189

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Toward epidermal stem cell-mediated ex vivo gene therapy of junctional epidermolysis bullosa. Author(s): Dellambra E, Pellegrini G, Guerra L, Ferrari G, Zambruno G, Mavilio F, De Luca M. Source: Human Gene Therapy. 2000 November 1; 11(16): 2283-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084687

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Treatment of two patients with Herlitz junctional epidermolysis bullosa with artificial skin bioequivalents. Author(s): Jiang QJ, Izakovic J, Zenker M, Fartasch M, Meneguzzi G, Rascher W, Schneider H. Source: The Journal of Pediatrics. 2002 October; 141(4): 553-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12378197

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Type XVII collagen gene mutations in junctional epidermolysis bullosa and prospects for gene therapy. Author(s): Bauer JW, Lanschuetzer C. Source: Clinical and Experimental Dermatology. 2003 January; 28(1): 53-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558632

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Ulcers in pretibial epidermolysis bullosa. Grafting with autologous meshed splitthickness skin and allogeneic cultured keratinocytes. Author(s): Beele H, Naeyaert JM, Monstrey S, Kint A. Source: Archives of Dermatology. 1995 September; 131(9): 990-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7661624

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Ultrastructural differentiation of epidermolysis bullosa subtypes and porphyria cutanea tarda. Author(s): Jaunzems AE, Woods AE. Source: Pathology, Research and Practice. 1997; 193(3): 207-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9198106

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Ultrastructural features of epidermolysis bullosa. Author(s): Hanna W, Silverman E, Boxall L, Krafchik BR. Source: Ultrastructural Pathology. 1983 July; 5(1): 29-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6649087

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Ultrastructural findings in epidermolysis bullosa. Author(s): Smith LT. Source: Archives of Dermatology. 1993 December; 129(12): 1578-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7504435

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Uncommon disorders. Epidermolysis bullosa. Author(s): MacKinnon P. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1991 October 23-29; 6(5): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1760318

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Upper airway and external genital involvement in epidermolysis bullosa dystrophica. Author(s): Shackelford GD, Bauer EA, Graviss ER, McAlister WH. Source: Radiology. 1982 May; 143(2): 429-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7071344

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Urinary chondroitin of epidermolysis bullosa cystrophica et albo-papuloidea (Pasini). Author(s): Endo M, Yamamoto R, Yosizawa Z, Sasai Y, Saito N. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1974 December 17; 57(3): 249-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4434645

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Use of a permanent acellular dermal allograft in recessive dystrophic epidermolysis bullosa involving the hands. Author(s): Witt PD, Cohen DT, Mallory SB. Source: Archives of Dermatology. 1999 May; 135(5): 503-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10328187

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Use of a subcutaneous syringe driver in epidermolysis bullosa. Author(s): O'Neill B, Lucas C, Gannon C. Source: Palliative Medicine. 2001 January; 15(1): 77-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11212474

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Use of type VII collagen gene (COL7A1) markers in prenatal diagnosis of recessive dystrophic epidermolysis bullosa. Author(s): Dunnill MG, Rodeck CH, Richards AJ, Atherton D, Lake BD, Petrou M, Eady RA, Pope FM. Source: Journal of Medical Genetics. 1995 September; 32(9): 749-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8544200

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Vaginal agglutination and hematometra associated with epidermolysis bullosa. Author(s): Steinkampf MP, Reilly SD, Ackerman GE. Source: Obstetrics and Gynecology. 1987 March; 69(3 Pt 2): 519-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3808539

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Verruciform xanthoma. Occurrence in eroded skin in a patient with recessive dystrophic epidermolysis bullosa. Author(s): Cooper TW, Santa Cruz DJ, Bauer EA. Source: Journal of the American Academy of Dermatology. 1983 April; 8(4): 463-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6853779

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Very late antigen (VLA) expression in various forms of epidermolysis bullosa simplex. Author(s): Nazzaro V, Berti E, Cavalli R, Brusasco A, Caputo R. Source: Archives of Dermatological Research. 1991; 283(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2059055

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Vitamin E and epidermolysis bullosa. Author(s): Ayres S Jr, Mihan R. Source: Dermatologica. 1973; 146(1): 61. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4694143

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Vitamin E therapy in dystrophic epidermolysis bullosa. Author(s): Sehgal VN, Sanyal RK. Source: Archives of Dermatology. 1972 March; 105(3): 460. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5012154

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Vitamin E treatment of epidermolysis bullosa acquisita. Author(s): Rosten M. Source: The Australasian Journal of Dermatology. 1976 August; 17(2): 52-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1022216

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Vitamin E treatment of epidermolysis bullosa. Changes in tissue collagenase levels. Author(s): Michaelson JD, Schmidt JD, Dresden MH, Duncan WC. Source: Archives of Dermatology. 1974 January; 109(1): 67-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4358395

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Wound healing and epidermolysis bullosa. Author(s): Carter DM, Lin AN. Source: Archives of Dermatology. 1988 May; 124(5): 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3129995

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X-linked epidermolysis bullosa (Mendes da Costa), poikiloderma, retarded growth. Author(s): Pegum JS, Ramsay CA. Source: Proc R Soc Med. 1973 March; 66(3): 234-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4266844

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CHAPTER 2. NUTRITION AND EPIDERMOLYSIS BULLOSA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and epidermolysis bullosa.

Finding Nutrition Studies on Epidermolysis Bullosa 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 “epidermolysis bullosa” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

A case of nonscarring inflammatory epidermolysis bullosa acquisita: characterization of IgG autoantibodies by immunofluorescence, immunoblotting and immunogold electron microscopy. Author(s): Department of Dermatology, Nara Medical University, Japan. Source: Honoki, K Muramatsu, T Nakatani, C Iida, T Shirai, T J-Dermatol. 1998 October; 25(10): 666-72 0385-2407

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A novel mutation in the L12 domain of keratin 5 in the Kobner variant of epidermolysis bullosa simplex. Author(s): Department of Biochemistry and the Center for Molecular and Cellular Biology, University of Queensland, Brisbane, Australia. Source: Galligan, P Listwan, P Siller, G M Rothnagel, J A J-Invest-Dermatol. 1998 September; 111(3): 524-7 0022-202X

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A novel variant of acquired epidermolysis bullosa with autoantibodies against the central triple-helical domain of type VII collagen. Author(s): Department of Dermatology, Asahikawa Medical College, Japan. Source: Tanaka, H Ishida Yamamoto, A Hashimoto, T Hiramoto, K Harada, T Kawachi, Y Shimizu, H Tanaka, T Kishiyama, K Hopfner, B Takahashi, H Iizuka, H Bruckner Tuderman, L Lab-Invest. 1997 December; 77(6): 623-32 0023-6837

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Aluminum chloride hexahydrate and blistering in epidermolysis bullosa simplex. Author(s): University Department of Dermatology, Royal Infirmary of Edinburgh, Scotland. Source: Younger, I R Priestley, G C Tidman, M J J-Am-Acad-Dermatol. 1990 November; 23(5 Pt 1): 930-1 0190-9622

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Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis, and immunopathology in 11 children. Author(s): Department of Dermatology, Oxford Radcliffe Hospital, England. Source: Edwards, S Wakelin, S H Wojnarowska, F Marsden, R A Kirtschig, G Bhogal, B Black, M M Pediatr-Dermatol. 1998 May-June; 15(3): 184-90 0736-8046

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Clearing of epidermolysis bullosa acquisita with cyclosporine. Author(s): Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27514. Source: Crow, L L Finkle, J P Gammon, W R Woodley, D T J-Am-Acad-Dermatol. 1988 November; 19(5 Pt 2): 937-42 0190-9622

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Colchicine for epidermolysis bullosa acquisita. Author(s): Department of Dermatology, Stanford University Medical School, Palo Alto, California, USA. Source: Cunningham, B B Kirchmann, T T Woodley, D J-Am-Acad-Dermatol. 1996 May; 34(5 Pt 1): 781-4 0190-9622

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Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa letalis. Author(s): Paolo Periolo Centre for Neuromuscular Diseases, University of Turin, Italy. Source: Doriguzzi, C Palmucci, L Mongini, T Bertolotto, A Maniscalco, M Chiado Piat, L Zina, A M Bundino, S Eur-Neurol. 1993; 33(6): 454-60 0014-3022

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Correction of the anemia of epidermolysis bullosa with intravenous iron and erythropoietin. Author(s): Department of Hematology/Oncology, Children's Hospital Oakland, California 94609, USA. Source: Fridge, J L Vichinsky, E P J-Pediatr. 1998 May; 132(5): 871-3 0022-3476

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Cytofluorometric study of lectin binding to the keratinocytes of epidermolysis bullosa simplex. Author(s): Department of Dermatology, Kurume University School of Medicine, Japan. Source: Hachisuka, H Nomura, H Sakamoto, F Sasai, Y Acta-Histochem. 1990; 89(1): 85-9 0065-1281

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Death from metastatic, cutaneous, squamous cell carcinoma in autosomal recessive dystrophic epidermolysis bullosa despite permanent inpatient care. Author(s): Department of Dermatology, Stobhill General Hospital, Glasgow, Scotland. Source: Keefe, M Wakeel, R A Dick, D C Dermatologica. 1988; 177(3): 180-4 0011-9075

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Emerging treatment for epidermolysis bullosa acquisita. Author(s): Department of Medicine, New England Baptist Hospital, and the Department of Oral Medicine, Harvard School of Dental Medicine, Boston, MA, USA. Source: Engineer, L Ahmed, A R J-Am-Acad-Dermatol. 2001 May; 44(5): 818-28 01909622

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High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the Cockayne-Touraine type. Author(s): Department of Dermatology, University of Ehime School of Medicine, Japan. Source: Shirakata, Y Shiraishi, S Sayama, K Shinmori, H Miki, Y J-Dermatol. 1993 November; 20(11): 723-5 0385-2407

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Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities. Author(s): Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10021-6399. Source: Krueger, J G Lin, A N Leong, I Carter, D M J-Invest-Dermatol. 1991 November; 97(5): 849-61 0022-202X

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Management of oesophageal stenosis in epidermolysis bullosa dystrophica. Author(s): Prince of Wales Children's Hospital, Australia. Source: Kern, I B Eisenberg, M Willis, S Arch-Dis-Child. 1989 April; 64(4): 551-6 00039888

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Treatment of junctional epidermolysis bullosa with epidermal autografts. Source: Carter, D M Lin, A N Varghese, M C Caldwell, D Pratt, L A Eisinger, M J-AmAcad-Dermatol. 1987 August; 17(2 Pt 1): 246-50 0190-9622

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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3.

ALTERNATIVE MEDICINE EPIDERMOLYSIS BULLOSA

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to epidermolysis bullosa. 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 epidermolysis bullosa 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 “epidermolysis bullosa” (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 epidermolysis bullosa: •

Blister fluid from epidermolysis bullosa letalis induces dermal-epidermal separation in vitro. Author(s): Matsumoto M, Hashimoto K. Source: The Journal of Investigative Dermatology. 1986 July; 87(1): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3722859

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Care of epidermolysis bullosa patients: a nursing challenge. Author(s): Gibbons S. Source: Dermatology Nursing / Dermatology Nurses' Association. 1990 August; 2(4): 195-200, 214. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2144433

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Care of the hand in recessive epidermolysis bullosa. Author(s): Greider JL Jr, Flatt AE. Source: Plastic and Reconstructive Surgery. 1983 August; 72(2): 222-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6348818

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Chronic wound caring. a long journey toward healing. Author(s): Orsted HL, Campbell KE, Keast DH, Coutts P, Sterling W. Source: Ostomy Wound Manage. 2001 October; 47(10): 26-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11890076

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Comparative study of autoantigens for various bullous skin diseases by immunoblotting using different dermo-epidermal separation techniques. Author(s): Ohata Y, Hashimoto T, Nishikawa T. Source: Clinical and Experimental Dermatology. 1995 November; 20(6): 454-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8857335

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Cytofluorometric study of lectin binding to the keratinocytes of epidermolysis bullosa simplex. Author(s): Hachisuka H, Nomura H, Sakamoto F, Sasai Y. Source: Acta Histochemica. 1990; 89(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2127148

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Dilated cardiomyopathy complicating a case of epidermolysis bullosa dystrophica. Author(s): Brook MM, Weinhouse E, Jarenwattananon M, Nudel DB. Source: Pediatric Dermatology. 1989 March; 6(1): 21-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2704658

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Epidermolysis bullosa. Assessment of a treatment regimen. Author(s): Haber RM, Ramsay CA, Boxall LB. Source: International Journal of Dermatology. 1985 June; 24(5): 324-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4018985

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High-dose tocopherol acetate therapy in epidermolysis bullosa siblings of the Cockayne-Touraine type. Author(s): Shirakata Y, Shiraishi S, Sayama K, Shinmori H, Miki Y. Source: The Journal of Dermatology. 1993 November; 20(11): 723-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8300945

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In vivo restoration of laminin 5 beta 3 expression and function in junctional epidermolysis bullosa. Author(s): Robbins PB, Lin Q, Goodnough JB, Tian H, Chen X, Khavari PA.

Alternative Medicine 81

Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 April 24; 98(9): 5193-8. Epub 2001 Apr 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296269 •

Living with epidermolysis bullosa. Author(s): Eisenberg R. Source: Lamp. 1981 September; 38(9): 38-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6913745

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Origin and properties of the blister formation factor in blister fluids from recessive dystrophic epidermolysis bullosa. Author(s): Ikeda S, Naito K, Imai R, Manabe M, Takamori K, Ogawa H. Source: The British Journal of Dermatology. 1985 December; 113(6): 661-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4096882

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Practical and psychological problems for parents of children with epidermolysis bullosa. Author(s): Lansdown R, Atherton D, Dale A, Sproston S, Lloyd J. Source: Child: Care, Health and Development. 1986 July-August; 12(4): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3742737

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Proteases are responsible for blister formation in recessive dystrophic epidermolysis bullosa and epidermolysis bullosa simplex. Author(s): Takamori K, Ikeda S, Naito K, Ogawa H. Source: The British Journal of Dermatology. 1985 May; 112(5): 533-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3890916

•

Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression. Author(s): McGrath JA, Ishida-Yamamoto A, O'Grady A, Leigh IM, Eady RA. Source: The Journal of Investigative Dermatology. 1993 April; 100(4): 366-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8454899

•

Sunbed-induced pseudoporphyria. Author(s): Murphy GM, Wright J, Nicholls DS, McKee PH, Messenger AG, Hawk JL, Levene GM. Source: The British Journal of Dermatology. 1989 April; 120(4): 555-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2730845

•

The role of divalent cations in epidermolysis. Author(s): Dimond RL, Erickson KL, Wuepper KD.

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Source: The British Journal of Dermatology. 1976 July; 95(1): 25-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8071 •

Therapeutic value of large doses of vitamin E in epidermolysis bullosa acquisita. Author(s): Ayres S Jr, Mihan R. Source: The Australasian Journal of Dermatology. 1972 December; 13(3): 140. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4664567

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/

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

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CHAPTER 4. PATENTS ON EPIDERMOLYSIS BULLOSA 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 “epidermolysis bullosa” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on epidermolysis bullosa, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Epidermolysis Bullosa By performing a patent search focusing on epidermolysis bullosa, 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. 8Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on epidermolysis bullosa: •

Hydroxamic acid tetrapeptide derivatives Inventor(s): Morikawa; Tadanori (Toyama, JP), Nagai; Yutaka (Koshigaya, JP), Obata; Masami (Toyama, JP), Odake; Shinjiro (Takaoka, JP), Okayama; Toru (Ishikawa, JP) Assignee(s): Fuji Yakuhin Kogyo Kabushiki Kaisha (Toyama, JP) Patent Number: 5,100,874 Date filed: August 4, 1989 Abstract: New peptide derivatives of which utility in the treatment of such diseases as rheumatoid arthritis, peridental diseases, corneal ulcer and epidermolysis bullosa is expected. These compounds are hydroxamic acid derivatives of tetrapeptides having a specific inhibitory activity against collagenase derived from vertebrates. Excerpt(s): The present invention relates to new peptidylhydroxamic acid derivatives which specifically inhibit the action of collagenase of vertebrate origin, as well as to collagenase inhibitors containing these new peptidylhydroxamic acid derivatives as active ingredient. Collagenase is an enzyme which decomposes collagen, one of the main protein components constituting connective tissues. Animals in pathological conditions show an abnormal overaction of collagenase in processes of the destruction and repair of tissues. Such abnormal overaction of collagenase is observed, for example, in such cases as rheumatoid arthritis, peridental diseases, corneal ulcer and epidermolysis bullosa, where inhibition of the action of collagenase provides a useful means for treating such diseases. Web site: http://www.delphion.com/details?pn=US05100874__

•

Methods for treatment of inflammatory diseases Inventor(s): Farber; Elliott (North Mankato, MN) Assignee(s): Alwyn Company, Inc. (Lake Crystal, MN) Patent Number: 6,673,826 Date filed: January 11, 2001 Abstract: An improved method of treating skin diseases comprises applying to the skin of a patient suffering such a skin disease an allantoin-containing composition in a therapeutically effective quantity. The allantoin-containing composition is a water-in-oil emulsion that includes allantoin and an emulsifier system that includes at least one emulsifier that is either an anionic emulsifier or a nonionic emulsifier. If the emulsifier is an anionic emulsifier, the emulsifier system can include beeswax. The nonionic emulsifiers used can include at least one nonionic emulsifier that is an ethoxylated ether or an ethoxylated ester whose carbon chain length ranges from 8 to 22 carbon atoms. Alternatively, the emulsifier system can include an acidic anionic polymer such as carboxypolymethylene and an anionic emulsifier. In another alternative, the emulsifier system can include the acidic anionic polymer and a nonionic emulsifier, or the acidic anionic polymer alone. In still another alternative, the emulsifier system can include cetyl alcohol and stearic acid. In yet another alternative, the emulsifier system can include sodium stearoyl lactylate and sodium isostearoyl lactylate. In another alternative, the emulsifier system can include at least one polyethyleneglycol ether of

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cetearyl alcohol. In still another alternative, the emulsifier system can include a polyethylene glycol ester of stearic acid and glyceryl stearate. The composition can include other ingredients. The pH of the composition used in a method according to the present invention is from about 3.0 to about 6.0; preferably, a narrower pH range is used, varying with each embodiment of the composition. Among the diseases that can be treated is epidermolysis bullosa. Excerpt(s): The present invention is directed to improved methods of treating inflammatory skin disease. Inflammatory skin disease, particularly chronic inflammatory skin disease, is still a major source of morbidity. Such inflammatory skin diseases are disfiguring and cause severe physical and psychological harm to patients, disrupting their quality of life substantially. Such diseases include decubitus ulcers, pressure ulcers, diabetic ulcers, epidermolysis bullosa, and milia. Such skin diseases tend to be chronic and difficult to treat, particularly in patients with poor circulation or other underlying disease states. Among the most difficult of these diseases to treat is epidermolysis bullosa. Epidermolysis bullosa occurs in newborns and infants and causes severe inflammation, blistering, and scarring. Web site: http://www.delphion.com/details?pn=US06673826__

Patent Applications on Epidermolysis Bullosa 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 epidermolysis bullosa: •

Isolation of the lamin gamma2 gene in horses and its use in diagnostic junctional epidermolysis bullosa Inventor(s): Baird, John; (Guelph, CA), Charlesworth, Alexandra; (Nice, FR), Linder, Keith; (Raleigh, NC), Meneguzzi, Guerrino; (Nice, FR), Spirito, Flavia; (Nice, FR) Correspondence: Ogilvy Renault; 1981 Mcgill College Avenue; Suite 1600; Montreal; QC; H3a2y3; CA Patent Application Number: 20030143545 Date filed: January 24, 2002 Abstract: The laminin.gamma.2 subunit of equine laminin-5 gene has been cloned and the nucleic acid and corresponding protein amino acid sequence is provided. A method of diagnosing junctional epidermolysis bullosa in horses is also provided based on the determination that a mutation in the laminin.gamma.2 gene in which a cytosine is inserted at position 1368 is associated with the disease. Excerpt(s): The present invention relates to the isolation of the gene encoding the.gamma.2 subunit of equine laminin-5 and its use in diagnosing junctional epidermolysis bullosa (JEB) in horses. Epidermolysis bullosa (EB) is a group of hereditary and acquired diseases of the skin and mucous membranes that share the common feature of the formation of blisters and erosions in response to minor trauma (Fine et al., 2000). In humans, the clinical forms of hereditary EB are divided into three main categories, each typified by the level of skin separation within the dermal-

9

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

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epidermal basement membrane zone and by the proteins involved. EB simplex (EBS) is characterized by separation occurring in the basal keratinocytes due to mutations in the keratin 5 and 14 genes or in the hemidesmosomal component plectin (Fuchs, 1992). In dystrophic EB (DEB), the skin separates at the lower layer of the basement membrane zone, the lamina densa, as a result of defects in anchoring fibrils (Uitto and Christiano, 1993). In junctional EB (JEB), blister formation takes place within the lamina lucida of the dermal-epidermal basement membrane and several mutations have been described in the three genes (LAMA3, LAMB3, and LAMC2) that encode the anchoring filament protein, laminin 5, and the two transmembrane components of the hemidesmosome (HD), collagen XVII and integrin.alpha.6.beta.4. Among the JEB variants, the nonHerlitz or mild forms of JEB (non-H JEB) are characterized by chronic and localized blistering with non-shortening of the patient's life span. Hemidesmosomes are present but usually reduced in number. Herlitz JEB (H-JEB) represents the most severe and the most frequent form of JEB (greater than 50% of cases). H-JEB is characterized by generalized blistering with erosions of the skin and mucous membranes, and is lethal in early childhood. Ultrastructural and immunohistochemical observations demonstrate abnormalities in hemidesmosome anchoring filaments complexes. Immunostaining of the skin of patients affected by H-JEB reveals absence of laminin-5. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with epidermolysis bullosa, 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 “epidermolysis bullosa” (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 epidermolysis bullosa. You can also use this procedure to view pending patent applications concerning epidermolysis bullosa. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON EPIDERMOLYSIS BULLOSA Overview This chapter provides bibliographic book references relating to epidermolysis bullosa. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on epidermolysis bullosa include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “epidermolysis bullosa” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on epidermolysis bullosa: •

Multi-Syndrome Guide to the Ectodermal Dysplasias Source: Mascoutah, IL: National Foundation for Ectodermal Dysplasias. 1999. 36 p. Contact: Available from National Foundation for Ectodermal Dysplasias. 410 East Main Street, P.O. Box 114, Mascoutah, IL 62258-0114. (618) 566-2020. Fax (618) 566-4718. Website: www.nfed.org. PRICE: Single copy free to families; additional copies and professionals $1.00. Summary: This booklet gives a brief overview of the several types of ectodermal dysplasias (ED) frequently found in the families of members of the National Foundation for Ectodermal Dysplasias (NFED). The authors discuss some aspects of development genetics, then describe ED and different types of ED syndromes. Some of the syndromes described may not be considered EDs in the strictest sense, but are included here because they are of interest to the NFED and because they complete the picture of how

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the EDs fit into the overall scope of birth defects and genetic disorders. The ED syndromes discussed are Christ Siemens Touraine syndrome, Clouston syndrome, Tooth and Nail syndrome, and Hair Tooth Nail syndrome. Complex ED syndromes covered are Ectrodactyly ED clefting syndrome, Hay Wells syndrome, Rapp Hodgkin syndrome, and Tricho Dento Osseous syndrome. Other syndromes with ED discussed are Goltz syndrome, Keratitis Ichthyosis Deafness syndrome, Trichorhinophalangeal syndrome, Cranioectodermal dysplasia, Ellis van Creveld syndrome, Oculodentodigital syndrome, Hallerman Streiff syndrome, Growth Retardation Alopecia and Pseudoanodontia Optic Atrophy. Other syndromes covered briefly are Incontinentia Pigmenti, Epidermolysis Bullosa, and Ichthyosis. The booklet concludes with a brief description of the mission of the NFED. The booklet is illustrated with black and white photographs of children and adults with various ED syndromes.

Chapters on Epidermolysis Bullosa In order to find chapters that specifically relate to epidermolysis bullosa, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and epidermolysis bullosa using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “epidermolysis bullosa” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on epidermolysis bullosa: •

Dental Aspects of Epidermolysis Bullosa Source: in Lin, A.N.; Carter, D.M. Epidermolysis Bullosa: Basic and Clinical Aspects. New York, NY: Springer-Verlag. 1992. p. 198-209. Contact: Available from Springer-Verlag New York, Inc. 175 Fifth Avenue, New York, NY 10010. (800) 777-4643; Fax (212) 533-3503. Summary: This chapter, from a medical text on the basic science and clinical aspects of epidermolysis bullosa (EB), covers the dental aspects of EB. Topics covered include the classification of EB; the anatomy and embryology of the tooth; intraoral pathology seen in EB simplex, junctional EB, and dystrophic EB; other intraoral manifestations, including dental caries and orthodontic problems; the social aspects; restorative procedures; prevention of dental problems; and covering EB in the student curriculum in dental schools. The authors provide management guidelines for the spectrum of intraoral problems faced by EB patients. 3 figures. 40 references.

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CHAPTER 6. PERIODICALS AND NEWS ON EPIDERMOLYSIS BULLOSA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover epidermolysis bullosa.

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

Gene therapy trial for epidermolysis bullosa underway Source: Reuters Industry Breifing Date: June 06, 2003

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Molecular basis of epidermolysis bullosa simplex described Source: Reuters Medical News Date: April 25, 2001 The NIH

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

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

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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for epidermolysis bullosa. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).

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

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

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

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to epidermolysis bullosa by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “epidermolysis bullosa” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for

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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for epidermolysis bullosa: •

Sucralfate suspension http://www.rarediseases.org/nord/search/nodd_full?code=187

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

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

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•

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

•

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

The NLM 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 “epidermolysis bullosa” (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 3200 14 12 1 74 3301

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 “epidermolysis bullosa” (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.

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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.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on epidermolysis bullosa 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 epidermolysis bullosa. 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 epidermolysis bullosa. 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 “epidermolysis bullosa”:

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Connective Tissue Disorders http://www.nlm.nih.gov/medlineplus/connectivetissuedisorders.html Dermatitis http://www.nlm.nih.gov/medlineplus/dermatitis.html Ehlers-Danlos Syndrome http://www.nlm.nih.gov/medlineplus/ehlersdanlossyndrome.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Head and Brain Malformations http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The 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 epidermolysis bullosa. 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.

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

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

•

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

•

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

•

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

•

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

•

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

•

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

Associations and Epidermolysis Bullosa The following is a list of associations that provide information on and resources relating to epidermolysis bullosa: •

Dystrophic Epidermolysis Bullosa Research Association of America,Inc. (DEBRA) Telephone: (212) 868-1573 Fax: (212) 868-9296 Email: [email protected] Web Site: http://www.debra.org Background: The Dystrophic Epidermolysis Bullosa Research Association of America (DEBRA) is a national voluntary health organization dedicated to achieving a cure for epidermolysis bullosa (EB) and improving the care and quality of life for people with this disorder and their families. EB is a group of genetic disorders in which there is a defect causing the skin layers to separate and blister either spontaneously or at the slightest friction. Symptoms usually are apparent at or shortly after birth. The Association promotes and supports scientific research on the cause, diagnosis, treatment, and cure of this disorder. DEBRA seeks to meet the unique needs of affected individuals and their families through programs that supply information, assistance, support, and guidance. DEBRA is also committed to raising public awareness about the nature of epidermolysis bullosa and to representing the special concerns of affected individuals and their families to government officials. The organization offers a variety of educational materials. Relevant area(s) of interest: Epidermolysis Bullosa

•

Dystrophic Epidermolysis Bullosa Research Association-United Kingdom Telephone: +44 1344 771961 Fax: 44 1344 762661 Email: [email protected] Web Site: http://www.debra.org.uk

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Background: The Dystrophic Epidermolysis Bullosa Research Association (DEBRA)United Kingdom is a nonprofit voluntary organization dedicated to offering information, assistance, and support to people whose lives are affected by Epidermolysis Bullosa (EB). EB is a group of genetic disorders in which there is a defect causing the skin layers to separate and blister either spontaneously or at the slightest friction. Symptoms usually are apparent at or shortly after birth. Established in 1978 by a group of parents with children affected by EB, DEBRA is committed to funding international research into the causes of and possible cures for EB; providing specialist nursing and paramedical staff to support families and professionals; and publishing an extensive range of informational materials for the medical community and the general public. DEBRA is also committed to providing specialist equipment or financial support in cases of special need; organizing, where appropriate, holidays for individuals with EB and their families; coordinating and assisting in the development of EB support groups worldwide; and encouraging the development of local treatment in the regions throughout the United Kingdom. DEBRA provides referrals including to genetic counseling, engages in patient advocacy and lobbying, offers networking services, and engages in patient and professional education. The organization offers a wide range of educational materials including fact sheets, brochures, pamphlets, booklets on all aspects of EB for professionals and affected families, bibliographies of medical journal articles published on EB, and videos. Relevant area(s) of interest: Acantholysis Bullosa, Acanthosis Bullosa, Bullosa Hereditaria, Epidermolysis Bullosa, Epidermolysis Hereditaria Tarda, Goldscheider's Disease, Heinrichsbauer Syndrome, Herlitz Syndrome, Keratolysis, Kobner's Disease

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to epidermolysis bullosa. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with epidermolysis bullosa. 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 epidermolysis bullosa. 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.

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To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “epidermolysis bullosa” (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 “epidermolysis bullosa”. 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 “epidermolysis bullosa” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “epidermolysis bullosa” (or a synonym) into the search box, and click “Submit Query.”

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

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

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

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

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

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

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

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

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

Basic Guidelines for Epidermolysis Bullosa Epidermolysis bullosa Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001457.htm

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Signs & Symptoms for Epidermolysis Bullosa Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Blister Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Blistering Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm Blisters Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003939.htm

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Contracture deformities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003185.htm Swallowing difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Swallowing difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm •

Diagnostics and Tests for Epidermolysis Bullosa Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Skin biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm

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Background Topics for Epidermolysis Bullosa Chafing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002034.htm Secondary infection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002300.htm

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

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

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

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

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

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EPIDERMOLYSIS BULLOSA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [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] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of

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antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha-helix: One of the secondary element of protein. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [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] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH]

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Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angioid Streaks: Small breaks in the elastin-filled tissue of the retina. [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] Anionic: Pertaining to or containing an anion. [EU] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms.

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[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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH]

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Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [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] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Balloon Dilatation: Nonoperative repair of occluded vessels, ducts, or valves by insertion of a balloon catheter. It is used, amoung other things, to treat varices, torn retinas, renal and biliary calculi, gastric, bronchial and rectal stenoses, and heart valves, and includes catheterization with Fogarty and Foley catheters. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [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]

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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-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up

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of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] 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] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [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] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH]

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Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell 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] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [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] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cicatricial: Ectropion due to scar tissue on the margins or the surrounding surfaces of the eyelids. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] 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

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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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices 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

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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [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] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] 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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Cutaneous: Having to do with the skin. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to

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anticancer drugs. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] 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] Dermo-epidermal: A patch of skin taken from the patient is directly grafted on the wound. [NIH]

Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and

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cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Desmosomes: Attachment bodies between cells such as in the corneal epithelium, which possibly allow tonofibrils to pass from cell to cell and which can degenerate to allow cells to migrate to cover a denuded area. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] 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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of

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abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [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] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum

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for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Stenosis: Stricture of the esophagus. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals,

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or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [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] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] 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

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diagnosis. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Conversion: The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue,

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organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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]

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Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

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] Glycoprotein: A protein that has sugar molecules attached to it. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Gynaecological: Pertaining to gynaecology. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hand Deformities: Alterations or deviations from normal shape or size which result in a disfigurement of the hand. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemidesmosomes: An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of desmosomes. They are composed of specialized areas of the plasma membrane where intermediate filaments bind on the cytoplasmic face to the transmembrane linkers, integrins, via intracellular attachment proteins, while the extracellular domain of the integrins binds to extracellular matrix proteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of

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glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] 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] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic

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acid can result in impaired hydroxyproline formation. [NIH] Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH] Ichthyosis Vulgaris: Most common form of ichthyosis characterized by prominent scaling especially on the exterior surfaces of the extremities. It is inherited as an autosomal dominant trait. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [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] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In 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] Induction: The act or process of inducing or causing to occur, especially the production of a

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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] 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]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] 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]

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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] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [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]

Invertebrates: Animals that have no spinal column. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Isozymes: The multiple forms of a single enzyme. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the

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blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as

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lotions for skin and vaginal lubricants. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH]

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Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]

Membrane: A very thin layer of tissue that covers a surface. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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] Microfibrils: Components of the extracellular matrix consisting primarily of fibrillin. They are essential for the integrity of elastic fibers. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [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] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [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 of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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

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from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multigene Family: The progeny of a single open-pollinated parent or of a single cross between two individuals. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be

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induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [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] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] 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] Nevus: A benign growth on the skin, such as a mole. A mole is a cluster of melanocytes and surrounding supportive tissue that usually appears as a tan, brown, or flesh-colored spot on the skin. The plural of nevus is nevi (NEE-vye). [NIH] 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

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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] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]

Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [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)

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from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Pediatric Endocrinologist: A doctor who sees and treats children with problems of the endocrine glands; diabetes is an endocrine disorder. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH]

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Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physicochemical: Pertaining to physics and chemistry. [EU] 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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pit and Fissure Sealants: Agents used to occlude dental enamel pits and fissures in the prevention of dental caries. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many

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bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH]

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Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Progeny: The offspring produced in any generation. [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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH]

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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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudoxanthoma: A rare disease of the skin characterized by the appearance of elevated yellowish papules or plaques, particularly on the neck, chest an abdomen and infrequently on the eyelids. [NIH] Pseudoxanthoma Elasticum: A rare, progressive inherited disorder resulting from extensive basophilic degeneration of elastic tissue, usually presenting after puberty and involving the skin, eye, and cardiovascular system. Characteristic manifestations are small, circumscribed yellowish patches at sites of considerable movement of the skin, angioid streaks in the retina, and a tendency towards hemorrhage and arterial insufficiency. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU]

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Pyloric Stenosis: Obstruction of the pyloric canal. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete

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remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal amyloidosis: A disease of unknown etiology characterized by the abnormal deposition of amyloid, a translucent homogenous glycoprotein, in various organs and tissues of the body. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] 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] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rod: A reception for vision, located in the retina. [NIH] Root Planing: A procedure for smoothing of the roughened root surface or cementum of a tooth after subgingival curettage or scaling, as part of periodontal therapy. [NIH] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]

Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [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] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast

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cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol

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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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells

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resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to

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cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less

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comparable to a leg. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombasthenia: A congenital bleeding disorder with prolonged bleeding time, absence of aggregation of platelets in response to most agents, especially ADP, and impaired or absent clot retraction. Platelet membranes are deficient in or have a defect in the glycoprotein IIbIIIa complex (platelet glycoprotein GPIIB-IIIA complex). [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [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] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH]

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Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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]

Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.

160

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[NIH]

Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] 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] Villus: Cell found in the lining of the small intestine. [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 kill, tumor cells. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [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]

Dictionary 161

Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] Xenograft: The cells of one species transplanted to another species. [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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

163

INDEX A Ablation, 14, 18, 67, 119 Abortion, 119, 138 Acantholysis, 108, 119, 147 Acceptor, 36, 119, 147, 159 Acetone, 10, 119, 141 Acne, 119, 140 Acne Vulgaris, 119, 140 Adaptation, 23, 119 Adjustment, 119 Adrenal Glands, 119, 121 Adverse Effect, 119, 140, 148, 154 Affinity, 20, 27, 119, 142, 155 Agar, 120, 148 Airway, 3, 72, 120 Algorithms, 120, 124 Alkaline, 23, 120, 125, 148 Alkaline Phosphatase, 23, 120 Allogeneic, 35, 71, 120 Allograft, 30, 72, 120 Alpha-helix, 120, 140 Alternative medicine, 90, 120 Aluminum, 76, 120, 156 Alveoli, 120, 129 Amino Acid Sequence, 23, 85, 120, 122, 133, 135, 150 Amino Acid Substitution, 7, 120 Amino-terminal, 120, 150 Amplification, 60, 120 Ampulla, 120, 132 Amyloid, 36, 121, 153 Amyloidosis, 44, 121 Anaemia, 54, 121 Anaesthesia, 36, 37, 121, 139 Analog, 4, 121 Analogous, 121, 159 Anaplasia, 121, 145 Anatomical, 121, 131, 138, 153 Anemia, 77, 117, 121, 144 Anesthesia, 5, 33, 120, 121 Anesthetics, 3, 121 Angiogenesis, 16, 17, 121 Angioid Streaks, 121, 151 Animal model, 11, 12, 16, 20, 21, 22, 25, 121 Anionic, 84, 121 Annealing, 121, 149 Anorectal, 56, 121

Antibacterial, 5, 121, 155 Antibiotic, 121, 147, 155 Antibodies, 12, 18, 20, 22, 40, 122, 123, 132, 136, 138, 142, 144, 148 Antibody, 120, 122, 124, 127, 132, 136, 137, 138, 139, 144, 155 Anticoagulant, 122, 151 Anticonvulsant, 122, 148 Antigen, 16, 20, 27, 33, 34, 49, 53, 70, 73, 119, 122, 127, 137, 138, 139 Antioxidant, 15, 122 Antiseptic, 119, 122 Anus, 121, 122, 123, 127, 140, 152 Aplasia, 37, 43, 122, 131 Apoptosis, 11, 122 Aqueous, 122, 129, 131, 141 Arterial, 22, 122, 151 Arteries, 22, 122, 124, 128, 136, 143 Arterioles, 122, 124, 125 Artery, 122, 124, 128, 151, 160 Ascorbic Acid, 122, 138 Assay, 7, 123 Atresia, 21, 30, 37, 42, 44, 46, 48, 51, 55, 56, 62, 64, 66, 123 Atrophy, 88, 119, 123 Attenuated, 13, 123, 159 Autoantibodies, 16, 20, 22, 34, 53, 70, 76, 123 Autoantigens, 80, 123 Autoimmune disease, 16, 20, 123 Autologous, 67, 71, 123 Autonomic, 123, 147 Axillary, 37, 123 Axons, 15, 123, 147 B Bacteria, 24, 121, 122, 123, 129, 132, 137, 143, 149, 155, 158, 159 Bacterial Physiology, 119, 123 Bacteriophage, 123, 139, 148, 158 Bacteriophage lambda, 123, 139 Balloon Dilatation, 45, 123 Basal cell carcinoma, 11, 18, 123 Basal cells, 13, 123 Base Sequence, 123, 134, 135 Basement Membrane, 13, 14, 15, 16, 17, 18, 21, 27, 31, 57, 58, 62, 63, 86, 123, 133, 141 Basophils, 124, 141 Benign, 16, 29, 32, 36, 46, 47, 124, 145

164

Epidermolysis Bullosa

Beta-pleated, 121, 124 Bilateral, 5, 32, 124 Bile, 124, 141, 156 Biliary, 123, 124, 125 Binding Sites, 22, 23, 24, 124 Biochemical, 22, 26, 29, 32, 124, 136, 141 Biopsy, 10, 13, 118, 124 Biosynthesis, 16, 124, 146, 159 Biotechnology, 16, 26, 28, 90, 101, 124 Bleeding Time, 124, 158 Blister, 4, 13, 14, 15, 25, 26, 79, 81, 86, 107, 108, 117, 124, 147 Blood Coagulation, 124, 125, 158 Blood pressure, 124, 144, 155 Blood vessel, 15, 17, 121, 124, 125, 126, 132, 135, 140, 143, 154, 155, 158, 160 Blot, 124, 138 Blotting, Western, 124, 138 Body Fluids, 124, 130, 146, 155 Bone Marrow, 124, 128, 132, 135, 136, 142, 144, 155, 156 Breeding, 13, 125 Bronchial, 123, 125 Buccal, 8, 125, 138, 142 C Calcification, 23, 125 Calcium, 7, 10, 125, 127, 143, 146 Calculi, 123, 125 Callus, 125, 131 Capillary, 17, 124, 125, 160 Carbohydrate, 16, 125, 136, 149 Carcinogenesis, 18, 125, 126 Carcinogenic, 125, 139, 146, 150 Carcinoma, 11, 49, 125 Cardiac, 125, 130, 145 Cardiomyopathy, 38, 44, 80, 125 Cardiovascular, 125, 151 Cardiovascular System, 125, 151 Case report, 5, 34, 35, 41, 45, 47, 50, 56, 61, 125 Catheter, 63, 123, 125, 140 Catheterization, 123, 126, 140 Cathode, 126, 131 Cations, 81, 126 Cell, 6, 8, 10, 11, 12, 13, 16, 17, 18, 20, 22, 24, 31, 36, 47, 58, 71, 119, 122, 123, 124, 126, 127, 129, 130, 131, 132, 133, 134, 135, 136, 139, 140, 141, 143, 144, 145, 148, 149, 150, 152, 153, 154, 156, 157, 158, 159, 160 Cell Adhesion, 126, 139 Cell Death, 122, 126, 145

Cell Division, 123, 126, 143, 148, 154 Chemopreventive, 15, 126 Chondrocytes, 23, 126, 133 Chromatin, 122, 126, 132, 145 Chromosomal, 120, 126, 144, 148 Chromosome, 21, 126, 141, 154 Chronic, 4, 13, 21, 47, 80, 85, 86, 119, 126, 127, 132, 139, 141, 147, 156, 157, 160 Chronic Disease, 126, 127 Chronic renal, 47, 126 Cicatricial, 12, 17, 33, 54, 126 Cleft Palate, 34, 126 Clinical trial, 6, 15, 18, 35, 101, 126, 128, 130, 151, 152 Clone, 20, 126 Cloning, 16, 21, 124, 126 Clot Retraction, 126, 158 Codon, 30, 48, 51, 58, 63, 126, 135 Cofactor, 127, 151, 158 Collagen disease, 23, 127 Colon, 36, 70, 127 Complement, 127, 135, 139 Complementary and alternative medicine, 79, 82, 127 Complementary medicine, 79, 127 Computational Biology, 101, 128 Conception, 119, 128, 133 Congenita, 37, 43, 128, 131 Congestion, 128, 132 Conjunctiva, 12, 128 Connective Tissue, 12, 84, 106, 122, 125, 127, 128, 129, 134, 136, 142, 143, 147, 153, 157 Connective Tissue Cells, 128 Connexins, 7, 128, 134 Contraindications, ii, 128 Cornea, 32, 128, 153, 156 Corneal Ulcer, 84, 128 Corneum, 128, 132, 138 Coronary, 128, 143 Coronary Thrombosis, 128, 143 Cranial, 128, 147 Crossing-over, 128, 152 Cultured cells, 8, 17, 128 Curative, 128, 157 Curettage, 128, 153 Cutaneous, 5, 8, 10, 14, 17, 18, 19, 20, 21, 27, 40, 51, 56, 77, 128, 140, 142, 148, 153 Cyclosporine, 76, 128 Cytokine, 7, 15, 43, 129 Cytoplasm, 122, 124, 129, 132, 145, 157 Cytosine, 85, 129

165

Cytoskeleton, 13, 39, 129, 139, 143 Cytotoxicity, 31, 129 D De novo, 21, 70, 129 Decubitus, 85, 129 Decubitus Ulcer, 85, 129 Deletion, 10, 19, 24, 36, 37, 52, 61, 122, 129 Denaturation, 129, 149 Dendritic, 129, 142 Density, 129, 149 Dental Care, 3, 5, 129 Dental Caries, 4, 5, 88, 129, 148 Dentition, 4, 5, 129 Dermal, 7, 14, 17, 21, 30, 35, 40, 44, 72, 79, 85, 129, 131 Dermatitis, 106, 129 Dermatosis, 17, 129 Dermis, 13, 129, 157 Dermo-epidermal, 80, 129 Desmin, 39, 129 Desmosomes, 130, 136 Developmental Biology, 16, 130 Diabetes Mellitus, 130, 135, 136 Diagnostic procedure, 83, 90, 130 Diarrhoea, 130, 138 Digestive tract, 130, 154, 155, 156 Dilation, 31, 38, 40, 130 Direct, iii, 18, 38, 130, 142, 150, 152, 157 Discrete, 7, 130 Dissection, 49, 130 Dissociation, 119, 130 Double-blind, 70, 130 Drug Interactions, 94, 130 Duct, 120, 126, 130, 156, 157 Duodenum, 124, 130, 131, 156 Dyes, 121, 124, 130, 145 Dysplasia, 5, 88, 130 Dystrophy, 16, 21, 39, 45, 52, 55, 59, 76, 130 E Ectoderm, 130 Ectodermal Dysplasia, 87, 130 Efficacy, 25, 40, 131 Elastic, 44, 131, 143, 151 Elastin, 121, 127, 131, 133 Elective, 15, 131 Electrolysis, 126, 131 Electrolyte, 131, 146, 155 Electrons, 122, 126, 131, 147, 152 Embryo, 16, 25, 119, 130, 131, 139, 146, 150 Embryogenesis, 7, 131 Embryology, 88, 131

Emulsion, 84, 131 Enamel, 4, 5, 129, 131, 140, 148 Endemic, 20, 131, 155 Endocrine Glands, 131, 147 Endogenous, 10, 13, 123, 131 Endoscope, 131 Endoscopic, 40, 131 Endothelial cell, 17, 132, 133, 158 End-stage renal, 126, 132 Environmental Health, 100, 102, 132 Enzymatic, 9, 120, 125, 127, 129, 132, 149 Enzyme, 84, 120, 132, 135, 139, 140, 149, 151, 156, 158, 159, 160, 161 Eosinophils, 132, 141 Epidermal, 7, 9, 10, 12, 16, 18, 21, 25, 40, 44, 67, 71, 77, 79, 86, 132, 140, 142 Epidermis, 10, 12, 13, 18, 21, 119, 123, 124, 128, 129, 131, 132, 138, 140, 147, 150, 151 Epidermoid carcinoma, 132, 155, 156 Epithelial, 6, 8, 11, 15, 19, 25, 57, 128, 132, 141 Epithelial Cells, 8, 25, 132, 141 Epithelium, 19, 123, 130, 132 Epitope, 20, 62, 70, 132 Epitope Mapping, 20, 132 Erythema, 30, 132 Erythrocytes, 121, 124, 132, 152 Erythropoietin, 77, 132 Esophageal, 31, 36, 38, 40, 45, 60, 63, 132 Esophageal Stenosis, 31, 36, 132 Esophageal Stricture, 38, 40, 45, 60, 63, 132 Esophagitis, 132, 156 Esophagus, 65, 123, 130, 132, 133, 152, 156, 160 Ether, 84, 133 Eukaryotic Cells, 10, 133, 146 Exogenous, 131, 133, 135 Exon, 19, 30, 47, 133 Extracellular, 7, 9, 11, 15, 16, 17, 24, 121, 128, 133, 136, 139, 143, 146, 155 Extracellular Matrix, 11, 16, 17, 128, 133, 136, 139, 143, 146 Extracellular Matrix Proteins, 133, 136 Extracellular Space, 133 Extraction, 9, 133 F Family Planning, 101, 133 Fat, 124, 129, 133, 141, 153, 155 Fetus, 38, 119, 132, 133, 150, 159 Fibril, 7, 14, 23, 133 Fibroblast Growth Factor, 32, 133

166

Epidermolysis Bullosa

Fibroblasts, 8, 12, 13, 14, 22, 27, 32, 54, 58, 62, 128, 133 Fibronectin, 27, 133 Fissure, 126, 133 Fluorescence, 33, 133 Foam Cells, 134, 161 Fold, 20, 133, 134 Frameshift, 19, 30, 43, 45, 134 Frameshift Mutation, 43, 134 Free Radicals, 122, 130, 134 Friction, 4, 107, 108, 134, 141 G Ganglia, 134, 145 Gap Junctions, 128, 134, 157 Gas, 134, 137, 144, 156 Gastric, 46, 123, 134, 147 Gastritis, 134, 156 Gastrointestinal, 30, 40, 63, 134, 156 Gastrostomy, 15, 46, 134 Gelatin, 134, 136 Gene Conversion, 10, 134 Gene Expression, 16, 23, 27, 36, 50, 53, 134, 135 Gene Library, 134, 135 Gene Targeting, 10, 135 Gene Therapy, 13, 18, 19, 21, 25, 31, 53, 65, 69, 71, 135 Genetic Code, 135, 146 Genetic Counseling, 21, 49, 108, 135 Genetic Engineering, 124, 126, 135 Genetic testing, 135, 149 Genetics, 12, 13, 21, 27, 29, 48, 51, 52, 59, 64, 66, 67, 72, 87, 135 Genital, 72, 135, 140 Genomic Library, 19, 135 Genotype, 15, 21, 42, 48, 135, 148 Gland, 16, 135, 142, 147, 148, 153, 154, 156, 157 Glomeruli, 135 Glomerulosclerosis, 37, 135 Glomerulus, 135 Glucose, 122, 130, 135, 136, 139 Glutamic Acid, 136, 145, 150 Glycine, 29, 47, 48, 49, 120, 136, 145 Glycoprotein, 132, 133, 136, 141, 142, 153, 158, 159 Glycosylation, 24, 136 Governing Board, 136, 150 Graft, 41, 136 Grafting, 58, 71, 136, 138 Graft-versus-host disease, 41, 136 Granulation Tissue, 17, 136

Gravis, 47, 55, 136 Groin, 49, 136 Growth Plate, 23, 136 Gynaecological, 65, 136 H Hair follicles, 129, 136, 160 Hand Deformities, 69, 136 Haptens, 119, 136 Heart Valves, 123, 136 Heme, 136, 149, 150, 159 Hemidesmosomes, 20, 49, 86, 136 Hemoglobin, 121, 132, 136, 137, 141, 150 Hemoglobinopathies, 135, 137 Hemorrhage, 137, 151 Hemostasis, 137, 139 Hepatic, 137, 149 Hereditary, 3, 43, 50, 59, 85, 130, 137 Heredity, 57, 119, 134, 135, 137 Herpetiformis, 38, 137 Heterodimer, 24, 137 Heterogeneity, 45, 51, 119, 137 Heterogenic, 137 Heterogenous, 5, 137 Holidays, 108, 137 Homeostasis, 9, 137 Homologous, 8, 13, 128, 135, 137, 154, 157 Hormone, 132, 137, 139, 153 Human growth hormone, 43, 137 Hybrid, 126, 137 Hydrogen, 119, 125, 129, 133, 137, 144, 146 Hydroxylysine, 127, 137 Hydroxyproline, 23, 120, 127, 137 Hyperkeratosis, 13, 43, 68, 138 Hypersensitivity, 138, 153 Hypertrophy, 138 Hypoplasia, 4, 131, 138 I Ichthyosis, 10, 88, 138 Ichthyosis Vulgaris, 10, 138 Immersion, 10, 138 Immune response, 122, 123, 136, 138, 156, 160 Immune system, 16, 138, 142, 148, 160 Immunoblotting, 41, 76, 80, 138 Immunochemistry, 132, 138 Immunofluorescence, 38, 53, 76, 138 Immunoglobulin, 35, 122, 138, 144 Immunohistochemistry, 28, 138 Immunology, 53, 119, 138 Impairment, 5, 138 Implantation, 16, 128, 138

167

In vitro, 10, 11, 14, 17, 23, 67, 79, 135, 138, 149, 158 In vivo, 10, 11, 12, 13, 17, 19, 22, 23, 26, 80, 135, 138 Incision, 138, 140 Induction, 18, 138 Infancy, 139 Infarction, 128, 139, 143 Infection, 12, 118, 123, 128, 139, 141, 142, 147, 153, 156, 160 Inflammation, 4, 16, 24, 85, 119, 129, 132, 134, 139, 140, 149, 153, 157, 160 Ingestion, 138, 139 Initiation, 8, 15, 18, 139 Insight, 19, 26, 139 Insulin, 67, 139, 140 Insulin-dependent diabetes mellitus, 139 Insulin-like, 67, 139 Integrase, 65, 139 Integrins, 21, 24, 136, 139 Intermediate Filaments, 25, 136, 139 Intestines, 123, 130, 134, 140, 154 Intracellular, 16, 54, 136, 139, 140 Intravenous, 54, 77, 140 Intrinsic, 120, 123, 140 Introns, 135, 140 Intubation, 3, 126, 140 Invasive, 18, 140 Invertebrates, 16, 140 Involution, 16, 140 Irritants, 7, 140 Ischemia, 123, 129, 140 Isotretinoin, 15, 35, 140 Isozymes, 11, 140 K Kb, 14, 100, 140 Keratin, 13, 25, 26, 29, 30, 31, 36, 39, 43, 46, 47, 49, 52, 57, 58, 60, 61, 67, 76, 86, 140 Keratinocytes, 8, 11, 13, 14, 16, 18, 19, 26, 27, 36, 37, 42, 46, 49, 50, 58, 59, 62, 71, 77, 80, 86, 140 Keratolytic, 129, 140 Ketoacidosis, 119, 140 Ketone Bodies, 119, 140 Kinetics, 58, 141 L Laminin, 11, 17, 18, 19, 24, 29, 53, 59, 63, 69, 80, 85, 123, 133, 141 Larynx, 56, 141, 158 Lectin, 77, 80, 141 Lens, 128, 141 Leprosy, 16, 141

Lethal, 22, 38, 51, 52, 61, 62, 86, 141, 144 Leucine, 52, 141 Leukemia, 135, 141 Leukocytes, 8, 124, 132, 141, 145, 159 Ligands, 24, 139, 141 Linkage, 8, 27, 48, 141 Lipid, 9, 134, 139, 141, 161 Liver, 121, 124, 131, 132, 137, 141, 149 Lobe, 137, 141 Localization, 138, 141 Localized, 4, 10, 33, 55, 60, 86, 121, 129, 130, 139, 141, 148, 159 Loop, 24, 31, 141 Lubricants, 141, 142 Lubrication, 4, 141 Lucida, 86, 141, 142 Lupus, 142, 157 Lymph, 123, 132, 142 Lymph node, 123, 142 Lymphatic, 139, 142, 143, 149, 155 Lymphocyte, 122, 142 Lymphoid, 122, 136, 142 Lysine, 137, 142, 150 M Macrophage, 12, 142 Macrophage Colony-Stimulating Factor, 12, 142 Malignancy, 65, 142 Malignant, 5, 142, 144, 145, 157 Malignant tumor, 142, 144 Mammary, 16, 142 Mammogram, 125, 142, 143 Maxillary, 5, 142 Mediate, 12, 142 MEDLINE, 101, 142 Melanocytes, 10, 142, 143, 145 Melanoma, 11, 142 Melanosomes, 142, 143 Mesenchymal, 15, 142, 143 Metastasis, 16, 143, 145 Metastatic, 16, 49, 77, 143, 153 Metastatic cancer, 16, 143 MI, 118, 143 Microbiology, 53, 119, 143 Microcalcifications, 125, 143 Microfibrils, 44, 143 Microfilaments, 139, 143 Microorganism, 127, 143, 160 Micro-organism, 129, 143 Microtubules, 139, 143 Migration, 15, 17, 18, 26, 47, 143 Milligram, 22, 143

168

Epidermolysis Bullosa

Mitochondrial Swelling, 143, 145 Mitosis, 122, 143 Mobility, 31, 143 Modeling, 6, 21, 143 Modification, 120, 135, 143, 152 Molecule, 7, 22, 122, 124, 127, 130, 132, 137, 141, 144, 147, 148, 149, 152, 158, 160 Monitor, 10, 144, 145 Monoclonal, 20, 138, 144 Monoclonal antibodies, 138, 144 Monocyte, 142, 144 Mononuclear, 142, 144, 159 Morphological, 131, 142, 144 Morphology, 7, 11, 22, 136, 144 Mosaicism, 63, 65, 144 Motility, 22, 144 Mucosa, 4, 5, 26, 142, 144, 156 Multigene Family, 25, 144 Multiple Myeloma, 41, 144 Muscle relaxant, 144, 148 Muscle Spindles, 144, 148 Muscular Dystrophies, 130, 144 Mustard Gas, 140, 144 Mutagenesis, 11, 144 Mutagens, 134, 145 Mutate, 11, 13, 145 Mydriatic, 130, 145 Myocardium, 143, 145 N Necrosis, 12, 122, 128, 139, 143, 145 Neonatal, 5, 26, 36, 145 Neonatal period, 5, 145 Neoplasia, 18, 145 Neoplasms, 40, 145 Nephropathy, 36, 145 Nerve, 16, 121, 123, 145, 150, 153, 155, 156, 159 Nerve Regeneration, 16, 145 Nervous System, 15, 134, 136, 145, 156 Networks, 13, 145 Neuronal, 145, 147 Neurotransmitter, 120, 136, 145, 156 Neutrophils, 141, 145 Nevus, 43, 145 Nuclear, 131, 133, 145 Nuclei, 131, 135, 140, 143, 145 Nucleic acid, 11, 85, 123, 129, 135, 145 Nucleus, 122, 124, 126, 129, 132, 133, 139, 144, 145, 146, 156 Nutritional Support, 134, 146 O Ocular, 12, 146

Oncogenic, 139, 146 Oral Health, 146 Oral Hygiene, 4, 5, 146 Oral Manifestations, 50, 146 Organ Culture, 146, 158 Organelles, 129, 142, 143, 146 Osmosis, 146 Osmotic, 58, 143, 146 Ossification, 146 Osteoblasts, 146 Osteocalcin, 23, 146 Osteogenesis, 23, 106, 146 Osteogenesis Imperfecta, 23, 106, 146 Oxidation, 119, 122, 146 P Palate, 34, 126, 147 Palliative, 72, 147, 157 Pancreas, 139, 147 Papillary, 138, 147 Partial remission, 147, 152 Particle, 11, 147, 158 Patch, 25, 129, 147 Pathogenesis, 16, 20, 147 Pathologic, 122, 124, 128, 138, 147, 150 Pathologic Processes, 122, 147 Pathologies, 24, 147 Patient Advocacy, 108, 147 Pediatric Endocrinologist, 6, 147 Pelvis, 147, 159 Pemphigus, 20, 119, 147 Penicillamine, 41, 147 Penicillin, 147, 159 Peptic, 147, 156 Peptide, 23, 84, 120, 133, 140, 147, 149, 150, 151 Peripheral blood, 8, 20, 147 Peripheral Nerves, 15, 141, 147, 155 Peripheral stem cells, 136, 147 Petrolatum, 131, 148 Phagocyte, 142, 148 Pharmacologic, 121, 148, 158 Phenolphthalein, 131, 148 Phenotype, 9, 14, 15, 19, 21, 25, 26, 27, 37, 42, 48, 61, 65, 67, 148 Phenytoin, 66, 148 Phosphorus, 125, 148 Photosensitivity, 148, 149 Physicochemical, 24, 138, 148 Physiologic, 124, 148, 152 Pigment, 142, 148 Pigmentation, 27, 61, 70, 148 Pit and Fissure Sealants, 5, 148

169

Pituitary Gland, 133, 148 Plants, 125, 135, 141, 144, 148, 158 Plaque, 4, 148 Plasma, 122, 133, 134, 136, 137, 144, 148, 152 Plasma cells, 122, 136, 144, 148 Plasmid, 14, 148, 160 Platelets, 149, 158 Platinum, 141, 149 Pleated, 140, 149 Plexus, 33, 149 Pneumonia, 128, 149 Point Mutation, 11, 13, 26, 36, 57, 58, 59, 149 Polyethylene, 85, 149 Polymerase, 60, 149 Polymerase Chain Reaction, 60, 149 Polypeptide, 120, 127, 149, 150, 151, 161 Polysaccharide, 122, 149, 151 Porphyria, 71, 149 Porphyria Cutanea Tarda, 71, 149 Porphyria, Hepatic, 149 Porphyrins, 149, 150 Postnatal, 150, 156 Postoperative, 3, 5, 150 Postoperative Complications, 3, 150 Postsynaptic, 150, 157 Potentiate, 18, 150 Practice Guidelines, 102, 150 Precancerous, 126, 150 Precursor, 132, 150, 159 Prenatal, 21, 38, 51, 66, 72, 131, 150 Prenatal Diagnosis, 38, 51, 66, 72, 150 Presynaptic, 145, 150, 157 Prevalence, 20, 150 Prickle, 119, 140, 150 Procollagen, 7, 150 Progeny, 144, 150 Progression, 11, 12, 18, 121, 150 Progressive, 126, 128, 140, 144, 145, 150, 151, 159 Proline, 52, 127, 137, 150 Promoter, 14, 19, 150 Prophylaxis, 4, 5, 150 Protease, 22, 151 Protein C, 84, 120, 123, 126, 135, 140, 146, 151 Protein Conformation, 120, 140, 151 Protein S, 16, 21, 124, 135, 137, 146, 151 Proteinuria, 135, 144, 151 Proteoglycans, 123, 133, 151 Protocol, 5, 151

Pruritic, 151, 153 Pruritus, 60, 151 Pseudoxanthoma, 66, 151 Pseudoxanthoma Elasticum, 66, 151 Puberty, 151 Public Policy, 101, 151 Publishing, 26, 42, 108, 151 Pulmonary, 40, 124, 136, 151, 160 Pulse, 144, 151 Pupil, 128, 130, 145, 151 Pustular, 119, 137, 151 Pyloric Stenosis, 39, 57, 152 Q Quality of Life, 85, 107, 152 R Race, 143, 152 Radiation, 133, 134, 152 Radioactive, 137, 138, 144, 145, 146, 152 Randomized, 70, 131, 152 Randomized clinical trial, 70, 152 Receptor, 10, 119, 122, 142, 152 Recombinant, 14, 16, 20, 22, 41, 134, 152, 160 Recombinant Proteins, 14, 20, 41, 152 Recombination, 8, 13, 135, 152 Reconstitution, 7, 152 Rectal, 123, 152 Rectum, 121, 122, 127, 130, 134, 152 Recurrence, 21, 152 Red blood cells, 132, 149, 152 Refer, 1, 125, 127, 141, 152 Reflux, 152, 156 Refraction, 152, 155 Regeneration, 6, 133, 152 Regimen, 80, 131, 152 Remission, 65, 152 Renal amyloidosis, 40, 67, 153 Respiration, 144, 153 Retina, 121, 141, 151, 153 Retinoid, 15, 153 Retrograde, 140, 153 Retroviral vector, 48, 135, 153 Rheumatism, 153 Rheumatoid, 84, 127, 153 Rheumatoid arthritis, 84, 127, 153 Rod, 16, 153 Root Planing, 5, 153 S Scabies, 37, 153 Sclera, 128, 153 Sclerae, 146, 153 Scleroproteins, 140, 153

170

Epidermolysis Bullosa

Sclerosis, 127, 153 Screening, 55, 126, 153 Sebaceous, 129, 140, 153, 160 Sebaceous gland, 129, 140, 153, 160 Secondary tumor, 143, 153 Secretion, 10, 24, 63, 119, 139, 154 Secretory, 53, 154, 157 Segmental, 37, 135, 154 Segmentation, 154 Segregation, 134, 152, 154 Seizures, 148, 154 Sensibility, 121, 154 Sequence Homology, 24, 154 Sequencing, 149, 154 Serous, 154 Serum, 127, 146, 152, 154, 159 Shock, 58, 154, 159 Side effect, 4, 93, 95, 119, 154, 158 Signs and Symptoms, 152, 154 Skeletal, 23, 129, 144, 154 Skeleton, 154 Small intestine, 130, 137, 140, 154, 160 Smooth muscle, 23, 128, 134, 154, 156 Social Environment, 152, 154 Sodium, 84, 154, 157 Soft tissue, 3, 124, 154, 155 Solid tumor, 121, 155 Solvent, 119, 146, 155 Somatic, 131, 143, 155, 157 Specialist, 108, 130, 155 Species, 120, 123, 130, 137, 143, 144, 152, 154, 155, 159, 160, 161 Specificity, 20, 24, 120, 155 Spectrum, 88, 155 Sperm, 126, 155 Sphincter, 141, 155 Spinal cord, 145, 147, 155 Spinal Nerves, 147, 155 Spinous, 132, 140, 155 Spleen, 121, 142, 155 Sporadic, 149, 155 Squamous, 11, 15, 18, 32, 35, 40, 45, 46, 49, 67, 68, 69, 77, 132, 155, 156 Squamous cell carcinoma, 11, 15, 18, 32, 35, 40, 45, 46, 67, 68, 69, 77, 132, 155 Squamous cells, 155, 156 Stabilization, 23, 148, 156 Statistically significant, 6, 156 Stem Cells, 25, 132, 147, 156 Stenosis, 77, 156 Stimulus, 156, 158

Stomach, 130, 132, 133, 134, 137, 140, 152, 154, 155, 156 Stool, 127, 156 Strand, 149, 156 Stress, 5, 58, 153, 156 Stricture, 132, 156 Stroma, 11, 156 Stromal, 18, 156 Subacute, 139, 156 Subclinical, 139, 154, 156 Subcutaneous, 18, 72, 156 Substance P, 152, 154, 156 Substrate, 136, 156 Sucralfate, 4, 69, 95, 156 Suction, 4, 156 Supplementation, 15, 156 Support group, 108, 156 Suppression, 25, 157 Sweat, 129, 157 Sweat Glands, 129, 157 Symptomatic, 25, 157 Synapses, 15, 157 Synaptic, 145, 157 Synaptic Vesicles, 157 Synergistic, 11, 157 Systemic, 12, 15, 34, 35, 44, 121, 124, 127, 138, 139, 156, 157 Systemic disease, 138, 157 Systemic lupus erythematosus, 34, 44, 127, 157 Systemic therapy, 12, 157 T Tear Gases, 140, 157 Telomerase, 42, 157 Teratogenic, 140, 157 Therapeutics, 10, 18, 94, 157 Thermal, 130, 149, 157 Thigh, 45, 136, 157 Threshold, 25, 158 Thrombasthenia, 24, 158 Thrombin, 151, 158 Thrombomodulin, 151, 158 Thrombosis, 24, 139, 151, 158 Tissue Culture, 8, 158 Tone, 146, 158 Tooth Preparation, 119, 158 Topical, 5, 11, 15, 25, 140, 148, 158 Toxic, iv, 12, 129, 130, 158 Toxicity, 130, 156, 158 Toxicology, 102, 158 Toxins, 122, 139, 144, 158 Trachea, 141, 158

171

Tracheostomy, 59, 158 Transcriptase, 157, 158 Transduction, 17, 158 Transfection, 59, 124, 135, 159 Transferases, 136, 159 Transgenes, 14, 159 Translation, 120, 159 Translational, 21, 159 Transmitter, 157, 159 Transplantation, 126, 159 Trauma, 4, 85, 133, 145, 159 Tryptophan, 127, 159 Tumor Necrosis Factor, 31, 159 Tumour, 159, 161 Tunica, 144, 159 U Ulcer, 129, 136, 156, 159 Ulceration, 129, 159 Unconscious, 121, 159 Uroporphyrinogen Decarboxylase, 149, 159 Uterus, 16, 119, 159 V Vaccines, 159, 160 Vaginal, 72, 142, 159 Valine, 147, 159 Valves, 123, 160 Varices, 123, 160 Vascular, 23, 24, 44, 129, 136, 139, 160 Vasculitis, 59, 160 Vector, 14, 16, 19, 158, 160

Vein, 140, 145, 160 Venous, 151, 160 Ventricle, 151, 160 Ventricular, 68, 160 Ventricular Dysfunction, 68, 160 Venules, 124, 125, 160 Vesicular, 137, 160 Veterinary Medicine, 101, 160 Villus, 44, 160 Viral, 10, 14, 19, 21, 128, 146, 158, 160 Viral vector, 14, 160 Virulence, 123, 158, 160 Virus, 10, 16, 123, 135, 148, 153, 158, 160 Vitamin A, 33, 153, 160 Vitro, 10, 11, 14, 17, 23, 160 Vivo, 10, 11, 13, 18, 19, 22, 23, 26, 71, 160 Vulgaris, 20, 119, 160 W White blood cell, 122, 141, 142, 144, 148, 160 Womb, 159, 161 Wound Healing, 4, 16, 17, 23, 54, 67, 133, 139, 161 X Xanthoma, 73, 161 Xenograft, 121, 161 Y Yeasts, 148, 161 Z Zygote, 128, 144, 161 Zymogen, 151, 161

172

Epidermolysis Bullosa