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

OSTEOPETROSIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES ...

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OSTEOPETROSIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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 Ó2003 by ICON Group International, Inc. Copyright Ó2003 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., 1960Osteopetrosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83719-8 1. Osteopetrosis-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 osteopetrosis. 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 OSTEOPETROSIS......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Osteopetrosis................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 25 The National Library of Medicine: PubMed ................................................................................ 26 CHAPTER 2. NUTRITION AND OSTEOPETROSIS ............................................................................... 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Osteopetrosis................................................................................ 91 Federal Resources on Nutrition ................................................................................................... 94 Additional Web Resources ........................................................................................................... 95 CHAPTER 3. ALTERNATIVE MEDICINE AND OSTEOPETROSIS ........................................................ 97 Overview...................................................................................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 97 Additional Web Resources ........................................................................................................... 99 General References ....................................................................................................................... 99 CHAPTER 4. CLINICAL TRIALS AND OSTEOPETROSIS ................................................................... 101 Overview.................................................................................................................................... 101 Recent Trials on Osteopetrosis................................................................................................... 101 Keeping Current on Clinical Trials ........................................................................................... 102 CHAPTER 5. PATENTS ON OSTEOPETROSIS ................................................................................... 105 Overview.................................................................................................................................... 105 Patent Applications on Osteopetrosis ........................................................................................ 105 Keeping Current ........................................................................................................................ 106 CHAPTER 6. BOOKS ON OSTEOPETROSIS ....................................................................................... 109 Overview.................................................................................................................................... 109 Book Summaries: Federal Agencies............................................................................................ 109 The National Library of Medicine Book Index ........................................................................... 110 Chapters on Osteopetrosis.......................................................................................................... 110 CHAPTER 7. PERIODICALS AND NEWS ON OSTEOPETROSIS ......................................................... 113 Overview.................................................................................................................................... 113 News Services and Press Releases.............................................................................................. 113 Academic Periodicals covering Osteopetrosis ............................................................................ 115 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 119 Overview.................................................................................................................................... 119 NIH Guidelines.......................................................................................................................... 119 NIH Databases........................................................................................................................... 121 Other Commercial Databases..................................................................................................... 123 The Genome Project and Osteopetrosis...................................................................................... 123 APPENDIX B. PATIENT RESOURCES ............................................................................................... 129 Overview.................................................................................................................................... 129 Patient Guideline Sources.......................................................................................................... 129 Associations and Osteopetrosis.................................................................................................. 132 Finding Associations.................................................................................................................. 132 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 135 Overview.................................................................................................................................... 135 Preparation................................................................................................................................. 135 Finding a Local Medical Library................................................................................................ 135 Medical Libraries in the U.S. and Canada ................................................................................. 135

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ONLINE GLOSSARIES ................................................................................................................ 141 Online Dictionary Directories ................................................................................................... 141 OSTEOPETROSIS DICTIONARY ............................................................................................. 143 INDEX .............................................................................................................................................. 195

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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 osteopetrosis 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 osteopetrosis, 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 osteopetrosis, 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 osteopetrosis. 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 osteopetrosis, 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 osteopetrosis. 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 OSTEOPETROSIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on osteopetrosis.

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

Osteopetrosis Source: American Family Physician. 57(6): 1293-1296. March 15, 1998. Contact: American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237 or (913) 906-6000. E-mail: [email protected]. Website: www.aafp.org. Summary: This journal article provides health professionals with information on the pathophysiology, clinical presentation, and clinical management of osteopetrosis. This rare hereditary bone disorder presents as osteopetrosis tarda, osteopetrosis congenita, or marble bone disease. Osteopetrosis tarda, the benign form, appears in adulthood, while the two more malignant variants, osteopetrosis congenita and marble bone disease, appear in infancy and childhood, respectively. In all three forms, the main features are

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pathologic alteration of osteoclastic bone resorption and thickening of cortical and lamellar bones. Osteopetrosis tarda is usually discovered accidentally on routine radiographs and is often asymptomatic; however, patients may also present because of related degenerative joint disease. Osteopetrosis congenita is associated with failure to thrive and growth retardation, results in bone marrow failure, and is almost always fatal. Marble bone disease causes short stature, cerebral calcification, and mental retardation. Osteopetrosis tarda requires no treatment, except in patients who present with surgical or medical complications. Bone marrow transplantation is the only chance for survival in patients with osteopetrosis congenita. 1 figure, 1 table, and 13 references. (AA-M).

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

Project Title: BIOCHEMICAL DEFICIENCIES

GENETICS

OF

CARBONIC

ANHYDRASE

Principal Investigator & Institution: Sly, William S. Chairman and Professor; Biochem and Molecular Biology; St. Louis University St. Louis, MO 63110 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 30-NOV-2003 Summary: The twelve known carbonic anhydrases (CAs) and CA-related proteins (CARPs) play important roles in diverse physiological processes including respiration, bone resorption, renal acidification, gluconeogenesis, signal transduction, and formation of cerebrospinal fluid and gastric acid. The recently discovered CA IX and CA XII are related to oncogenesis and are over-expressed in certain cancers. The broad goal of this research is to study the functional genomics of this gene family to determine the importance of individual members to health and disease. We have five specific aims: 1. Complete studies characterizing the biochemical and molecular genetics of CA II deficiency. CA II deficiency is the basis for the human inborn error of metabolism producing osteopetrosis, renal tubular acidosis, and brain calcification, novel studies are also proposed on the CA II-deficient mouse. 2. Characterize the mouse doubly deficient for CA II and CA IV and determine what other CA in kidney compensates for 2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

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CA IV deficiency. CA IV is the GPI-anchored membrane CA on surfaces of epithelial cells in kidney and gut and of capillary endothelial cells. The CA IV null mouse lacks the expected renal defect. 3. Characterize the CA VA gene knockout mouse, the newly discovered CA Vb, and candidates for CA V deficiency. CA VA is the mitochondrial CA thought to be involved in gluconeogenesis and ureagenesis. 4. Characterize CA IX and define its role in the regulation of cell proliferation and in oncogenesis. CA IX is a tumor-associated CA that is over-expressed in several cancers and expressed in normal stomach. 5. Characterize the properties and the functional genomics of CA XII. CA XII is a newly discovered, transmembrane CA that is over-expressed in several cancers and expressed in normal kidney and intestine. These studies should enhance our understanding of how thee individual carbonic anyhydrases contribute to normal physiology, how single CA deficiencies produce disease, and why the newly discovered CAs IX and XII are over-expressed in certain cancers, and should also suggest new targets for isozyme-specific CA inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BONE MATRIX AND BONE RESORPTION Principal Investigator & Institution: Odgren, Paul R. Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2002; Project Start 01-MAR-1986; Project End 30-APR-2007 Summary: (provided by applicant): These studies, all derived from our previous work exploring the interactions of bone matrix and bone resorption, focus on genes and other factors impacting skeletal development and resorption. Specific Aim 1 proposes mapping two unique mutations responsible for the failure of osteoclast development and function in the rat. This aim will be pursued using classical genetics combined with molecular mapping and positional cloning techniques to identify the genes responsible for the osteopetrotic phenotypes of the incisor absent (ia) and toothless (tl) rat mutations. These inbred strains that we have maintained for many years will be outcrossed with a highly polymorphic strain. A series of PCR reactions, linkage studies, and ultimately detailed sequence analyses will be used to identify the mutated genes. Candidates from a newly identified region in the tl rat are currently being evaluated. Specific Aim 2 explores the functional relationship between connective tissue growth factor (CTGF) secretion by osteoblasts and osteoclast recruitment and activation. We have shown up-regulation of CTGF mRNA and protein in vivo by osteoblasts in three osteopetrotic mutations in the rat and one in the mouse, all of which intercept osteoclast differentiation and/or function at distinct points. The commonality of CTGF overexpression implies that bone resorption is required to reduce CTGF to normal levels. We will test this hypothesis: (1) by curing mutant animals and following the impact on CTGF levels in vivo; (2) using osteoclast and bone organ culture systems, CTGF/osteoclast binding will be prevented by anti-CTGF antibodies and by saturating osteoclast alpha(v)beta(3) integrins with recombinant CTGF, and the effect on resorption will measured; (3) supernatants from resorbing cultures will be tested for their ability to down-regulate CTGF expression by osteoblasts. Specific Aim 3 will establish whether collagen gene switching dis-regulation is a common feature of growth abnormalities at craniofacial synchondroses and sutures. We have shown failures of collagen gene switching (types I and Ill and types II and X) at two key growth centers in the tl rat. We will extend these studies to the synchondroses of the skull base, and use this approach to screen a series of mice with craniofacial and/or osteopetrotic mutations for similar failures. This will establish how frequently collagen expression abnormalities accompany craniofacial defects, whether it constitutes a potential "read-out" for

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craniofacial growth defects, and therefore whether mechanistic future investigations are warranted. Hypothesis/Specific Aim 4. Extending studies of abnormal gene expression in osteopetrotic mutations will uncover more genes involved in regulating normal skeletal metabolism. We have previously used differential display of mRNA to discover several important skeletal genes. We will extend these studies using high-density gene array technology to compare normal, osteopetrotic, and cured osteopetrotic bone RNA to identify more genes and pathways that are up- or down-regulated in osteopetrotic mutations and that underlie osteoclast differentiation in vivo. This method will also permit us to follow the persistence of abnormal expression or its return to normal following restoration of resorption by cytokine treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: BONE MATRIX AND BONE RESORPTION Principal Investigator & Institution: Marks, Sandy C. Professor; Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 01-MAR-1986; Project End 14-JUL-2002 Summary: The regulation of osteoclastic bone resorption is a precise, complex process involving a number of mediators and cell types. Osteoblasts are among the major cells responsible for both recruitment and activation of osteoclasts. They act in a variety of ways to effect osteoclast development. This proposal uses 3 different osteopetrotic mutation in the rat, with known reductions in bone resorption and aberrations in osteoblast gene expression, bone matrix components and bone cell proliferation, to explore the regulation of bone resorption by osteoblasts and bone matrix constituents. Our specific aims are to determine the relationships of the osteoblast and osteoclast abnormalities in these 3 mutations, to characterize and quantitate protein synthesis and its regulation in mutant osteoblasts, to determine the ability of mutant osteoblasts and matrix products to recruit and direct differentiation and function of normal osteoclasts and to evaluate the role of the cytokine M-CSF in osteoblast and osteoclast function. To this end we will use cure of the disease in mutants and induction of the disease in normal littermates as mechanisms to perturb and follow osteoblast and osteoclast function by molecular techniques; mRNA levels of osteoblast-specific genes, +/- cDNA library screening and subtractive hybridization to detect unique genes of the osteopetrotic phenotype, and PCR amplification to dissect aberrant genes by nucleotide analyses. Osteoblast gene expression and its hormonal regulation will be compared in cultures of mutant and normal osteoblasts and metatarsal cultures and bone slices will be used to analyze the ability of mutant bone matrix and osteoblasts to direct osteoclast differentiation and function, respectively. Finally, the ability of M-CSF gene expression in this mutation, and to study the role of this cytokine in skeletal development by in situ hybridization. Future studies will be directed toward gene therapy for this mutation. These studies are expected to provide insights into the cellular and molecular bases for the regulation of bone resorption and have application in situations where selective regional or general reductions or accelerations of bone resorption are desirable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: BONE RESPONSE TO COMBINED MECHANICAL AND PTH STIMULATION Principal Investigator & Institution: Guo, X. Edward. Associate Professor; Mechanical Engineering; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027

Studies

7

Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant): Trabecular bone adaptation plays a significant role in the etiology of many metabolic bone diseases such as osteoporosis and osteopetrosis, bone loss in microgravity, and the long term success or failure of porous implants in total joint arthroplasty. Parathyroid hormone (PTH) is an important anabolic agent when administered intermittently. We have developed a novel in vivo rat-tail vertebra model coupled with an uCT image based finite element technique. Specifically, a controlled mechanical load can be applied to a rat-tail vertebra and a detailed threedimensional (3D) stress/strain environment in the trabecular bone tissue can be determined using an advanced finite element microstructural model. In this proposal, we designed a full-scale, long-term study to systematically quantify the molecular/cellular responses and changes in 3D morphology in trabecular bone to combinations of mechanical loading and PTH treatment. The molecular responses will be assayed using RT-PCR and in situ hybridization. The bone cellular response will be quantified using bone histomorphometric techniques. The specific aims of this project are: Specific Aim 1: To determine the changes in gene expression (c-fos, cbfa-1, IGF-1, collagen a1(I), osteopontin, osteocalcin, alkaline phosphatase, RANK-L, and osteoprotegerin) by RT-PCR and in situ hybridization, bone cell activities by bone histomorphometry, and 3D trabecular bone morphology by uCT of rat tail vertebrae at various levels of mechanical loading (ON, 50N and lOON) ranging from 1 day to twelve weeks. Specific Aim 2: To determine the changes (using the same measurements cited in Specific Aim 1) in rat-tail vertebrae in response to daily PTH administration (3O-ug/kg and 6Oug/kg) for various lengths of time. Specific Aim 3: To determine the changes (using the same measurements cited in Specific Aim 1) in rat tail vertebrae mechanically loaded at various magnitudes (ON, SON, and lOON) in the presence of PTH (30ug/kg and 6O ug/kg) for various lengths of time. Specific Aim 4: To perform uCT based PEA of the loaded vertebrae in Specific Aims 1 and 3, and to determine the changes in the distribution of trabecular bone tissue stress/strain parameters following the various treatments. Results from this study will help to clarify, in a quantitative manner, the cellular and molecular mechanisms of bone adaptation to mechanical loading, which are important in the understanding of the etiology and optimizing therapeutic interventions of menopausal, microgravity or age related osteoporosis, and improvement in total joint replacements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CSF1 GENE EXPRESSION IN OSTEOCLAST BIOLOGY Principal Investigator & Institution: Abboud, Sherry L. Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-DEC-2002 Summary: CSF-1, released by osteoblasts and stromal cells, stimulates the proliferation and differentiation of osteoclast progenitors and enhances osteoclast survival. In the op/op mouse model, a thymidine insertion in the coding osteopetrosis.. The long-term goal of this proposal is to determine the effect of soluble(s) and membrane-bound (m) CSF-1 isoforms on osteoclastogenesis and define cell-specific cis-acting elements in the 5' flanking region of the CSF-1 promoter that regulate their expression. Our first hypothesis is that sCSF-1 and mCSF-1 are differentially synthesized and stimulate osteoclast formation due, in part, to their interaction with the c-fms receptor. To address this issue in vitro, op/op stromal cells will be transfected with sCSF-1 or mCSF-1 cDNA and stable transfectants examined for CSF-1 synthesis, bioactivity, osteoclast support and c-fms tyrosine kinase activation in target cells. The effect of each isoform on

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Osteopetrosis

osteoclast formation in vivo will be explored by targeting isoform to ameliorate osteopetrosis in op/op mice, genetic crosses between sCSF-1 and mCSF-1 transgenic mice and heterozygous op/wt mice, genetic crosses between sCSF-1 and mCSF-1 transgenic mice and heterozygous op/wt mice will be carried out to establish op/op mutants expressing each transgene. Mice will be examined for serum CSF-1 bone growth, incisor eruption and resolution of osteopetrosis.. Bone sections will be assessed for osteoclast activity; histomorphometric analysis will evaluate both static and dynamic indices of bone remodeling. The in vivo therapeutic effect of targeting each isoform to the bone in op/op mice will be assessed using adenoviral vectors designed to limit CSF1 expression in osteoblasts. Our second hypothesis is that specific regulatory elements in the 5' flanking region of the CSF-1 promoter direct cell-specific gene expression in vitro and in vivo during murine development. The temporal and spacial expression of CSF-1 during murine skeletal development will be assessed by in situ hybridization and immunohistochemistry. To determine potential cis-acting elements that control cellspecific expression of CSF-1, deletion constructs generated from the 5' flanking region of CSF- 1 will be tested for their ability to direct transcription in osteoblast, stromal, liver, muscle, epithelial and B cell lines. Relevant CSF-1 cell specific promoter sequences will be assessed in vivo by generating transgenic mice harboring cell-specific CSF-1 promoter segment(s) linked to the bacterial lacZ reporter gene. These studies should increase our understanding of the molecular mechanisms that activate CSF-1 during development and may suggest novel therapeutic strategies designed to regulate osteoclast formation in a variety of bone disorders such as osteoporosis and bone fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: CYTOSKELETAL REGULATION BY SRC64/TEC29 KINASES Principal Investigator & Institution: Simon, Michael A. Associate Professor; Biological Sciences; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Members of the SRC family of non-receptor protein tyrosine kinases (SFKs) play crucial roles in the regulation of cellular growth, differentiation, and morphology. Studies in vertebrates have shown that inappropriate activation of SFKs can lead to oncogenic transformation of cells, while the absence of SFKs has been associated with defects in signaling by the B and T cell antigen receptors and with defects in bone resorption (osteopetrosis). Among the important cellular consequences of altered SFK function are defects in the cellular actin cytoskeleton. The aim of the proposed research is to investigate how SFKs participate in cytoskeletal regulation. We are addressing this issue by studying the action of a particular SFK, the product of the Drosophila Src64 gene. We have chosen to study Src64 because of the ability to perform genetic studies that would be either difficult or impossible to conduct in vertebrate organisms. Our goal is to combine these genetic studies with extensive biochemical analysis in order to understand Src64 function. In our previous work, we identified mutations that inactivated the Src64 gene. We showed that the lack of Src64 function has a surprisingly specific phenotype: Src64 mutant animals are fully viable, but the females are partially sterile. Our analysis of this phenotype revealed that it is associated with defects in the morphogenesis of specialized actin cytoskeletal structures, called ring canals, that form at the cytoplasmic bridges connecting the developing oocyte and its adjacent cluster of nurse cells. We then genetically identified the Tec29 protein as a major target of SRC64 action. ThC29 is a member of a family of tyrosine kinases that includes vertebrate proteins such as Bruton's tyrosine kinase, whose absence in humans leads to X-linked

Studies

9

agammaglobulinemia. We showed that TEC29 is essential for normal ring canal morphogenesis and is recruited to the growing ring canals in response to SRC64 activity. The goals of the proposed research are to further characterize the role of SRC64 and TBC29 in actin cytoskeletal regulation by: 1) investigating the role of SRC64 and ThC29 using domain specific mutagenesis, 2) investigating the biochemical basis for SRC64 regulation of TEC29, 3) identifying and characterizing substrates of TEC29, 4) cloning and analyzing E(Src64)2B, another potential target of SRC64, and 5) conducting further genetic screens to identify additional components of the SRC64/TEC29 pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: DISCOVERY AND FUNCTIONAL ASSESSMENT OF THE RAT OP GENE Principal Investigator & Institution: Dobbins, David E.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, MD 20852 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Bone is an extremely dynamic tissue that undergoes remodeling throughout life. Control of bone homeostasis is achieved through a complex combination of influences involving numerous cytokines, growth factors, steroid hormones and various calcitrophic molecules. These multi-functional effector molecules unite to regulate osteoclastic bone resorption and osteoblastic bone formation. Any disequilibrium in the control of osteoclasts and osteoblasts can lead to a variety of bone diseases in which inappropriate bone homeostasis is manifest. Osteopetrosis is caused by a heterogeneous group of congenital bone diseases that are characterized by a generalized increase in skeletal mass resulting from inadequate osteoclastic bone resorption. To date, the precise genetic control of osteoclast function remains inadequately understood and improved treatment of bone disease awaits a further elucidation of the complex control mechanisms of bone homeostasis. The objective of the proposed research is to examine the genetic control of osteoclast function with the use of an animal model of flawed bone resorption, the op osteopetrotic rat. The specific aims of this project are to 1) sequence functional candidate genes within the 0.51 cM genetic critical region to identify the gene responsible for osteopetrosis in the op rat. 2) validate that the genetic mutation identified within the op critical region is indeed responsible for the osteopetrosis and to begin to characterize the mechanisms of action whereby osteoclast function is compromised. Data from this project may reveal novel mechanisms in the control pathways of bone homeostasis that are relevant to numerous human bone diseases. Identification of the molecular mechanisms of failed bone homeostasis may reveal additional molecular therapeutic targets that can be pursued to improve the clinical treatment of a myriad of human bone diseases such as osteopetrosis, osteoporosis and rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FIRST INTERNATIONAL SYMPOSIUM ON OSTEOPETROSIS: Principal Investigator & Institution: Orchard, Paul J. Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): "The First International Symposium on Osteopetrosis: Biology and Therapy" will take place at the Natcher Center, National Institutes of Health, on October 23-24, 2003. This meeting, which is jointly sponsored by the Paget Foundation, was organized to facilitate discussion of clinical and basic

10 Osteopetrosis

research applicable to the disorders described as osteopetrosis.. The intention is to bring together leaders in the field of bone biology, genetics and clinical care of these patients, recognizing that there has been significant recent gains in basic and clinical research relevant to this disorder. Objectives of this Symposium are outlined in Specific Aims. Approximately 45 persons will attend. Osteopetrosis is a heterogeneous group of inherited conditions characterized by a defect in bone resorption by osteoclasts, leading to an increase in skeletal mass and bone density. In the more severely affected individuals, the lack of osteoclast function leads to a bone marrow cavity insufficient to support hematopoiesis. Autosomal recessive osteopetrosis is fatal in the majority of patients before they reach 10 years of age, generally from marrow failure and bleeding or infections. The molecular basis of human osteopetrosis has remained elusive until very recently. It is now appreciated that several gene defects leading to an inability of osteoclasts to acidify the extracellular space are responsible for approximately 70% of occurrences of autosomal recessive osteopetrosis.. However, there is little information yet available regarding the correlation of genotype and phenotype in affected individuals. In addition, it is clear that there are genetic defects that have not yet been defined. Therapeutic approaches for osteopetrosis have been limited. Interferon-7 has been shown to increase the function of osteoclasts from patients with osteopetrosis, but this is not universal, nor is it necessarily maintained. Hematopoietic cell transplantation has been shown to be effective, but it is difficult, expensive and life-threatening complications are commonly observed. Based on the new information available regarding these disorders, the goal of "The First International Symposium on Osteopetrosis: Biology and Therapy," jointly sponsored by The Paget Foundation, is to facilitate discussion of clinical and basic research applicable to the disorders described as osteopetrosis by leaders in the field of bone biology, genetics, and clinical care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: G PROTEIN RECEPTOR--STRUCTURAL CHARACTERIZATION Principal Investigator & Institution: Mierke, Dale F. Associate Professor; Mol Pharm, Physiology/Biotech; Brown University Providence, RI 02912 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 30-JUN-2006 Summary: (provided by applicant): We aim to probe the structural features of the Gprotein coupled receptors (PTH1 and PTH2) for parathyroid hormone (PTH). PTH is one of the few bone-active agents proven to be anabolic in humans and therefore has been intensively examined as a possible target for the treatment of osteoporosis. We aim to characterize, on a structural basis, the association of the receptor to the G-proteins (Gs and Gq) known to couple to it. Additionally, the association of PTH1 to beta-arrestin2, an important step in the internalization of the receptor will also be structurally examined. A second aim is to utilize the structural features of PTH and PTH1 previously determined in our group to rationally design low molecular weight PTH-based analogs. It is well established that the N-terminus of PTH is responsible for receptor activation. However, this domain alone, PTH(1-14), has extremely low binding affinity. Through random screening, analogs with low uM potencies (e.g., (Ala3, 10,12, Arg11)PTH(1-14)) have been developed. Our structural characterization of this lead compound has provided a number of methods to incorporate additional conformational constraint (cyclization) as well as non-natural amino acids and peptidomimetics. The research described here will facilitate the rational design and optimization of PTH-based agents for the regulation of calcium homeostasis. A final aim is to utilize the establishment of the pharmacophore for the PTH1 receptor, as well as structural characterization of TIP39 (tuberoinfundibular peptide-39) to develop a structure-activity relationship for the

Studies 11

PTH2 receptor. Such information would facilitate the design of stable, PTH2 specific antagonist, which would assist in the establishing the physiological role of the receptor, thought to be involved in release of pituitary and pancreatic hormones and possibly perception of pain. Given that PTH activates both receptors, and TIP39(7-39) is specific for PTH1, there is a great synergy between the latter two aims; the results aimed to develop a valuable tool for the physiological characterization of PTH2 will accelerate the rational design of PTH1 receptor-specific, lead drug candidates for the treatment of osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENERAL CLINICAL RESEARCH CENTER Principal Investigator & Institution: Mccurdy, Layton; None; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-MAR-1977; Project End 01-MAR-2001 Summary: This renewal application is a request for continuing support of the General Clinical Research Center at the Medical University of South Carolina. The GCRC is composed of an eight-bed inpatient unit and an outpatient facility featuring eight examination rooms. Major areas of research include: the pathobiology and treatment of severe congenital osteopetrosis;; the genetic basis of insulin resistance in noninsulin dependent diabetics; the pathophysiology and treatment of hypertension; the role of hyperhomocyteinemia in vascular disease; the biochemical, hormonal and genetic characterization of the difference in bone and mineral metabolism in blacks compared to whites, the etiology of growth failure in sickle cell disease; the treatment of advanced mitral insufficiency with beta blockers; the effect of pentoxyphylline on renal function after cardiac transplantation; the etiology of panic disorder, the psychobiology of depression in children; the treatment of alcoholism; the treatment of Raynaud's Phenomenon; the role of thromboxane A2 in prostate hypertrophy, the molecular basis of prostatic cancer; the molecular basis of pancreatic cancer; the role of nutrition in breast cancer therapy; immunotoxin therapy of T cell ALL, the role of CEA virus vaccination in treating lung, breast, and gastrointestinal adenocarcinoma; dietary therapy of obesity; the stereospecific metabolism of beta blockers; neonatal adrenal function; and treatment of patients with HIV infections. The goal of the GCRC is to support existing clinical research, provide facilities and programs which stimulate the development of new areas of clinical research, facilitate the movement of basic science to clinical reality, and to train clinical investigators and support staff to ensure that patient oriented studies continue to be the ultimate level of medical research. Molecular biology, immunotherapy, cytokine therapies, and computer technology complement the traditional strengths of this GCRC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC AND CLINICAL STUDIES OF AD02 Principal Investigator & Institution: Econs, Michael J. Associate Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2002; Project Start 03-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Type 2 autosomal dominant osteopetrosis is an inherited disorder characterized by osteosclerosis, end-plate thickening of the vertebrae and endobones. Although the disorder results in high bone mineral density, the bone is of poor quality and patients frequently present with fracture. Other features of the

12 Osteopetrosis

disease include nerve entrapment syndromes and osteomyelitis. Although the disorder is secondary to defects in osteoclast mediated bone resorption the pathophysiology of this disease has not been elucidated. The goals of the proposed investigations are to characterize type 2 autosomal dominant osteopetrosis and to identify the gene(s) responsible for this disorder using positional cloning techniques. Identification of the ADO2 gene(s) will provide substantial insight into the pathogenesis of ADO2 and to the basic biology of osteoclast function and regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: GENETIC CONTROL OF VACUOLAR H+-ATPASE EXPRESSION Principal Investigator & Institution: Lee, Beth S. Assistant Professor; Physiology and Cell Biology; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 30-JUN-2006 Summary: (provided by applicant): The vacuolar proton-translocating ATPase, or VATPase, is a multi-subunit complex that uses energy from ATP hydrolysis to transport protons across cellular membranes. In most eukaryotes, V-ATPases reside solely in membranes of the endocytic network, where they serve to acidify endosomes, lysosomes, the trans-Golgi, and other vacuolar compartments. However, some specialized cell types, including kidney epithelia, osteoclasts, macrophages, and neurons, express the V-ATPase at high levels and in specialized subcellular compartments, where the enzyme is critical for such diverse functions as urinary acidification, bone resorption, regulation of intracellular pH, and regulated vesicular uptake of neurotransmitters. The variety of functions performed by V-ATPases among mammalian cells is attributable to expression of multiple subunit isoforms, differences in overall expression levels, and the capacity for regulated targeting to specialized membrane compartments. Inappropriate expression of V-ATPase in humans has been shown to lead to serious disease states, including renal tubular acidosis, deafness, and osteopetrosis.. The genetic controls that regulate V-ATPase expression must be varied and diverse to meet the specific proton-transport needs of many specialized cell types, as well as its constitutive role in the endocytic network. These include both transcriptional and post-transcriptonal mechansims, as well as intracellular targeting of both V-ATPase mRNA and proteins. The long-term goal of this project is to understand the mechanisms by which V-ATPases are expressed at appropriate levels and in appropriate membrane compartments. To this end, the specific aims are directed toward (1) examining mechanisms by which V-ATPase mRNA stability is regulated in protonsecreting cells such as macrophages and kidney epithelia; (2) examining determinants within V-ATPase mRNAs that mediate intracellular trafficking in specialized cell types; and (3) defining genetic elements that control expression of a uniquely regulated VATPase subunit involved in intracellular trafficking. These aims will be achieved through experiments in which V-ATPase mRNAs are genetically manipulated in cell culture models; the effects of these manipulations of V-ATPase expression and cell function will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERFERON GAMMA 1B IN TREATMENT OF OSTEOPETROSIS Principal Investigator & Institution: Key, Lyndon L.; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001

Studies 13

Summary: Prior study has provided data suggesting that interferon gamma 1b improves bone resorption, yielding an increse in bone marrow space; improves white cell superoxide production, and reduces the trend toward progressive narrowing of the cranial nerve foramina. This study proposes to determine if interferon gamma 1b therapy combined with calcitriol can improve bone turnover, marrow function, and the size of cranial nerve foramina in severe osteopetrosis to a greater extent than calcitriol alone through a randomized, controlled, open-label trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: INTERFERON GAMMA THERAPY OF OSTEOPETROSIS Principal Investigator & Institution: Willi, Steven M.; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001 Summary: The objective of this proposal is to determine if interferon gamma is a safe and effective therapy for severe, malignant osteopetrosis in children and adults. Treatment with recombinant human interferon gamma (rIFN) will be compared to the accepted therapy of bone marrow transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: JUVENILE OSTEOPETROSIS: DBP-MAF, A NEW THERAPEUTIC AGENT Principal Investigator & Institution: Swamy, Narasimha M. Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 21-MAY-2001; Project End 31-JAN-2002 Summary: Juvenile osteopetrosis is an inherited skeletal disorder resulting from reduced osteoclast-mediated bone resorption. Activation of osteoclasts is known to promote bone resorption and alleviate the disease and associated symptoms. Vitamin Dbinding protein-macrophage activating factor (DBP-MAF) is a newly discovered osteoclast activator, which has shown therapeutic potential in animal models. An impaired osteoclast activity (leading to osteopetrosis) has been recently shown to be due to a generalized defect in enzymatic conversion of DBP (vitamin D binding protein) to DBP-MAF by T- and B- lymphocytes in both humans and animal models. Infusions of ex vivo generated DBP-MAF has been shown to increase osteoclast mediated bone resorption in animal models. This warrants further research to evaluate the therapeutic potential of DBP-MAF human osteopetrosis.. A clear understanding of the underlying mechanism of osteoclast activation by DBP-MAF in humans is necessary to develop DBP-MAF as a therapeutic agent for osteopetrosis.. We propose to achieve this goal by (i) Systematic evaluation of DBP- MAF mediated activation of osteoclasts from normal and osteopetrotic subjects and (ii) Determining the functionality of DBP, osteoclasts and DBP-MAF from osteopetrotic children. The proposed research not only intends to gain an insight towards the cellular and/or molecular defects leading to an excessive accumulation of bone in osteopetrotic subjects, but also offers a unique opportunity of methodology development to determine the underlying defect in a given 'clinical case', which would lead to a better course of therapeutic options. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF CIC-TYPE CHLORIDE CHANNELS FUNCTION Principal Investigator & Institution: Melvin, James E. Interim Director; Eastman Dentistry; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant) Voltage-activated, CIC chloride (CI-) channels are essential for survival as illustrated by various inherited human diseases and knockout mouse models. Genetic mutations of distinct members of the CIC gene family lead to either impaired transepithelial ion transport in Bartter's syndrome, to increased muscle excitability in myotonia congenita, to reduced endosomal acidification and endocytosis in Dent's disease, or to impaired extracellular acidification by osteoclasts in osteopetrosis.. Moreover, targeted disruption of several CIC channel genes in mice results in blindness. The three-dimensional structure of bacterial CIC channels determined by X-ray analysis provides the structural framework needed to perform structure-function analysis of CIC channel proteins in order to understand their biophysical properties, including the mechanism by which these channels are activated. This project will determine the gating and modulation of the CIC-2 CI-channel cloned from mouse parotid acinar cells when expressed in human kidney cells. We will determine if fast and slow gating processes control the kinetics of CIC-2, as shown for CIC-0 and CIC-1. Next, we will investigate how the large changes in intracellular and extracellular [CI-] and [H+] that epithelial cells undergo affect gating. We hypothesize that these changes serve as feedback signals that regulate channel activity as follows: chloride ions, by serving as a charge provider, regulate the voltage sensitivity of gating; and protons regulate channel activity by interacting directly with the gating machinery of the CIC-2 channel. Thus, we propose that the identification of the H+ binding sites will define the structural determinants of CIC-2 gating. The experiments proposed in Aim 1 will study the gating of CIC-2 and identify amino acids that form the gates of the channel. Aims 2 and 3 are designed to define the effects of CI- and H+ on CIC-2 CIchannel gating, as well as the molecular domains conferring voltage and pH sensitivity with the ultimate goal of defining the structure(s) responsible for gating. A combination of electrophysiological, molecular biology and amino acid-labeling techniques will be used to perform structure-function analysis of the channel protein and to track changes in gating, CI- and H+ sensitivity. This research will be carried out primarily at Universidad Autonoma de San Luis Potosi, Mexico in collaboration with Dr. Jorge Arreola as an extension of NIH grant # R01 DE09692. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROPHTHALMIA IN OSTEOCLAST DEVELOPMENT Principal Investigator & Institution: Weilbaecher, Katherine M. Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: The microphthalmia (mi) gene is critical for osteoclast development based on severe osteoclast defects in mi/mi mutant mice. These mice represent a genetically defined animal model of osteopetrosis secondary to profound failure of osteoclast function, despite normal osteoclast numbers. Osteoclasts play an important role in the pathogenesis of osteoporosis, osteopetrosis, and a variety of pathological features of metastatic cancer, such as bony invasion, pathologic fractures, and bone pain caused by many human tumors. Thus, osteoclast function lies at the crossroads of many human diseases of particular relevance in bone development and aging. In addition, osteoclasts provide an attractive system to study the function of the transcription factor

Studies 15

microphthalmia (Mi). The mi gene encodes a basic/helix-loop-helix/leucine zipper (bHLH-ZIP) transcription factor related to the oncoprotein, Myc. The mi mutant phenotype in mice includes osteopetrosis, a lack of pigmentation, small eyes, and a mast cell defects. Our laboratory has biochemically characterized DNA binding, transcriptional activity, and identified three dimerization partners of Mi. In addition we have recently discovered that the Mi protein is phosphorylated in response to c-kit (stem cell factor receptor) activation via a signaling pathway involving MAP kinase and that this phosphorylation enhances Mi transcriptional activation. This observation was sparked by the similarity of pigment cell defects in mi/mi and kit mutant mice. Mice with mutations in M-CSF develop osteopetrosis.. M-CSF receptor is closely related to ckit, and in present preliminary evidence that when primary osteoclast-like cultures are stimulated with M-CSF, the Mi protein undergoes a posttranslational modification (likely phosphorylation). Given that both M-CSF and Mi are critical for osteoclasts, our observation may relate these factors in osteoclast signaling and transcription. The overall goal of this project will be to elucidate the critical function of the Mi transcription factor in osteoclast development. The specific aims are 1) To Characterize Mi's expression and function during osteoclast development, 2) To examine the possible regulation of Mi via M-CSF receptor signaling and 3) To analyze potential genes transcriptionally regulated by Mi in osteoclasts. Mi expression and dimerization partners will be analyzed by immunohistochemistry, immunoprecipitation, and Western blot analysis with monoclonal and polyclonal antibodies that I have developed and characterized. Mi's potential role in M-CSF signaling will be assessed by analyzing the MAP kinase pathway and in vitro kinase assays using Mi or specific mutants as substrate. Variety of Mi expression constructs have been engineered including dominant negative mutants and will be employed to help identify target genes transcriptionally regulated by Mi in osteoclasts. Dr. David Fisher will supervise the project and head an advisory board of experts in signalling, bone biology, cellular physiology formed to provide additional guidance and aid in my transition to an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: MI--SIGNAL RESPONSIVE TRANSCRIPTION IN OSTEOCLASTS Principal Investigator & Institution: Fisher, David E. Associate Professor; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: The Microphthalmia (Mi) gene encodes one of the oldest recognized factors critical to osteoclast development and function. Mi is also required for development of the melanocyte lineage. The recently cloned Mi gene encodes a HLH-ZIP transcription factor, and is unique in its highly restricted tissue distribution. We have defined protein and DNA interactions of MI and found it to bind and potentially activate transcription off promoters containing its recognition element. We have recently examined an unusual rat mutant which displays severe osteoporosis which resolves with aging and shown that this results from a large deletion within Mi. We also discovered 3 dimerization partners of Mi (TFEB, TFEC, and TFE3) collectively called the "MiT" family. At least one of these other factors is present in the Mi-deficient osteoclasts of this rat strain, suggesting a general a general role of this family in osteoclast function and maturation. Our studies in melanocytes have also revealed that Mi is strongly activated by MAP kinase phosphorylation following cytokine stimulation. c-Kit signaling operates through activation of Mi in this fashion. We now also know that the mechanism of this activation is phospho-Mi selective recruitment of the transcriptional co-activators p300/CBP. Importantly, our current results suggest that Mi is similarly phosphorylated

16 Osteopetrosis

in response to cytokine signaling in osteoclasts, and this response (to factors such as interleukin 6 and M-CSF) could lie critically within a major pathway of osteoclast activation. The understanding of such pathways is clearly central to future goals of modulating osteoclast function in conditions such as osteoporosis. To further enhance our understanding of this factor and extend our analysis of its actions within osteoclasts, this grant proposes to: 1) systematically examine Mi'T protein temporal expression patterns in osteoclasts throughout development and aging, 2) derive viral vectors permitting up- or down-regulation of endogenous MiT factors in osteoclasts, and examine their consequences on osteoclast development and function, 3) define mechanistic relationships between Mi and osteoclast signaling pathways of importance in bone homeostasis including other genes implicated in osteopetrosis and cytokines of functional importance, and 4) identify transcriptional target genes for Mi in osteoclasts by testing "rational" candidates identified through sequence analysis of known promoters as well as a highly stringent differential display which requires up-regulation by wild type Mi, down- regulation by dominant negative Mi, as well as cytokinemediated Mi induction in the presence of cycloheximide. Through these studies we hope to gain insight into osteoclast biology through an understanding of Mi's central role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: NOVEL AUREOLIC ACID TYPE ANTITUMOR AGENTS Principal Investigator & Institution: Rohr, Jurgen; Professor; Pharmaceutical Sciences; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (provided by applicant):Mithramycin (MTM) is an aureolic acid antimicrobial and antitumor agent produced by various Streptomyces species including S. argillaceus, which has been used, e.g., for the treatment of testicular carcinoma. In addition, MTM is unique among anticancer agents in that it also has been used clinically to treat cancercaused malignant hypercalcemia and Paget's bone disease. However, MTM's bone marrow, hepatic, and renal toxicity limit its widespread clinical use. It is proposed to investigate various aspects of the biosynthesis of the antitumor and osteoclast-inhibiting agent mithramycin in order to develop analogs with increased therapeutic indices, which also may allow the separation of the two principal effects of MTM, (i) on cancer growth and (ii) on osteoclasts. This will lead to novel antitumor agents and/or to therapeutics against osteoporosis and other diseases related to bone growth disorders, and bears the potential for a novel gene therapy concept in future. Combinatorial biosynthetic methods will be used to provide an array of MTM analogs. For this, the biosynthetic pathway to MTM, which is dominated by a type II polyketide synthase (PKS), needs to be further characterized. Especially genes encoding enzymes responsible for the late biosynthetic steps, the post-PKS tailoring enzymes, particularly oxidoreductases and group transferases will be modified Resulting mutant strains will help to determine the series of events within the biosynthetic pathway and will characterize substrates and function of important enzymes in the MTM pathway. This information will be used to design novel compounds with specific activity-increasing functionality. In context with the mechanism of action of MTM on osteoclasts, we want to explore whether MTM derivatives can effect the expression of c-src, a proto-oncogene necessary for the osteoclastic bone resorption, following the novel hypothesis that MTM and its derivatives inhibit osteoclast bone resorption by blocking Sp 1 binding to the promoter region of the c-src proto-oncogene. The following three specific aims will be addressed: (1) To further characterize the biosynthetic pathway of mithramycin and to

Studies 17

develop new niithramycin derivatives through selective gene inactivation and product identification. Various group transferases and oxidoreductases will be investigated. In addition, the mtm genes will be recombined with promising deoxysugar biosynthesis, glycosyltransferase and oxygenase encoding genes from other pathways to develop novel niithramycin analogs modified in their saccharide and/or 0-atom pattern. (2) The two oxygenases of the MTM pathway, MtmOII and MtmOIV, will be investigated. The work on MtmOII, an early-acting oxygenase, will help to identify the missing link between the final PKS product and 4-demethylpremithramycinone, the earliest mithramycin precursor documented to date. Tetracyclic niithramycin analogs will be converted into their tricycic and expected more active counterparts by overexpressing oxygenase MtmOIV in the various glycosyltransferase deletion mutants. (3) To assay the binding properties of MTM and its novel analogs to the GC-rich elements in the c-myc and c-src promoters and their ability to prevent Sp 1 binding. Testing the high-affinity cmyc will follow thisand c-src binding compounds for inhibition of gene expression in human cancer cells and for their effects on growth and viability of normal and cancer cells. Finally, promising c-src inhibiting analogs will be analyzed for activity against osteoclastmediated bone resorption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: OPERATION OF AN INFRARED BEAMLINE DEDICATED TO STUDY OF BIO MEDICAL PROBLEMS Principal Investigator & Institution: Chance, Mark R. Professor; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001 Summary: As a model for examining the development of subchondral bone, we are examining the joints of mice who are osteopetrotic (op/op mice). In osteoporosis, reduced osteoclast formation prevents bone resorption, leading to a net overgrowth of bone. The op/op mouse is osteopetrotic due to an alteration in the CSF-1 (Colony Stimulating Factor-1) gene. This mutation, the insertion of a thymidine 262 base pairs downstream of the ATG start codon in the CSF-1 gene, leads to a frame shift and the introduction of a premature stop codon. As a result, the mutated gene encodes a truncated protein product of about 60 amino acids, which lacks biological activity. CSF-1 normally stimulates the differentiation of osteoclast progenitors into osteoclasts and may also regulate mature osteoclasts. In the op/op mouse, the lack of CSF-1 leads to osteopetrosis due to a marked reduction in osteoclast numbers; the bone produced cannot be resorbed. Studies in Dr. Stanley's lab and elsewhere have shown that either spontaneous aging or injections of human recombinant CSF-1 into op mice from 3 days of life, is capable of reverting diaphyseal bone (i.e. bone in the shaft of the femur) to more normal histology, but subchondral bone remains petrotic. Drs. Hamerman and Stanley will examine the macrophage and osteoclast populations over time in the subchondral and diaphyseal bone in aging and CSF-1 treated mice. In addition, the histologic state of the overlying articular cartilage will be examined to determine if petrotic subchondral bone is associated with degeneration of the overlying articular cartilage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTIVITY

OSTEOBLAST

STIMULATION

EFFECTS

ON

OSTEOCLAST

Principal Investigator & Institution: Sauders, Marnie M. Orthopaedics & Rehabilitation; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, PA 17033

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Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term goal of this research is to elucidate the mechanisms involved in implant-induced osteolysis and the effect(s) of mechanical loading on this process. Biological training proposed in this application augmented with the applicant's engineering background, would enable the applicant to complete the research proposed herein and develop future research aimed at osteolysis. The goal of the current application is to determine the role of the substrate in enhancing the mechanoresponsiveness of osteoblastic cells and the effects of stimulated soluble factors on osteoclastic cells. Specifically, we will determine if substrate contributes to cell flattening, cell networking and cell-cell communication by analyzing these factors in communication-competent and -deficient osteoblastic cell lines on artificial and native substrates. We will then determine if these factors contribute to the mechanoresponsiveness of osteoblastic cells by quantifying fluid flow-induced cell secreted levels of osteoprotegerin (OPG) and its ligand (RANKL). Finally, we will determine if enhanced osteoblastic responsiveness is coupled to an inhibition of osteoclastogenesis and functional osteoclastic activity by quantifying OPG, RANKL and bone resorption by osteoclasts in the presence and absence of stimulated media from the osteoblastic fluid flow studies. We propose that a native substrate, relative to an artificial substrate, contributes to the mechanoresponsiveness of osteoblastic cells by promoting cell flattening, cell networking and cell-cell communication. Furthermore, we propose that coupling mechanisms exist between osteoblastic and osteoclastic cells which enable the orchestration of bone formation and resorption and that stimulation of osteoblastic activity results in an upregulation of soluble factors promoting inhibition of osteoclastogenesis and osteoclastic activity. Future work will focus on the development of in situ mechanotransduction models incorporating bone substrates. Research in this area will illuminate the mechanisms by which normal cells sense and respond to mechanical loading and the effects of the milieu in this process. This is the first step in understanding the breakdown of these mechanisms associated with disease and altered loading environments. This work has several clinically relevant applications including implant- and metastatic-induced osteolysis, osteoporosis, osteopetrosis, fracture healing and functional tissue engineering. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RANK SIGNALING IN OSTEOCLAST DIFFERENTIATION & FUNCTION Principal Investigator & Institution: Feng, Xu; Pathology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Osteoclasts (OCs), the principal bone-resorbing cells, arise from hematopoietic precursors of monocyte-macrophage lineage upon stimulation of two key factors: M-CSF and RANKL (also known as OPGL/ODF/TRANCE). RANKL, identified as a member of TNF family, is a potent inducer of OC differentiation, activation and survival. RANKL exerts its effects by binding to its receptor RANK, identified as a member of TNF receptor superfamily, on OC precursors or mature OCs. Both RANKL-/- and RANK-/- mice develop osteopetrosis due to the failure to form OCs, indicating that RANK signaling is essential for differentiation. Furthermore, RANKL activates the resorptive function of the mature OCs and inhibits their apoptosis. Thus, RANKL is pivotal to generation, activation and survival of OCs. However, the specific motifs (residues) in the RANK cytoplasmic domain mediating OC differentiation, activation and survival have not been identified. We have developed a

Studies 19

tool which permits us to identify the specific motifs mediating these three effects. Using a retroviral technology, we expressed a chimeric receptor containing the extracellular domain of TNFR1 linked to the transmembrane and cytoplasmic domains of RANK in authentic OC precursors isolated from TNFR1/R2 double knock-out mice. Treatment of the chimera-expressing OC precursors with TNF-alpha as a RANKL surrogate, plus MCSF, generates OCs, indistinguishable from those induced by RANKL and M-CSF. Thus, using this chimeric protein approach, we are positioned to delineate the specific motifs in the RANK cytoplasmic domain mediating OC differentiation, activation and survival. Since members of TNF receptor superfamily transmit the intracellular signaling by binding intracellular adaptor proteins such as TRAFs, we hypothesize that RANK, as a member of the TNF receptor superfamily, initiates its signaling in OC differentiation, activation and survival by recruiting adaptor proteins, including TRAFs, to specific motifs in the RANK cytoplasmic domain. Our Specific Aims are to identify: (1) specific motifs in the RANK cytoplasmic domain mediating OC differentiation; (2) specific motifs in the RANK cytoplasmic domain mediating OC activation; and (3) specific motifs in the RANK cytoplasmic domain mediating OC survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: RANK/NF-KAPPAB SIGNALING IN CHONDROGENESIS Principal Investigator & Institution: Boyce, Brendan F. Professor; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Most of the skeleton forms by endochondral ossification in a highly regulated process in which skeletal elements are first laid down during embryogenesis in a cartilaginous framework. These cartilage elements are invaded by blood vessels and partly replaced by bone, laid down by bone forming osteoblasts and remodeled by bone destroying osteoclasts at epiphyseal growth plates, which form near the ends of the growing bones and control skeletal growth. Many genes have been identified during the past decade as regulators of this process, and mutation or deletion of them can result in various chondrodysplasias, including dwarfism. RANKL/RANK/NF- B signaling was shown to regulate osteoclastogenesis after deletion of these genes in mice led to osteopetrosis due to failure of osteoclast formation. Surprisingly, these knockout mice also have short limbs, but the role of this signaling pathway in endochondral ossification has not been studied in detail. In this proposal, we plan to obtain preliminary data that will provide definitive evidence of a role for this pathway in chondrogenesis and to develop an assay that will permit in vitro morphologic assessment of manipulation of this and other signaling pathways. Our Specific Aims are: 1) To determine the role of RANKL/RANK/NF- B signaling in chondrogenesis; 2) To determine the effects of absent RANK/NF- B signaling on chondrocyte gene expression. NF- B transcription factors regulate the expression of a variety of genes involved in numerous cell processes, including the early stages of limb development. Delineation of a specific role for these factors in endochondral ossification should open up a new field of investigation into the pathogenesis of the many forms of chondrodysplasia that to date do not yet have an identified molecular basis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

·

Project Title: FORMATION

RANK-ASSOCIATED

INHIBITOR

(RAIN)

IN

OSTEOCLAST

Principal Investigator & Institution: Darnay, Bryant G. Bioimmunotherapy; University of Texas Md Anderson Can Ctr Cancer Center Houston, TX 77030

20 Osteopetrosis

Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 29-MAR-2008 Summary: (provided by applicant): Receptor activator of NF-kappaB (RANK) and its ligand (RANKL, also known as TRANCE/ODF/OPGL) are essential mediators of osteoclastogenesis and have been implicated in various diseases, which include rheumatoid arthritis, osteoporosis, giant cell tumor of bone, Paget's disease, metastatic breast cancer, multiple myeloma, and familial expansile osteolysis. Osteoprotegerin (OPG, also known as OCIF/TR1) is a soluble, decoy receptor that inhibits RANKL from binding to its cell surface receptor RANK. Activation of signaling pathways by RANK is mediated through its interaction with tumor necrosis factor receptor-associated factors (TRAFs). Mice deleted of RANKL, RANK, or TRAF6 lack osteoclasts and develop severe osteopetrosis while mice lacking OPG develop osteoporosis. Thus, RANKL and OPG are the governing factors that regulate normal bone homeostasis. The cytoplasmic domain of RANK interacts with TRAF1, 2, 3, 5, and 6, and our laboratory described the distinct regions of RANK that interact with TRAF2, 5, and 6. In an effort to identify other factors that interact with the cytoplasmic domain of RANK, we used a yeast twohybrid approach and identified a novel protein, which we termed RAIN, for RANKAssociated Inhibitor, for its ability to inhibit RANKL-mediated osteoclast formation Both mouse and human cDNAs were cloned and contain an open reading frame of 241 and 242 residues, respectively. RAIN is a novel protein with no identifiable domains or motifs. RAIN coprecipitates with endogenous RANK in RAW264.7 (RAW) cells. Furthermore, RAIN interacts with TRAF2, TRAF5, and TRAF6 in RAW cells. To understand the function of RAIN, RAW cells stably expressing RAIN did not interfere with early RANKL signaling such as NF-kappaB, JNK, ERK, or p38 MAPK activation. However, RAIN expressing cells did not form multinucleated osteoclasts when stimulated with RANKL, although the cells were TRAP+ and the cell cycle inhibitor p27 was upregulated. Thus, it appears RAIN acts as a negative regulator of the fusion event during osteoclast differentiation. In support of this model, we established RAW cells stably expressing anti-sense RAIN. Surprisingly, we observed increased osteoclast number, which was observed as early as day 2. Additionally, RANKL treatment of RAW cells caused induction of RAIN mRNA and protein, which begins on day 2 and continues through day 5. Biochemical evidence suggests that RAIN may function by sequestering or preventing F-actin polymerizatio. Thus, we have identified a novel protein that interacts with RANK and TRAFs, and presumably controls the formation multi-nucleated osteoclasts. We propose to extend these studies to further our understanding of RAIN's function in osteoclastogenesis by pursing the following specific aims: (1) define the molecular interactions of RAIN and TRAFs; (2) determine the biochemical proteins of RAIN with respect to actin polymerization; and (3) determine the physiological role of RAIN by targeted gene disruption and transgenic mice expressing RAIN. The identification of RAIN and it function in controlling osteoclast formation will provide new insights into the mechanism of osteoclast formation and may provide a novel target for the development of pharmaceutical agents aimed at preventing unwanted bone destruction associated with metabolic bone disorders and cancers associated with osteolytic lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: REGULATION OF OSTEOCLASTOGENESIS BY TRANCE Principal Investigator & Institution: Choi, Yongwon; Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 28-FEB-2005

Studies 21

Summary: (Adapted from the Investigator's Abstract): Bone homeostasis is maintained by the balanced action of osteoblasts and osteoclasts. Osteoclasts, which are the cells that resorb bone, are derived from hematopoietic precursor cells. Osteoblasts induce precursor cells in the bone marrow to differentiate into osteoclasts by providing stimuli from two essential molecules: M-CSF and TRANCE. We initially cloned TRANCE (also known as RANKL, OPGL, and ODF) as a TNF family member, which is highly expressed in activated T cells. We recently demonstrated that TRANCE provides the costimulation required for proper T cell responses in vivo, thus establishing its pivotal role in the immune system. Recently, others found that TRANCE is also expressed in osteoblasts and works as an osteoclast differentiation factor such that soluble TRANCE, in conjunction with M-CSF, can substitute for stromal cells to induce osteoclast formation in vitro. In addition, we and others found that mice deficient in the TRANCE gene develop severe osteopetrosis due to defects in osteoclast differentiation, thus establishing that TRANCE is indeed an essential factor for osteoclast differentiation in vivo. We propose to extend these molecular genetic studies of the effect of TRANCE on osteoclast differentiation in vivo by pursuing the following specific aims in this revised application: (1) determining whether TRANCE expressed in cells other than osteoblasts, in particular resting T cells, can influence osteoclast differentiation, (2) determining the differential effect of TRANCE expressed in T cells vs. in osteoblasts on osteoclast differentiation, and (3) determining the potential mechanisms governing TRANCEinduced osteoclast differentiation. The knowledge gained from these studies will provide insights into how different cell types may regulate osteoclast differentiation, and how crosstalk between bone, bone marrow, and the immune system occurs. In addition, the studies will elucidate the potential mechanism of how TRANCE regulates osteoclast differentiation in vivo. These studies will, in turn, help to provide the molecular basis of and potential treatment for various bone lesions associated with abnormal T cell activation or lymphomas as well as for bone destruction associated with various other diseases such as arthritis and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ROLE OF PYK2 IN REGULATING OSTEOCLASTIC BONE RESORPTION Principal Investigator & Institution: Xiong, Wen-Cheng; Pathology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal of the proposed research is to understand molecular mechanisms of bone resorption, a process that requires osteoclast activation and is altered in multiple bone disorders such as osteopetrosis and osteoporosis. Osteoclastic activation is initiated by adhesion to the bone surface, followed by cytoskeletal rearrangement, formation of the sealing zone and polarized ruffled membrane, and directional secretion of acids and lysosomal enzymes in the resorbing surface. Osteoclasts attach to the extracellular matrix at podosomes. Podosomes are dot-like aggregations of actin that cluster in a ring around the cell periphery. They are similar to focal adhesions in fibroblasts. Changes in podosome assembly and disassembly allow osteoclast adhesion, migration, and bone resorption. Integrin-mediated signaling plays a key role in these processes. Integrin engagement triggers activation of proline-rich tyrosine kinase 2 (PYK2), an "adapter-like" tyrosine kinase that is related to focal adhesion kinase (FAK). PYK2 is highly expressed in osteoclasts and localized at podosomes and tight sealing zones in resorbing osteoclasts. PYK2 knockdown by antisense or knockout leads to defects on podosome formation and

22 Osteopetrosis

bone resorption, indicating that PYK2 plays a critical role in regulating actin cytoskeletal organization in osteoclasts. However, exactly how PYK2 regulates osteoclast function remains unclear. In this proposal, we will focus on how PYK2 regulates podosome assembly in osteoclasts. Using focal adhesions in fibroblasts as a model system, we found that overexpression of PYK2 induced "podosome-like" focal adhesions. We have studied mechanisms of PYK2 induced cytoskeletal reorganization and found that gelsolin, an actin binding protein that is important for actin filament formation in osteoclasts, is regulated by PYK2. Based on our preliminary results, we hypothesize that PYK2 functions in osteoclasts by regulating gelsolin. To test this hypothesis, we will: 1. Investigate the function of the PYK2-gelsolin interaction in osteoclasts.2. Determine whether gelsolin is a PYK2 substrate in osteoclasts.3. Determine whether and how PYK2 regulates the gelsolin-PIP2 binding Results of the proposed studies will provide insight into PYK2 signaling pathways in regulating osteoclastic functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: ROLE OF THE C-SRC PROTO-ONCOGENE IN OSTEOCLASTS Principal Investigator & Institution: Baron, Roland E. Orthopedics and Rehabilitation; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 15-JUL-1994; Project End 30-JUN-2005 Summary: (Adapted from the Investigator's Abstract): The goal of this once-revised competing renewal application is to pursue an ongoing research program identifying the function of c-src which, in the osteoclast, is required for bone resorption and is unique to c-src. The hypothesis that c-src may play a unique role in osteoclast function stems from three observations: First, deletion of the c-src proto-oncogene in the mouse leads to osteopetrosis without other apparent cellular defects. Second, the cellular defect induced by c-src gene deletion is cell autonomous. Third, the osteoclast not only expresses c-src at high levels but also other members of the Src family of non-receptor tyrosine kinases, implying that although present, they cannot compensate for src deletion in osteoclast function. During the first five years of this program, the applicant has made significant progress towards understanding the potential functions of c-src in bone resorption. However, despite the progress made, the mechanism(s) by which src deletion leads to a decrease in bone resorption is not yet definitively characterized. The most significant advances during the previous support period include: 1) the identification of the integrin alphaVbeta3 signaling pathway as the most likely to be affected by the absence of Src in the osteoclast, and 2) the characterization of the trimolecular complex comprising Pyk2, Src and Cbl as a key molecular element involved in the activation and de-activation of adhesion that is necessary for normal osteoclast mobility. These observations led to the development of a model for podosome assembly and disassembly, which now serves as the central working hypothesis to be tested in the coming years. The central concept that has emerged from these studies was the notion of the crucial importance of podosome assembly and disassembly in the process of osteoclastic bone resorption. The specific Aims of this revised application are therefore to: 1. Test the various steps of the podosome assembly-disassembly model through specific disruption of each presumed molecular interaction in the Pyk2-Src-Cbl complex, downstream of integrins in vitro. 2. When validated in vitro, generate transgenic mice expressing a selected number of the mutant Pyk2, Src or Cbl constructs targeted to the osteoclast by the TRAP promoter. 3. Further analyze the effects of knockouts and double knockouts of these molecules on osteoclast biology, adhesion, motility and bone resorption in vivo and in vitro. 4. Determine, which other molecules are associating with the Src complex upon adhesion.

Studies 23

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

Project Title: SRC STEROIDOGENESIS

TYROSINE

KINASE

REGULATES

GONADAL

Principal Investigator & Institution: Terranova, Paul F. Director & Professor; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 23-APR-1996; Project End 31-MAR-2006 Summary: Published studies from our lab reveal that blockage of Src tyrosine kinase enhances LH stimulated cAMP and androstenedione product in rat thecal- interstitial cells indicating the first potential role of this kinase in ovarian function. Preliminary data presented in this application reveal that Src knockout mice exhibit a significant reduction in the ability to form antral follicles during the prepubertal period, increased primordial follicular development. And enhanced responses to gonadotropins in vivo and in vitro. In addition, in wild type C57BL6 control mice, exogenous gonadotropins induce significant changes in ovarian Src kinase activity during follicular development and the periovulatory period. In the present studies, human and mouse theca-interstitial cells, and Src knockout mice will be used for physiological and a clinically related investigations on the role of Src in ovarian function. Because Src knockout mice exhibit osteopetrosis, stunted growth, post-weaning malnutrition due to the failure of tooth eruption, and early death, it is difficult to fully assess the impact of ovarian Src deficiency. Thus, the first aim proposes to transplant immature Src knockout ovaries (-/) into age matched wild type litter mates (+/+) in order to study the impact of ovarian specific Src depletion on ovarian function. In order to account for alterations in follicular development in the prepubertal period, the second aim will contrast and compare quantitative aspects of ovarian follicular develop in fetal, neonatal and prepubertal Src knockout mice with wild type littermates. The third aim will assess the in vitro effects of inhibition and activation of Src tyrosine kinase on LH-mediated stimulation of cAMP and androstenedione secretion in mouse (Src knockout and wild type) and human theca-interstitial cells using pharmacological and genetic approaches. In order to account for the increased gonadotropin responsiveness when the Src gene is deleted or its activity is blocked, the fourth aim will determine whether inhibition or activation of Src tyrosine kinase in mouse thecal interstitial cells and human theca cells alters LH/hCG receptor number and agonist-induced receptor internalization This project will provide new insight into the role of Src tyrosine kinase in regulating follicular development and gonadotropin-stimulate steroidogenesis in the ovary. The results from these studies may indicate new reasons for marked variations in gonadotropin responsiveness in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: TRANSCRIPTIONAL REGULATION OF OSTEOCLASTS BY MITF Principal Investigator & Institution: Lin, Yi-Ling;; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: Recent advances in bone biology have revolutionized dentistry. With better understanding of how osteoblasts respond to bone-forming signals, dentists now can use a variety of grafting materials to perform bone augmentation procedures and grow bone "de novo". In contrast, it is still largely unknown how osteoclasts regulate their activity in response to local factors. This knowledge is of great importance to the dental profession since so many dental diseases are directly or indirectly the result of

24 Osteopetrosis

unwanted osteoclast activation. One critical regulator of osteoclast activity is Microphthalmia transcription factor (Mitt). Mice carrying semidominant Mitf alleles exhibit various degrees of osteopetrosis, indicating Mitf is a promising tool for studying gene regulation in osteoclasts. The objective of the proposed study is to gain knowledge of the transcriptional regulation of osteoclasts by Mitf and three other family members, TFEB, TFEC and TFE3 (the four proteins form the "MiT" family). Since Mitf semidominant mutant mice exhibit an age-dependent phenotype, the chronological expression profiles of MiT proteins during osteoclast development will be examined since this would be consistent with functional rescue of Mitf by family members. MAPK and Rsk/PKA have previously been demonstrated to phosphorylate Mitf in melanocytes, which resulting in Mitf activation. To examine if similar processes occur in osteoclasts, recombinant MiT mutant viruses carrying disrupted MAPK and Rsk/PKA phosphorylation sites will be used, and the resulting phenotypic changes will be analyzed. Mitf has been found to regulate cytoskeletal changes in response to maturation signals during fetal osteoclast fusion. Overexpression of the individual MiT protein in fetal mi/mi osteoclasts (which do not fuse or form multinucleated giant cells) will be tested for the ability to rescue the fusion defect. Since Mitf may affect multinucleate giant cell formation by regulating the expression of molecules essential for osteoclast fusion, candidates known to be essential for this process (such as vitronectin receptor and osteopontin) will be examined for their relationship with Mitf. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen ·

Project Title: XRAY FOOTPRINTING OF GELSOLIN & ACTIN COMPLEX Principal Investigator & Institution: Maleknia, Simin D.; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2001 Summary: The unique strength and rigidity of bone arises from a combination of organic components (primarily collagen) and inorganic (mineral) components. Over a lifetime, bone is continuously remodeling itself. Old bone is eroded away in a tunnellike fashion by osteoclasts and new bone is deposited layer-by-layer in the tunnel by osteoblasts. From a cross-sectional view, these new layers of bone, collectively termed an osteon, appear as series of concentric circles through a microscope. A typical osteon measures ~200 ?m in diameter, where the youngest bone is at the center. In many diseased states of bone, there is an imbalance between bone production and resorption, resulting in overgrowth (osteopetrosis) or undergrowth (osteoporosis) of bone. To date, it is unclear whether the chemical composition of the bone in a diseased state is the same as normal bone. Using infrared micro-spectroscopy, we are able to visibly and chemically image individual osteons in terms of growth-, site-, and age-dependent variations in mineral content (i.e. carbonate, phosphate, acid phosphate), mineral crystallinity, and the content/nature of the organic matrix. A significant advantage of this technique over other chemical methods is that the bone does not need to be homogenized before testing; we are able to study cross-sectional samples of bone in situ at a resolution of 3-5 ?m. In this study, we present a comparison of human osteoporotic bone to osteopetrotic bone. Early results show some similarities and also significant differences between osteopetrotic and osteoporotic bone. For both diseased states Hof bone, the ratios of phosphate-to-collagen and carbonate-to-collagen Hconcentrations are similar and these ratios increases as bone matures H(from the center to the periphery of the osteon). Also for both, the Hphosphate ions (PO43-) are replaced by other anions such as carbonate H(CO32-) as bone ages, i.e. the hydroxyapatite becomes Hnon-

Studies 25

stoichiometric. However in contrast, we observe significantly Hmore CO32- substitution in osteoporotic bone than osteopetrotic bone Has the bone matures. 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 “osteopetrosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for osteopetrosis in the PubMed Central database: ·

Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. by Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, Moritz JD, Schu P, von Figura K. 1998 Nov 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24840

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Increased Induction of Osteopetrosis, but Unaltered Lymphomagenicity, by Murine Leukemia Virus SL3-3 after Mutation of a Nuclear Factor 1 Site in the Enhancer. by Ethelberg S, Tzschaschel BD, Luz A, Diaz-Cano SJ, Pedersen FS, Schmidt J. 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=113096

·

Linking osteopetrosis and pycnodysostosis: Regulation of cathepsin K expression by the microphthalmia transcription factor family. by Motyckova G, Weilbaecher KN, Horstmann M, Rieman DJ, Fisher DZ, Fisher DE. 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33293

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Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12deficient mice. by Kaifu T, Nakahara J, Inui M, Mishima K, Momiyama T, Kaji M, Sugahara A, Koito H, Ujike-Asai A, Nakamura A, Kanazawa K, Tan-Takeuchi K, Iwasaki K, Yokoyama WM, Kudo A, Fujiwara M, Asou H, Takai T. 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151867

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Osteopetrosis in Src-Deficient Mice is Due to an Autonomous Defect of Osteoclasts. by Lowe C, Yoneda T, Boyce BF, Chen H, Mundy GR, Soriano P. 1993 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46536

3 4

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

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

26 Osteopetrosis

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

“Superscan” in an autosomal-dominant benign form of osteopetrosis. Author(s): Kim S, Park CH, Kim B. Source: Clinical Nuclear Medicine. 2001 July; 26(7): 636-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11416752&dopt=Abstract

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A case of osteopetrosis with pelvic ectopic spleen: an unusual association. Author(s): Reisli I, Caliskan U, Tastekin G, Koc H, Acikgozoglu S, Aydogdu-Kiresi D, Aydin K. Source: Turk J Pediatr. 2001 July-September; 43(3): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592523&dopt=Abstract

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A comparative study of pycnodysostosis, cleidocranial dysostosis, osteopetrosis and acro-osteolysis. Author(s): Wolpowitz A, Matisonn A. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1974 May 18; 48(24): 1011-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4835770&dopt=Abstract

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A mild autosomal recessive form of osteopetrosis. Author(s): Kahler SG, Burns JA, Aylsworth AS. Source: American Journal of Medical Genetics. 1984 February; 17(2): 451-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6702897&dopt=Abstract

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

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·

A new approach to the study of the origin of genetic diseases: retroviral etiology of osteopetrosis. Author(s): Labat ML. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1991; 45(1): 23-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2043754&dopt=Abstract

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A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. Author(s): Borthwick KJ, Kandemir N, Topaloglu R, Kornak U, Bakkaloglu A, Yordam N, Ozen S, Mocan H, Shah GN, Sly WS, Karet FE. Source: Journal of Medical Genetics. 2003 February; 40(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566520&dopt=Abstract

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A review of inherited osteopetrosis in the mouse. Man and other mammals also considered. Author(s): Murphy HM. Source: Clinical Orthopaedics and Related Research. 1969 July-August; 65: 97-109. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4895800&dopt=Abstract

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A special form of constitutional narrowness of the cervical vertebral canal with thickened and hyperdense cortical bone of the posterior arch (osteopetrosis tardiva?). Author(s): Wackenheim A. Source: Acta Neurochirurgica. 1988; 92(1-4): 144-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3407469&dopt=Abstract

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A splice junction mutation in intron 2 of the carbonic anhydrase II gene of osteopetrosis patients from Arabic countries. Author(s): Hu PY, Roth DE, Skaggs LA, Venta PJ, Tashian RE, Guibaud P, Sly WS. Source: Human Mutation. 1992; 1(4): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1301935&dopt=Abstract

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Acute response of parathyroid hormone in congenital osteopetrosis. Author(s): Aarskog D, Asknes L, Haneberg B, Julshamn K. Source: Acta Paediatr Scand Suppl. 1979; 277: 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=232356&dopt=Abstract

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Adult osteopetrosis: study of two brothers. Author(s): Silvestrini G, Ferraccioli GF, Quaini F, Palummeri E, Bonucci E. Source: Appl Pathol. 1987; 5(3): 184-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3620211&dopt=Abstract

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Adult-type osteopetrosis presenting as carpal tunnel syndrome. Author(s): Rakic M, Elhosseiny A, Ramadan F, Iyer R, Howard RG, Gross L. Source: Arthritis and Rheumatism. 1986 July; 29(7): 926-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3741505&dopt=Abstract

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Age-resolving osteopetrosis: a rat model implicating microphthalmia and the related transcription factor TFE3. Author(s): Weilbaecher KN, Hershey CL, Takemoto CM, Horstmann MA, Hemesath TJ, Tashjian AH, Fisher DE. Source: The Journal of Experimental Medicine. 1998 March 2; 187(5): 775-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9480987&dopt=Abstract

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Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Author(s): Cleiren E, Benichou O, Van Hul E, Gram J, Bollerslev J, Singer FR, Beaverson K, Aledo A, Whyte MP, Yoneyama T, deVernejoul MC, Van Hul W. Source: Human Molecular Genetics. 2001 December 1; 10(25): 2861-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741829&dopt=Abstract

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Albers-Schonberg disease (osteopetrosis). Author(s): Natchiar G. Source: J All India Ophthalmol Soc. 1970 December; 18(4): 187-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5524575&dopt=Abstract

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Albers-Schonberg disease (osteopetrosis). Report of a case and review of the literature. Author(s): Smith NH. Source: Oral Surg Oral Med Oral Pathol. 1966 December; 22(6): 699-710. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5224178&dopt=Abstract

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Albers-Schonberg disease complicated with periodontal disease. Report of a case with 36-year history. Author(s): Svoboda PJ, Mendieta C, Reeve CM. Source: J Periodontol. 1983 October; 54(10): 592-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6580412&dopt=Abstract

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Albers-Schonberg's disease (osteopetrosis). A case with osteomyelitis of the maxilla. Author(s): Sofferman RA, Smith RO, English GM. Source: The Laryngoscope. 1971 January; 81(1): 36-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5091312&dopt=Abstract

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Allogeneic bone marrow transplantation in an osteopetrosis patient: first report in Thailand. Author(s): Hongeng S, Pakakasama S, Chuansumrit A, Rerkamnuaychoke B, Nitiyanunt P, Suthutvoravut U, Ungkanont A, Hathirat P. Source: Asian Pac J Allergy Immunol. 1998 December; 16(4): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219901&dopt=Abstract

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Allogeneic bone-marrow transplantation in infantile malignant osteopetrosis. Author(s): Sieff CA, Chessells JM, Levinsky RJ, Pritchard J, Rogers DW, Casey A, Muller K, Hall CM. Source: Lancet. 1983 February 26; 1(8322): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6131166&dopt=Abstract

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Animal models of osteopetrosis: the impact of recent molecular developments on novel strategies for therapeutic intervention. Author(s): Popoff SN, Schneider GB. Source: Molecular Medicine Today. 1996 August; 2(8): 349-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8796921&dopt=Abstract

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Antenatal diagnosis of lethal osteopetrosis. Author(s): Sen C, Madazli R, Aksoy F, Ocak V. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1995 April; 5(4): 278-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7600210&dopt=Abstract

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Apparent cure of a newborn with malignant osteopetrosis using prednisone therapy. Author(s): Iacobini M, Migliaccio S, Roggini M, Taranta A, Werner B, Panero A, Teti A. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 December; 16(12): 2356-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760852&dopt=Abstract

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Assay on the present clinical and nosographical aspects of osteopetrosis (AlbersSchonberg's disease): report of five cases. Author(s): Lovisetto P, Barese V, Marchi L. Source: Panminerva Medica. 1978 October-December; 20(4): 213-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=755968&dopt=Abstract

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Assessment of blood flow velocities in the ophthalmic arteries by transcranial Doppler sonography in osteopetrosis. Author(s): Iqbal J. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 February; 13(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9105750&dopt=Abstract

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Association of infantile neuroaxonal dystrophy and osteopetrosis: a rare autosomal recessive disorder. Author(s): Rees H, Ang LC, Casey R, George DH. Source: Pediatric Neurosurgery. 1995; 22(6): 321-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7577667&dopt=Abstract

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Association of intermediate osteopetrosis with poikiloderma. Author(s): Migliaccio S, Luciani M, Taranta A, De Rossi G, Minisola S, El Hachem M, Bosman C, De Felice L, Boldrini R, Corsi A, Bianco P, Teti A. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 May; 14(5): 834-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10320533&dopt=Abstract

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Association of osteopetrosis and vitamin D-resistant rickets. Author(s): Zamboni G, Cecchettin M, Marradi P, Foradori M, Zoppi G. Source: Helv Paediatr Acta. 1977 November; 32(4-5): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=217852&dopt=Abstract

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Association of severe autosomal recessive osteopetrosis and Dandy-Walker syndrome with agenesis of the corpus callosum. Author(s): Ben Hamouda H, Sfar MN, Braham R, Ben Salah M, Ayadi A, Soua H, Hamza H, Sfar MT. Source: Acta Orthop Belg. 2001 December; 67(5): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822087&dopt=Abstract

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Asynchronous asymmetric form of heterogeneous osteopetrosis: initial case expanded and a new case. Author(s): Young LW, Lachman RS. Source: Pediatric Radiology. 2001 January; 31(1): 48-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11200999&dopt=Abstract

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Autosomal dominant osteopetrosis (a family study). Author(s): Bollerslev J, Grodum E, Grontved A. Source: The Journal of Laryngology and Otology. 1987 October; 101(10): 1088-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3681134&dopt=Abstract

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Autosomal dominant osteopetrosis type II with “malignant” presentation: further support for heterogeneity? Author(s): Walpole IR, Nicoll A, Goldblatt J. Source: Clinical Genetics. 1990 October; 38(4): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2268972&dopt=Abstract

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Autosomal dominant osteopetrosis. Author(s): Bollerslev J, Mosekilde L. Source: Clinical Orthopaedics and Related Research. 1993 September; (294): 45-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358946&dopt=Abstract

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Autosomal dominant osteopetrosis: an otoneurological investigation of the two radiological types. Author(s): Bollerslev J, Grontved A, Andersen PE Jr. Source: The Laryngoscope. 1988 April; 98(4): 411-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3352441&dopt=Abstract

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Autosomal dominant osteopetrosis: bone metabolism and epidemiological, clinical, and hormonal aspects. Author(s): Bollerslev J. Source: Endocrine Reviews. 1989 February; 10(1): 45-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2666111&dopt=Abstract

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Autosomal dominant osteopetrosis: bone mineral measurements of the entire skeleton of adults in two different subtypes. Author(s): Grodum E, Gram J, Brixen K, Bollerslev J. Source: Bone. 1995 April; 16(4): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605703&dopt=Abstract

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Autosomal dominant osteopetrosis: report of a Norwegian family with radiographic or anamnestic findings differing from the generally accepted classification. Author(s): Lund-Sorensen N, Gudmundsen TE, Ostensen H. Source: Skeletal Radiology. 1997 March; 26(3): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9108228&dopt=Abstract

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Autosomal recessive osteopetrosis in Arab children. Author(s): Abdel-Al YK, Shabani IS, Lubani MM, al-Ghawabi MA, Ibrahim MD, alMohtaseb S, Duodin KI. Source: Annals of Tropical Paediatrics. 1994; 14(1): 59-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7516136&dopt=Abstract

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Autosomal recessive osteopetrosis: bone marrow imaging. Author(s): Elster AD, Theros EG, Key LL, Stanton C. Source: Radiology. 1992 February; 182(2): 507-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1732971&dopt=Abstract

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Autosomal recessive osteopetrosis: diagnosis, management, and outcome. Author(s): Wilson CJ, Vellodi A. Source: Archives of Disease in Childhood. 2000 November; 83(5): 449-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040159&dopt=Abstract

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Autosomal recessive osteopetrosis: variability of findings at diagnosis and during the natural course. Author(s): Gerritsen EJ, Vossen JM, van Loo IH, Hermans J, Helfrich MH, Griscelli C, Fischer A. Source: Pediatrics. 1994 February; 93(2): 247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8121736&dopt=Abstract

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Benign osteopetrosis, in a patient with sickle-cell beta+ (beta+) thalassaemia. Author(s): Kassimos D, Kalteziotis G, Alafakis G, Sinakos Z, Tegos C. Source: Clinical Rheumatology. 1995 July; 14(4): 471-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7586988&dopt=Abstract

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Benign osteopetrosis. Author(s): Rosenthall L. Source: Clinical Nuclear Medicine. 1990 June; 15(6): 412-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2354581&dopt=Abstract

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Benign osteopetrosis: a review of 42 cases showing two different patterns. Author(s): el-Tawil T, Stoker DJ. Source: Skeletal Radiology. 1993 November; 22(8): 587-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8291011&dopt=Abstract

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Benton E. Crawford radiograph of the month. Osteopetrosis. Author(s): Felefli S. Source: J Gt Houst Dent Soc. 1997 December; 69(5): 4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9571866&dopt=Abstract

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Bilateral acromial fractures in an infant with malignant osteopetrosis. Author(s): Coote JM, Steward CG, Grier DJ. Source: Clinical Radiology. 2000 January; 55(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10650116&dopt=Abstract

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Bilateral nonunited femoral neck fracture in a child with osteopetrosis. Author(s): Steinwender G, Hosny GA, Koch S, Grill F. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 1995; 4(2): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7670993&dopt=Abstract

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Bilateral visual improvement after unilateral optic canal decompression and cranial vault expansion in a patient with osteopetrosis, narrowed optic canals, and increased intracranial pressure. Author(s): Vanier V, Miller NR, Carson BS. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 September; 69(3): 405-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991652&dopt=Abstract

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Biochemical evidence of disturbed bone metabolism and calcium homeostasis in two types of autosomal dominant osteopetrosis. Author(s): Bollerslev J, Nielsen HK, Larsen HF, Mosekilde L. Source: Acta Med Scand. 1988; 224(5): 479-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3264447&dopt=Abstract

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Biochemical markers of bone metabolism in benign human osteopetrosis: a study of two types at baseline and during stimulation with triiodothyronine. Author(s): Bollerslev J, Ueland T, Grodum E, Haug E, Brixen K, Djoseland O. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1998 July; 139(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703375&dopt=Abstract

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Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I. Author(s): Bollerslev J, Mosekilde L, Nielsen HK, Mosekilde L. Source: Bone. 1989; 10(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2803852&dopt=Abstract

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Bisphosphonate-induced osteopetrosis. Author(s): Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Source: The New England Journal of Medicine. 2003 July 31; 349(5): 457-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890844&dopt=Abstract

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Blindness and brain atrophy in marble-bone disease (osteopetrosis). Author(s): Hamed MA, El-Nady FA, Hassan HM, El-Bassoussy EM, Abdel-Hamid T, ElGuindi S. Source: J Egypt Med Assoc. 1974; 57(7-8): 309-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4452771&dopt=Abstract

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Bone densitometry observations of osteopetrosis in response to bone marrow transplantation. Author(s): Kaplan FS, August CS, Dalinka MK, Karp J, Fallon MD, Haddad JG. Source: Clinical Orthopaedics and Related Research. 1993 September; (294): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358948&dopt=Abstract

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Bone densitometry of osteopetrosis in an adolescent girl. Author(s): Joyce JM, Malluche HH, Coon JS, Ryo UY. Source: Clinical Nuclear Medicine. 1990 January; 15(1): 48-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2306898&dopt=Abstract

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Bone marrow scintigraphy and MRI in a patient with osteopetrosis. Author(s): Otsuka N, Fukunaga M, Ono S, Morita K, Nagai K. Source: Clinical Nuclear Medicine. 1991 June; 16(6): 443-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1868660&dopt=Abstract

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Bone marrow scintigraphy with technetium-99m anti-NCA-95 to monitor therapy in malignant osteopetrosis. Author(s): Thelen MH, Eschmann SM, Moll-Kotowski M, Dopfer R, Bares R. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1998 June; 39(6): 1033-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627340&dopt=Abstract

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Bone marrow transplantation corrects osteopetrosis in the carbonic anhydrase II deficiency syndrome. Author(s): McMahon C, Will A, Hu P, Shah GN, Sly WS, Smith OP. Source: Blood. 2001 April 1; 97(7): 1947-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264157&dopt=Abstract

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Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group. Author(s): Gerritsen EJ, Vossen JM, Fasth A, Friedrich W, Morgan G, Padmos A, Vellodi A, Porras O, O'Meara A, Porta F, et al. Source: The Journal of Pediatrics. 1994 December; 125(6 Pt 1): 896-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7996361&dopt=Abstract

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Bone marrow transplantation for immunodeficiencies and osteopetrosis. Author(s): Fischer A. Source: Bone Marrow Transplantation. 1991; 7 Suppl 3: 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1855068&dopt=Abstract

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Bone marrow transplantation for infantile malignant osteopetrosis. Author(s): Solh H, Da Cunha AM, Giri N, Padmos A, Spence D, Clink H, Ernst P, Sakati N. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1995 November; 17(4): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7583393&dopt=Abstract

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Bone marrow transplantation in immunodeficiency and osteopetrosis. Author(s): Fischer A. Source: Bone Marrow Transplantation. 1989 December; 4 Suppl 4: 12-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2697421&dopt=Abstract

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Bone marrow transplantation in precocious osteopetrosis. Author(s): Nisbet NW. Source: British Medical Journal (Clinical Research Ed.). 1987 February 21; 294(6570): 4634. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3103728&dopt=Abstract

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Bone mineral density and laboratory evaluation of a type II autosomal dominant osteopetrosis carrier. Author(s): Takacs I, Cooper H, Weaver DD, Econs MJ. Source: American Journal of Medical Genetics. 1999 July 2; 85(1): 9-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10377007&dopt=Abstract

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Bone scintigraphy and densitometry in children with osteopetrosis. Author(s): el-Desouki M, al Herbish A, al Rasheed S, al Jurayyan N. Source: Clinical Nuclear Medicine. 1995 December; 20(12): 1061-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8674291&dopt=Abstract

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Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985. Author(s): Fischer A, Griscelli C, Friedrich W, Kubanek B, Levinsky R, Morgan G, Vossen J, Wagemaker G, Landais P. Source: Lancet. 1986 November 8; 2(8515): 1080-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2877234&dopt=Abstract

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Bone-marrow transplantation in osteopetrosis. Author(s): Reeves JD. Source: Lancet. 1978 April 29; 1(8070): 933-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=76865&dopt=Abstract

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Bone-marrow transplantation in osteopetrosis. Author(s): Nisbet NW, Menage J, Loutit JF. Source: Lancet. 1977 December 10; 2(8050): 1236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=73939&dopt=Abstract

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Bone-marrow transplantation in osteopetrosis. Author(s): Ballet JJ, Griscelli C, Coutris C, Milhaud G, Maroteaux P. Source: Lancet. 1977 November 26; 2(8048): 1137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=73050&dopt=Abstract

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Calcitriol for congenital osteopetrosis. Author(s): Blazar BR, Fallon MD, Teitelbaum SL, Ramsay NK, Brown DM. Source: The New England Journal of Medicine. 1984 July 5; 311(1): 55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6547208&dopt=Abstract

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Calcium mobilization in osteopetrosis. Author(s): Morrow G 3rd, Barness LA, Fost A, Rasmussen H. Source: Am J Dis Child. 1967 August; 114(2): 161-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4951540&dopt=Abstract

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Campath-1M antibodies for T cell depletion of haploidentical marrow transplanted to children with malignant osteopetrosis. Author(s): Fasth A, Porras O, Baltorano A, Carrillo J, Gonzales L, Odio C, de los Angeles Umana M. Source: Prog Clin Biol Res. 1992; 377: 399-403. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1438436&dopt=Abstract

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Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Author(s): Sly WS, Hewett-Emmett D, Whyte MP, Yu YS, Tashian RE. Source: Proceedings of the National Academy of Sciences of the United States of America. 1983 May; 80(9): 2752-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6405388&dopt=Abstract

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Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Author(s): Sly WS, Whyte MP, Sundaram V, Tashian RE, Hewett-Emmett D, Guibaud P, Vainsel M, Baluarte HJ, Gruskin A, Al-Mosawi M, et al. Source: The New England Journal of Medicine. 1985 July 18; 313(3): 139-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3925334&dopt=Abstract

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Carbonic anhydrase II deficiency syndrome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification. Author(s): Ohlsson A, Cumming WA, Paul A, Sly WS. Source: Pediatrics. 1986 March; 77(3): 371-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3081869&dopt=Abstract

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Case report 278. Osteopetrosis (tarsa type) with hemorrhagic cyst of the right sixth rib (proved) and the left second rib (presumptive). Author(s): Greene GS, Bonakdarpour A, Levy W. Source: Skeletal Radiology. 1984; 12(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6474222&dopt=Abstract

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Case report 668. Carbonic anhydrase II deficiency syndrome (osteopetrosis associated with renal tubular acidosis and cerebral calcification). Author(s): Schwartz GJ, Brion LP, Corey HE, Dorfman HD. Source: Skeletal Radiology. 1991; 20(6): 447-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1925679&dopt=Abstract

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Case report 718. Osteopetrosis with carbonic anhydrase II deficiency. Author(s): Eddy R, Resendes M, Genant H. Source: Skeletal Radiology. 1992; 21(2): 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1566113&dopt=Abstract

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Case report 746: Osteopetrosis. Author(s): Cook PF, Moore SG. Source: Skeletal Radiology. 1992; 21(6): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1523437&dopt=Abstract

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Case report: myelopathy secondary to congenital osteopetrosis of the cervical spine. Author(s): McCleary L, Rovit RL, Murali R. Source: Neurosurgery. 1987 March; 20(3): 487-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3574628&dopt=Abstract

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Centrifugal osteopetrosis: appendicular sclerosis with relative sparing of the vertebrae. Author(s): Kovacs CS, Lambert RG, Lavoie GJ, Siminoski K. Source: Skeletal Radiology. 1995 January; 24(1): 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7709248&dopt=Abstract

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Cerebrovascular occlusive complications in osteopetrosis major. Author(s): Wilms G, Casaer P, Alliet P, Demaerel P, Smet M, Baert AL. Source: Neuroradiology. 1990; 32(6): 511-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2287383&dopt=Abstract

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Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive osteopetrosis. Author(s): Campos-Xavier AB, Saraiva JM, Ribeiro LM, Munnich A, Cormier-Daire V. Source: Human Genetics. 2003 February; 112(2): 186-9. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522560&dopt=Abstract

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Chorioretinal degeneration in infantile malignant osteopetrosis. Author(s): Ruben JB, Morris RJ, Judisch GF. Source: American Journal of Ophthalmology. 1990 July 15; 110(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2368817&dopt=Abstract

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Circulating macrophage colony-stimulating factor is not reduced in malignant osteopetrosis. Author(s): Orchard PJ, Dahl N, Aukerman SL, Blazar BR, Key LL Jr. Source: Experimental Hematology. 1992 January; 20(1): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1577090&dopt=Abstract

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Circulating myeloid and erythroid progenitor cells in malignant osteopetrosis. Author(s): Marcus JR, Fibach E, Aker M. Source: Acta Haematologica. 1982; 67(3): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6805205&dopt=Abstract

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Circulating thrombopoietin levels in a neonate with osteopetrosis. Author(s): Colarizi P, Fiorucci P, Roggini M, Papoff P. Source: Pediatrics. 1999 March; 103(3): 700-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10189304&dopt=Abstract

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c-kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease. Author(s): Reinacher-Schick A, Petrasch S, Longley BJ, Teschendorf C, Graeven U, Schmiegel W. Source: Annals of Hematology. 1998 September; 77(3): 131-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9797083&dopt=Abstract

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Clinical and pathological observations on a case of newborn osteopetrosis. Author(s): Solcia E, Rondini G, Capella C. Source: Helv Paediatr Acta. 1968 December; 23(6): 650-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5717696&dopt=Abstract

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Clinical quiz. Osteopetrosis with carbonic anhydrase II deficiency. Author(s): Flynn MT, Gill DG. Source: Pediatric Nephrology (Berlin, Germany). 1996 February; 10(1): 125-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8611338&dopt=Abstract

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Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones. Author(s): Bollerslev J, Thomas S, Grodum E, Brixen K, Djoseland O. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1995 November; 133(5): 557-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581985&dopt=Abstract

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Complete visual recovery in osteopetrosis by early optic nerve decompression. Author(s): Hwang JM, Kim IO, Wang KC. Source: Pediatric Neurosurgery. 2000 December; 33(6): 328-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182645&dopt=Abstract

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Congenital osseous dysplasias. Case reports of osteopetrosis and pycnodysostosis in Ibadan, Nigeria. Author(s): Kolawole TM. Source: West Afr Med J Niger Pract. 1971 April; 20(2): 233-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5581943&dopt=Abstract

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Congenital osteopetrosis: an unusual cause of hydrocephalus. Author(s): Baird PA, Robinson GC, Hardwick DF, Sovereign AE. Source: Can Med Assoc J. 1968 February 17; 98(7): 362-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5639643&dopt=Abstract

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Congenital osteopetrosis--a failure of normal resorptive mechanisms of bone. Author(s): Fraser D, Kooh SW, Cherian AG. Source: Calcif Tissue Res. 1968; : Suppl: 52. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5721076&dopt=Abstract

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Congenital stationary nightblindness in a patient with osteopetrosis. Author(s): Matsui Y, Okinami S, Oono S, Matsui M. Source: The British Journal of Ophthalmology. 1995 December; 79(12): 1142-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8562556&dopt=Abstract

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Correction of anaemia and thrombocytopenia in a case of adult type I osteopetrosis with recombinant human erythropoietin (rHuEPO). Author(s): Meletis J, Samarkos M, Michali E, Vavourakis S, Meletis C, Poziopoulos C, Stavrogianni N, Konstantopoulos K, Vaiopoulos G, Yataganas X, et al. Source: British Journal of Haematology. 1995 April; 89(4): 911-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7772533&dopt=Abstract

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Cortical bone osteocalcin content and matrix composition in autosomal dominant osteopetrosis type I. Author(s): Bollerslev J, Marks SC Jr, Mosekilde L, Lian JB, Stein GS, Mosekilde L. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1994 June; 130(6): 592-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8205260&dopt=Abstract

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Cortical bone remodeling in autosomal dominant osteopetrosis: a study of two different phenotypes. Author(s): Brockstedt H, Bollerslev J, Melsen F, Mosekilde L. Source: Bone. 1996 January; 18(1): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8717539&dopt=Abstract

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Cranial CT of autosomal recessive osteopetrosis. Author(s): Bartynski WS, Barnes PD, Wallman JK. Source: Ajnr. American Journal of Neuroradiology. 1989 May-June; 10(3): 543-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2501985&dopt=Abstract

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Cranial imaging in autosomal recessive osteopetrosis. Part I. Facial bones and calvarium. Author(s): Elster AD, Theros EG, Key LL, Chen MY. Source: Radiology. 1992 April; 183(1): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1549658&dopt=Abstract

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Cranial imaging in autosomal recessive osteopetrosis. Part II. Skull base and brain. Author(s): Elster AD, Theros EG, Key LL, Chen MY. Source: Radiology. 1992 April; 183(1): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1549660&dopt=Abstract

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Cranial MR imaging of osteopetrosis. Author(s): Cure JK, Key LL, Goltra DD, VanTassel P. Source: Ajnr. American Journal of Neuroradiology. 2000 June-July; 21(6): 1110-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871023&dopt=Abstract

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Cranial osteopetrosis: MR findings. Author(s): Demirci A, Sze G. Source: Ajnr. American Journal of Neuroradiology. 1991 July-August; 12(4): 781-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1882766&dopt=Abstract

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Craniofacial abnormalities in osteopetrosis with precocious manifestations: report of a case with serial cephalometric roentgenograms. Author(s): Friede H, Manaligod JR, Rosenthal IM. Source: Journal of Craniofacial Genetics and Developmental Biology. 1985; 5(3): 247-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4044788&dopt=Abstract

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Craniometaphyseal dysplasia and osteopetrosis tarda. A rare combination of bone dysplastic changes. Author(s): Hurwitz RA. Source: J Med Soc N J. 1970 February; 67(2): 74-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5262886&dopt=Abstract

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Creatine kinase brain isoenzyme in infantile osteopetrosis. Author(s): Hiroyama Y, Miike T, Sugino S, Taku K. Source: Pediatric Neurology. 1987 January-February; 3(1): 54-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3508049&dopt=Abstract

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Cytophilic immunoglobulin G binding on neutrophils from a child with malignant osteopetrosis who developed fatal acute respiratory distress mimicking transfusionrelated acute lung injury. Author(s): Madyastha PR, Jeter EK, Key LL Jr. Source: American Journal of Hematology. 1996 November; 53(3): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895692&dopt=Abstract

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Dacryocystorhinostomy in osteopetrosis. Author(s): Orengo SD, Patrinely JR. Source: Ophthalmic Surg. 1991 July; 22(7): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1891185&dopt=Abstract

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Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I. Author(s): Grodum E, Kvetny J, Bollerslev J. Source: Life Sciences. 1991; 48(21): 2027-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2034033&dopt=Abstract

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Defective lymphocyte glycosidases in the macrophage activation cascade of juvenile osteopetrosis. Author(s): Yamamoto N, Naraparaju VR, Orchard PJ. Source: Blood. 1996 August 15; 88(4): 1473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8695868&dopt=Abstract

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Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Author(s): Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson AK, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A. Source: Nature Genetics. 2000 July; 25(3): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10888887&dopt=Abstract

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Degenerative osteoarthritis associated with osteopetrosis. Author(s): Cameron HU, Dewar FP. Source: Clinical Orthopaedics and Related Research. 1977; (127): 148-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=912970&dopt=Abstract

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Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant. Author(s): Lajeunesse D, Busque L, Menard P, Brunette MG, Bonny Y. Source: The Journal of Clinical Investigation. 1996 October 15; 98(8): 1835-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8878435&dopt=Abstract

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Dental changes in osteopetrosis. Author(s): Dick HM, Simpson WJ. Source: Oral Surg Oral Med Oral Pathol. 1972 September; 34(3): 408-16. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4505753&dopt=Abstract

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Dental development after successful treatment of infantile osteopetrosis with bone marrow transplantation. Author(s): Jalevik B, Fasth A, Dahllof G. Source: Bone Marrow Transplantation. 2002 March; 29(6): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960278&dopt=Abstract

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Developmental spectrum of children with congenital osteopetrosis. Author(s): Charles JM, Key LL. Source: The Journal of Pediatrics. 1998 February; 132(2): 371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9506663&dopt=Abstract

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Diagnosis of osteopetrosis (Albers-Schonberg) by Jamshidi needle biopsy. Author(s): Grouls V. Source: Human Pathology. 1981 February; 12(2): 198-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7216220&dopt=Abstract

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Difficult tracheal intubation of a patient with cervical fracture due to osteopetrosis. Author(s): Basaranoglu G, Erden V. Source: Paediatric Anaesthesia. 2001 November; 11(6): 745-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696156&dopt=Abstract

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Distal phalangeal resorption in an adult with infantile malignant osteopetrosis: a case report. Author(s): McCulloch PC, Athanasian EA. Source: The Journal of Hand Surgery. 1998 January; 23(1): 162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9523972&dopt=Abstract

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Dominant osteopetrosis. Author(s): Siggers DC. Source: Birth Defects Orig Artic Ser. 1974; 10(12): 501-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4461084&dopt=Abstract

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Dominant osteopetrosis: findings in a 12 year-old boy. Author(s): Kukla LF. Source: Clinical Pediatrics. 1977 September; 16(9): 846-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=891092&dopt=Abstract

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Dual-energy x-ray absorptiometry in osteopetrosis. Author(s): Adler IN, Stine KC, Kurtzburg J, Kinder DL, Cox KS, Lensing SY, Seibert JJ. Source: Southern Medical Journal. 2000 May; 93(5): 501-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10832951&dopt=Abstract

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Early VEP and ERG evidence of visual dysfunction in autosomal recessive osteopetrosis. Author(s): Thompson DA, Kriss A, Taylor D, Russell-Eggitt I, Hodgkins P, Morgan G, Vellodi A, Gerritsen EJ. Source: Neuropediatrics. 1998 June; 29(3): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706624&dopt=Abstract

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Effect of parathyroid hormone on vitamin D metabolism in osteopetrosis. Author(s): Aarskog D, Aksnes L, Markestad T. Source: Pediatrics. 1981 July; 68(1): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6264377&dopt=Abstract

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Elevated levels of creatine kinase BB isoenzyme in three patients with adult osteopetrosis. Author(s): Yoneyama T, Fowler HL, Pendleton JW, Sforza PP, Lui CY, Iranmanesh A, Gerard RD. Source: The New England Journal of Medicine. 1989 May 11; 320(19): 1284-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2710212&dopt=Abstract

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Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II. Author(s): Gram J, Antonsen S, Horder M, Bollerslev J. Source: Calcified Tissue International. 1991 June; 48(6): 438-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070279&dopt=Abstract

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Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II--a family study. Author(s): Yoneyama T, Fowler HL, Pendleton JW, Sforza PP, Gerard RD, Lui CY, Eldridge TH, Iranmanesh A. Source: Clinical Genetics. 1992 July; 42(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1516225&dopt=Abstract

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Enforced expression of Bcl-2 in monocytes rescues macrophages and partially reverses osteopetrosis in op/op mice. Author(s): Lagasse E, Weissman IL. Source: Cell. 1997 June 27; 89(7): 1021-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9215625&dopt=Abstract

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Evaluation of carbonic anhydrase isozymes in disorders involving osteopetrosis and/or renal tubular acidosis. Author(s): Sly WS, Sato S, Zhu XL. Source: Clinical Biochemistry. 1991 August; 24(4): 311-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1959222&dopt=Abstract

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Evidence for continuous basel generation of GC-MAF: absence in infantile osteopetrosis and restoration after bone marrow transplant. Author(s): Datta HK, Cook DB, Kanan RM. Source: Blood. 1999 June 1; 93(11): 4026-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10383196&dopt=Abstract

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Extramedullary hematopoiesis assessment in a patient with osteopetrosis. Author(s): Caluser C, Scott A, Macapinlac H, Yeh S, Rosenfelt N, Farid B, Abdel-Dayem HM, Larson SM, Kalaigian H. Source: Clinical Nuclear Medicine. 1995 January; 20(1): 75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7895447&dopt=Abstract

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Facial nerve dysfunction in osteopetrosis. Author(s): Dort JC, Pollak A, Fisch U. Source: The Laryngoscope. 1994 April; 104(4): 517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8164495&dopt=Abstract

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Facial nerve dysfunction in osteopetrosis. Author(s): Benecke JE Jr. Source: The Laryngoscope. 1993 May; 103(5): 494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8483364&dopt=Abstract

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Facial palsy in osteopetrosis. Relief by endotemporal decompression. Author(s): Yarington CT Jr, Sprinkle PM. Source: Jama : the Journal of the American Medical Association. 1967 November 6; 202(6): 549. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6072325&dopt=Abstract

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Failure of calcitriol treatment in a patient with malignant osteopetrosis. Author(s): van Lie Peters EM, Aronson DC, Everts V, Dooren LJ. Source: European Journal of Pediatrics. 1993 October; 152(10): 818-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8223784&dopt=Abstract

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Failure to diagnose osteopetrosis in utero. Author(s): Golbus MS, Koerper MA, Hall BD. Source: Lancet. 1976 December 4; 2(7997): 1246. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=63065&dopt=Abstract

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Familial osteopetrosis with coxa vara. A case report. Author(s): King RE, Lovejoy JF Jr. Source: The Journal of Bone and Joint Surgery. American Volume. 1973 March; 55(2): 381-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4696169&dopt=Abstract

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Fatal overwhelming postsplenectomy sepsis following autologous splenic transplantation in severe congenital osteopetrosis. Author(s): Tesluk GC, Thomas CG Jr, Benjamin JT, McMillan CW. Source: Journal of Pediatric Surgery. 1984 June; 19(3): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6747787&dopt=Abstract

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Femoral fractures in osteopetrosis: case reports. Author(s): Gupta R, Gupta N. Source: The Journal of Trauma. 2001 November; 51(5): 997-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706352&dopt=Abstract

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Femoral neck fracture in a child with autosomal dominant osteopetrosis. Author(s): Greene WB, Torre BA. Source: Journal of Pediatric Orthopedics. 1985 July-August; 5(4): 483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4019766&dopt=Abstract

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Fetal haemoglobin in early malignant osteopetrosis. Author(s): Schiliro G, Musumeci S, Pizzarelli G, Russo A, Marinucci M, Tentori L, Russo G. Source: British Journal of Haematology. 1978 March; 38(3): 339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=638082&dopt=Abstract

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First case of bone resorption evoked by bone marrow transplantation in a human patient with osteopetrosis. Author(s): Lamendin H. Source: Mater Med Pol. 1979 January-March; 11(1): 67-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=384102&dopt=Abstract

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Fluorosis, osteopetrosis, and ectopic calcification. Author(s): de Vernejoul MC. Source: Current Opinion in Rheumatology. 1990 February; 2(1): 44-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2223455&dopt=Abstract

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Focal sclerosing osteomyelitis/focal periapical osteopetrosis: radiographic patterns. Author(s): Eversole LR, Stone CE, Strub D. Source: Oral Surg Oral Med Oral Pathol. 1984 October; 58(4): 456-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6593677&dopt=Abstract

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Formation of non-resorbing osteoclasts from peripheral blood mononuclear cells of patients with malignant juvenile osteopetrosis. Author(s): Helfrich MH, Gerritsen EJ. Source: British Journal of Haematology. 2001 January; 112(1): 64-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167785&dopt=Abstract

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Fracture callus in osteopetrosis. Author(s): de Palma L, Tulli A, Maccauro G, Sabetta SP, del Torto M. Source: Clinical Orthopaedics and Related Research. 1994 November; (308): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7955707&dopt=Abstract

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Fracture patterns in malignant osteopetrosis (Albers-Schonberg disease). Author(s): Dahl N, Holmgren G, Holmberg S, Ersmark H. Source: Archives of Orthopaedic and Trauma Surgery. 1992; 111(2): 121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1562422&dopt=Abstract

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Fracture patterns in two types of autosomal-dominant osteopetrosis. Author(s): Bollerslev J, Andersen PE Jr. Source: Acta Orthopaedica Scandinavica. 1989 February; 60(1): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2929279&dopt=Abstract

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Free fibular flap reconstruction in mandibular osteopetrosis. Author(s): Eppley BL, Coleman JJ 3rd. Source: The Journal of Craniofacial Surgery. 2001 July; 12(4): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11482622&dopt=Abstract

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Further evidence for genetic heterogeneity within type II autosomal dominant osteopetrosis. Author(s): Benichou OD, Benichou B, Copin H, De Vernejoul MC, Van Hul W. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2000 October; 15(10): 1900-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11028441&dopt=Abstract

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Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis. Author(s): Taranta A, Migliaccio S, Recchia I, Caniglia M, Luciani M, De Rossi G, Dionisi-Vici C, Pinto RM, Francalanci P, Boldrini R, Lanino E, Dini G, Morreale G, Ralston SH, Villa A, Vezzoni P, Del Principe D, Cassiani F, Palumbo G, Teti A. Source: American Journal of Pathology. 2003 January; 162(1): 57-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507890&dopt=Abstract

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Glycosaminoglycans of human bone tissue. II. Chondroitin sulphate pattern of femoral cortex, medulla and epiphyseal plate in osteopetrosis. Author(s): Vejlens L. Source: Calcif Tissue Res. 1972; 9(1): 54-66. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4259680&dopt=Abstract

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Granulopoiesis in osteopetrosis. Author(s): Ragab AH, Ducos F, Crist WM, Duck SC. Source: The Journal of Pediatrics. 1975 September; 87(3): 422-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1165523&dopt=Abstract

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Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. Author(s): Chalhoub N, Benachenhou N, Rajapurohitam V, Pata M, Ferron M, Frattini A, Villa A, Vacher J. Source: Nature Medicine. 2003 April; 9(4): 399-406. Epub 2003 March 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627228&dopt=Abstract

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Growth hormone and IGF1 profile in short children with osteopetrosis. Author(s): al Herbish AS, al Jarallah A, al Jurayyan NA, abo Bakr AM, al Rasheed SA, Mahdi AH. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1994 February; 17(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8174311&dopt=Abstract

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Haploidentical bone marrow transplantation for osteopetrosis. Author(s): Orchard PJ, Dickerman JD, Mathews CH, Frierdich S, Hong R, Trigg ME, Shahidi NT, Finlay JL, Sondel PM. Source: Am J Pediatr Hematol Oncol. 1987 Winter; 9(4): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3326419&dopt=Abstract

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Haploidentical transplantation for osteopetrosis gives high engraftment rate, but low event-free survival. Author(s): Fasth A, Porras O, Arguedas O, Odio C, Umana M, Baltorano A, Carrillo J, Gonzales L. Source: Immunodeficiency. 1993; 4(1-4): 325. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167727&dopt=Abstract

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Head and neck manifestations of malignant osteopetrosis. Author(s): Wong ML, Balkany TJ, Reeves J, Jafek BW. Source: Otolaryngology. 1978 July-August; 86(4 Pt 1): Orl-585-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=112552&dopt=Abstract

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Hematopoietic stem cell transplantation for infantile osteopetrosis. Author(s): Eapen M, Davies SM, Ramsay NK, Orchard PJ. Source: Bone Marrow Transplantation. 1998 November; 22(10): 941-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849690&dopt=Abstract

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Heterogeneity of autosomal dominant osteopetrosis. Author(s): Andersen PE Jr, Bollerslev J. Source: Radiology. 1987 July; 164(1): 223-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3588909&dopt=Abstract

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High dose intravenous methylprednisolone in treatment of recessive osteopetrosis. Author(s): Ozsoylu S. Source: Archives of Disease in Childhood. 1987 February; 62(2): 214-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3827310&dopt=Abstract

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Higher osteoclastic demineralization and highly mineralized cement lines with osteocalcin deposition in a mandibular cortical bone of autosomal dominant osteopetrosis type II: ultrastructural and undecalcified histological investigations. Author(s): Semba I, Ishigami T, Sugihara K, Kitano M. Source: Bone. 2000 September; 27(3): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962350&dopt=Abstract

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Histomorphometric and immunocytochemical studies of src-related osteopetrosis. Author(s): Boyce BF, Chen H, Soriano P, Mundy GR. Source: Bone. 1993 May-June; 14(3): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7689855&dopt=Abstract

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HLA-haploidentical blood progenitor cell transplantation in osteopetrosis. Author(s): Schulz AS, Classen CF, Mihatsch WA, Sigl-Kraetzig M, Wiesneth M, Debatin KM, Friedrich W, Muller SM. Source: Blood. 2002 May 1; 99(9): 3458-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964318&dopt=Abstract

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Host defense in infantile osteopetrosis. Author(s): Reeves JD, August CS, Humbert JR, Weston WL. Source: Pediatrics. 1979 August; 64(2): 202-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=471611&dopt=Abstract

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Human autosomal recessive osteopetrosis maps to 11q13, a position predicted by comparative mapping of the murine osteosclerosis (oc) mutation. Author(s): Heaney C, Shalev H, Elbedour K, Carmi R, Staack JB, Sheffield VC, Beier DR. Source: Human Molecular Genetics. 1998 September; 7(9): 1407-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700194&dopt=Abstract

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Human malignant osteopetrosis: pathophysiology, management and the role of bone marrow transplantation. Author(s): Fasth A, Porras O. Source: Pediatric Transplantation. 1999; 3 Suppl 1: 102-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587979&dopt=Abstract

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Human osteopetrosis and other sclerosing disorders: recent genetic developments. Author(s): de Vernejoul MC, Benichou O. Source: Calcified Tissue International. 2001 July; 69(1): 1-6. Epub 2001 June 05. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685426&dopt=Abstract

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Human osteopetrosis: a histological, ultrastructural, and biochemical study. Author(s): Shapiro F, Glimcher MJ, Holtrop ME, Tashjian AH Jr, Brickley-Parsons D, Kenzora JE. Source: The Journal of Bone and Joint Surgery. American Volume. 1980 April; 62(3): 38499. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6245094&dopt=Abstract

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Hypogonadotropic hypogonadism from osteopetrosis. Author(s): Mazur J, Wortsman J. Source: Clinical Orthopaedics and Related Research. 1982 January-February; (162): 2026. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7067216&dopt=Abstract

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Ichthyosis and osteopetrosis. Author(s): Dowd PM, Munro DD. Source: Journal of the Royal Society of Medicine. 1983 May; 76(5): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6864708&dopt=Abstract

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Images and diagnoses. Autosomal recessive form of osteopetrosis. Author(s): Caksen H, Odabas D. Source: The West Indian Medical Journal. 2001 September; 50(3): 223, 248. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769030&dopt=Abstract

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Imaging of malignant infantile osteopetrosis before and after bone marrow transplantation. Author(s): Cheow HK, Steward CG, Grier DJ. Source: Pediatric Radiology. 2001 December; 31(12): 869-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727023&dopt=Abstract

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Imaging rounds #110. Osteopetrosis. Author(s): Geissler WB, Terral TG. Source: Orthop Rev. 1991 December; 20(12): 1099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1771107&dopt=Abstract

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Importance of neurological assessment before bone marrow transplantation for osteopetrosis. Author(s): Abinun M, Newson T, Rowe PW, Flood TJ, Cant AJ. Source: Archives of Disease in Childhood. 1999 March; 80(3): 273-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10325711&dopt=Abstract

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In ovo tumorigenesis induced by avian osteopetrosis virus. Author(s): Franklin RM, Martin MT. Source: Virology. 1980 August; 105(1): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6251607&dopt=Abstract

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Increased urine heparan and chondroitin sulphate excretion in patients with osteopetrosis. Author(s): Steiner RD, Whyte MP, Chang E, Hanks J, Mattes C, Senephansiri H, Gibson KM. Source: Journal of Inherited Metabolic Disease. 2000 February; 23(1): 88-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10682314&dopt=Abstract

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Induction of bone resorption by parathyroid hormone in congenital malignant osteopetrosis. Author(s): Glorieux FH, Pettifor JM, Marie PJ, Delvin EE, Travers R, Shepard N. Source: Metab Bone Dis Relat Res. 1981; 3(2): 143-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6974819&dopt=Abstract

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Infantile osteopetrosis and neuronal storage disease. Author(s): Ambler MW, Trice J, Grauerholz J, O'Shea PA. Source: Neurology. 1983 April; 33(4): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6682191&dopt=Abstract

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Infantile osteopetrosis complicated by rickets. Author(s): Donnelly LF, Johnson JF 3rd, Benzing G. Source: Ajr. American Journal of Roentgenology. 1995 April; 164(4): 968-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726058&dopt=Abstract

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Infantile osteopetrosis complicating neuronal ceroid lipofuscinosis. Author(s): Takahashi K, Naito M, Yamamura F, Taki T, Sugino S, Taku K, Miike T. Source: Pathology, Research and Practice. 1990 December; 186(6): 697-706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2084635&dopt=Abstract

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Infantile osteopetrosis: a case report on dental findings. Author(s): Droz-Desprez D, Azou C, Bordigoni P, Bonnaure-Mallet M. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1992 October; 21(9): 422-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1432738&dopt=Abstract

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Infantile osteopetrosis: a case report with osteomyelitis of the maxilla. Author(s): Toranzo Fernandez JM, Noyola Frias MA, Hernandez Duarte SP. Source: J Clin Pediatr Dent. 2002 Fall; 27(1): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413177&dopt=Abstract

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Infantile osteopetrosis: report of two cases. Author(s): Young C, Lin KH, Chen RL, Chuu WM, Lin DT, Su IJ. Source: J Formos Med Assoc. 1992 January; 91(1): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1352341&dopt=Abstract

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Infantile osteopetrosis; bone marrow transplantation from a cousin donor. Author(s): Taylor GM, Dearden SP, Will AM, Evans DI, Stevens RF, Simon S, Super M, Morrell G, Fergusson WD, Brown IH. Source: Archives of Disease in Childhood. 1995 November; 73(5): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8554366&dopt=Abstract

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Intermediate form of osteopetrosis with recessive inheritance. Author(s): Kaibara N, Katsuki I, Hotokebuchi T, Takagishi K. Source: Skeletal Radiology. 1982; 9(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7157018&dopt=Abstract

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Intracranial calcification in children with osteopetrosis caused by carbonic anhydrase II deficiency. Author(s): Cumming WA, Ohlsson A. Source: Radiology. 1985 November; 157(2): 325-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2413500&dopt=Abstract

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Juvenile osteopetrosis: effects on blood and bone of prednisone and a low calcium, high phosphate diet. Author(s): Dorantes LM, Mejia AM, Dorantes S. Source: Archives of Disease in Childhood. 1986 July; 61(7): 666-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3740906&dopt=Abstract

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Kebab osteotomy of the tibia for a patient with osteopetrosis. Author(s): Nicholson P, Rice J, Quinlan W. Source: Injury. 1997 November-December; 28(9-10): 687-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624355&dopt=Abstract

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Lectin histochemistry of infantile lysosomal storage disease associated with osteopetrosis. Author(s): Alroy J, Castagnaro M, Skutelsky E, Lomakina I. Source: Acta Neuropathologica. 1994; 87(6): 594-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8091952&dopt=Abstract

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Lethal osteopetrosis with multiple fractures in utero. Author(s): el Khazen N, Faverly D, Vamos E, Van Regemorter N, Flament-Durand J, Carton B, Cremer-Perlmutter N. Source: American Journal of Medical Genetics. 1986 March; 23(3): 811-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3513575&dopt=Abstract

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Liver lysosomes in congenital osteopetrosis. A study of lysosomal function, calcitonin, parathyroid hormone, and 3',5'-adenosine monophosphate. Author(s): Rosen JF, Haymovits A. Source: The Journal of Pediatrics. 1972 September; 81(3): 518-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4340435&dopt=Abstract

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Localization of a gene for autosomal dominant osteopetrosis (Albers-Schonberg disease) to chromosome 1p21. Author(s): Van Hul W, Bollerslev J, Gram J, Van Hul E, Wuyts W, Benichou O, Vanhoenacker F, Willems PJ. Source: American Journal of Human Genetics. 1997 August; 61(2): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9311741&dopt=Abstract

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Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13. Author(s): Van Hul E, Gram J, Bollerslev J, Van Wesenbeeck L, Mathysen D, Andersen PE, Vanhoenacker F, Van Hul W. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 June; 17(6): 1111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054167&dopt=Abstract

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Localization of the mutation responsible for osteopetrosis in the op rat to a 1.5-cM genetic interval on rat chromosome 10: identification of positional candidate genes by radiation hybrid mapping. Author(s): Dobbins DE, Joe B, Hashiramoto A, Salstrom JL, Dracheva S, Ge L, Wilder RL, Remmers EF. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2002 October; 17(10): 1761-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369779&dopt=Abstract

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Locus heterogeneity of autosomal dominant osteopetrosis (ADO). Author(s): White KE, Koller DL, Takacs I, Buckwalter KA, Foroud T, Econs MJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 March; 84(3): 104751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084593&dopt=Abstract

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Longitudinal follow-up of malignant osteopetrosis by skeletal radiographs and restriction fragment length polymorphism analysis after bone marrow transplantation. Author(s): Schroeder RF, Johnson FL, Silberstein MJ, Neuman WL, Hoag JM, Farber RA, Noguchi A. Source: Pediatrics. 1992 December; 90(6): 986-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1359502&dopt=Abstract

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Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation. Author(s): Dini G, Floris R, Garaventa A, Oddone M, De Stefano F, De Marco R, Calcagno E, Faraci M, Claudiani F, Manfredini L, Dallorso S, Lanino E, Morreale G. Source: Bone Marrow Transplantation. 2000 July; 26(2): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918435&dopt=Abstract

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Long-term treatment of osteopetrosis with recombinant human interferon gamma. Author(s): Key LL Jr, Rodriguiz RM, Willi SM, Wright NM, Hatcher HC, Eyre DR, Cure JK, Griffin PP, Ries WL. Source: The New England Journal of Medicine. 1995 June 15; 332(24): 1594-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7753137&dopt=Abstract

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Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Author(s): Kornak U, Kasper D, Bosl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch TJ. Source: Cell. 2001 January 26; 104(2): 205-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207362&dopt=Abstract

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Macrophage colony-stimulating factor and receptor activator NF-kappaB ligand fail to rescue osteoclast-poor human malignant infantile osteopetrosis in vitro. Author(s): Flanagan AM, Massey HM, Wilson C, Vellodi A, Horton MA, Steward CG. Source: Bone. 2002 January; 30(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792569&dopt=Abstract

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Macrophage colony-stimulating factor: serum levels and cDNA structure in malignant osteopetrosis. Author(s): Naffakh N, Le Gall S, Danos O, Heard JM, Cournot G, Motoyoshi K, Vilmer E. Source: Blood. 1993 May 15; 81(10): 2817-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8490189&dopt=Abstract

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Major cerebral arterial and venous disease in osteopetrosis. Author(s): Makin GJ, Coates RK, Pelz D, Drake CG, Barnett HJ. Source: Stroke; a Journal of Cerebral Circulation. 1986 January-February; 17(1): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3945974&dopt=Abstract

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Malignant infantile osteopetrosis initially presenting with neonatal hypocalcemia: case report. Author(s): Chen CJ, Lee MY, Hsu ML, Lien SH, Cheng SN. Source: Annals of Hematology. 2003 January; 82(1): 64-7. Epub 2002 December 11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574970&dopt=Abstract

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Malignant infantile osteopetrosis presenting with neonatal hypocalcaemia. Author(s): Srinivasan M, Abinun M, Cant AJ, Tan K, Oakhill A, Steward CG. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2000 July; 83(1): F21-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873166&dopt=Abstract

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Malignant infantile osteopetrosis: otolaryngological complications and management. Author(s): Stocks RM, Wang WC, Thompson JW, Stocks MC 2nd, Horwitz EM. Source: Archives of Otolaryngology--Head & Neck Surgery. 1998 June; 124(6): 689-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639480&dopt=Abstract

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Malignant osteopetrosis and juvenile chronic myeloid leukemia. Author(s): Ozsoylu S. Source: Pediatric Hematology and Oncology. 1994 May-June; 11(3): 337-8, 345. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8060818&dopt=Abstract

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Malignant osteopetrosis in ancient Nubia. A case from the period 350-550 A.D. Author(s): Nielsen OV, Alexandersen V. Source: Dan Med Bull. 1971 October; 18(5): 125-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5116085&dopt=Abstract

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Malignant osteopetrosis manifested as juvenile chronic myeloid leukemia. Author(s): Toren A, Neumann Y, Meyer JJ, Mandel M, Schiby G, Kende G, Bassat I, Rechavi G. Source: Pediatric Hematology and Oncology. 1993 April-June; 10(2): 187-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8318376&dopt=Abstract

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Malignant osteopetrosis obscured by maternal vitamin D deficiency in a neonate. Author(s): Popp D, Zieger B, Schmitt-Graff A, Nutzenadel W, Schaefer F. Source: European Journal of Pediatrics. 2000 June; 159(6): 412-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867844&dopt=Abstract

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Malignant osteopetrosis treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Author(s): Kubo T, Tanaka H, Ono H, Moriwake T, Kanzaki S, Seino Y. Source: The Journal of Pediatrics. 1993 August; 123(2): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8345424&dopt=Abstract

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Malignant osteopetrosis with rickets. Author(s): Ozsoylu S. Source: European Journal of Pediatrics. 2001 February; 160(2): 137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271386&dopt=Abstract

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Malignant osteopetrosis: a disease of abnormal osteoclast proliferation. Author(s): Teitelbaum SL, Coccia PF, Brown DM, Kahn AJ. Source: Metab Bone Dis Relat Res. 1981; 3(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7289877&dopt=Abstract

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Malignant osteopetrosis: c-src kinase is not reduced in fibroblasts. Author(s): Meyerson G, Dahl N, Pahlman S. Source: Calcified Tissue International. 1993 July; 53(1): 69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7688650&dopt=Abstract

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Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation. Author(s): Rawlinson PS, Green RH, Coggins AM, Boyle IT, Gibson BE. Source: Archives of Disease in Childhood. 1991 May; 66(5): 638-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2039258&dopt=Abstract

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Malignant recessive osteopetrosis. Author(s): Phadke SR, Gupta A, Pahi J, Pandey A, Gautam P, Agarwal SS. Source: Indian Pediatrics. 1999 January; 36(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10709125&dopt=Abstract

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Managing osteopetrosis in children: a nutrition challenge. Author(s): Williams R, Wang W. Source: Journal of the American Dietetic Association. 1996 February; 96(2): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8557944&dopt=Abstract

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Manifestations of osteopetrosis. Author(s): Thompson RD, Hale ML, Montgomery JC, Montana-Villamizar E. Source: J Oral Surg. 1969 January; 27(1): 63-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5248080&dopt=Abstract

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Mapping of autosomal dominant osteopetrosis type II (Albers-Schonberg disease) to chromosome 16p13.3. Author(s): Benichou O, Cleiren E, Gram J, Bollerslev J, de Vernejoul MC, Van Hul W. Source: American Journal of Human Genetics. 2001 September; 69(3): 647-54. Epub 2001 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468688&dopt=Abstract

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Marble brain disease: recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families. Author(s): Ohlsson A, Stark G, Sakati N. Source: Developmental Medicine and Child Neurology. 1980 February; 22(1): 72-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7358236&dopt=Abstract

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Marble brain syndrome: osteopetrosis, renal acidosis and calcification of the brain. Author(s): Jacquemin C, Mullaney P, Svedberg E. Source: Neuroradiology. 1998 October; 40(10): 662-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9833897&dopt=Abstract

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Marrow transplantation for juvenile osteopetrosis. Author(s): Sorell M, Kapoor N, Kirkpatrick D, Rosen JF, Chaganti RS, Lopez C, Dupont B, Pollack MS, Terrin BN, Harris MB, Vine D, Rose JS, Goossen C, Lane J, Good RA, O'Reilly RJ. Source: The American Journal of Medicine. 1981 June; 70(6): 1280-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7015858&dopt=Abstract

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Maxillary osteomyelitis secondary to osteopetrosis. Author(s): Hanada T, Furuta S, Moriyama I, Hanamure Y, Miyanohara T, Ohyama M. Source: Rhinology. 1996 December; 34(4): 242-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9050105&dopt=Abstract

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Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers. Author(s): Waguespack SG, Hui SL, White KE, Buckwalter KA, Econs MJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 May; 87(5): 2212-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994366&dopt=Abstract

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Mechanisms of osteoclast dysfunction in human osteopetrosis: abnormal osteoclastogenesis and lack of osteoclast-specific adhesion structures. Author(s): Teti A, Migliaccio S, Taranta A, Bernardini S, De Rossi G, Luciani M, Iacobini M, De Felice L, Boldrini R, Bosman C, Corsi A, Bianco P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 December; 14(12): 2107-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10620070&dopt=Abstract

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Megadose methylprednisolone treatment for malignant osteopetrosis. Author(s): van Lie Peters EM, Aronson DC, Everts V, Dooren LJ. Source: European Journal of Pediatrics. 1994 October; 153(10): 779-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7813540&dopt=Abstract

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Microphthalmia-associated transcription factor (MITF) locus lacks linkage to human vitiligo or osteopetrosis: an evaluation. Author(s): Tripathi RK, Flanders DJ, Young TL, Oetting WS, Ramaiah A, King RA, Boissy RE, Nordlund JJ. Source: Pigment Cell Research / Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society. 1999 June; 12(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10385915&dopt=Abstract

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Middle cerebral arterial occlusion in a child with osteopetrosis major. Author(s): Tasdemir HA, Dagdemir A, Celenk C, Albayrak D. Source: European Radiology. 2001; 11(1): 145-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194907&dopt=Abstract

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Mild osteopetrosis in the microphthalmia-oak ridge mouse. A model for intermediate autosomal recessive osteopetrosis in humans. Author(s): Nii A, Steingrimsson E, Copeland NG, Jenkins NA, Ward JM. Source: American Journal of Pathology. 1995 December; 147(6): 1871-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7495310&dopt=Abstract

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Mineral metabolism in infants with malignant osteopetrosis: heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology. Author(s): Cournot G, Trubert-Thil CL, Petrovic M, Boyle A, Cormier C, Girault D, Fischer A, Garabedian M. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1992 January; 7(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1549952&dopt=Abstract

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Misleading radiology following bone marrow transplantation for infantile osteopetrosis. Author(s): O'Meara A, Breatnach F, Kelleher J. Source: European Journal of Pediatrics. 1990 March; 149(6): 447-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2332019&dopt=Abstract

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Mixed-sclerosing-bone-dystrophy (osteopathia striata and osteopetrosis) and Cushing's syndrome. Author(s): Proto G, Bertolissi F, Moretti C, Corsi M. Source: Bone. 1990; 11(3): 199-203. Erratum In: Bone 1990; 11(6): 453. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2390377&dopt=Abstract

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Mixed-sclerosing-bone-dystrophy (osteopathia striata and osteopetrosis) and Cushing's syndrome. Author(s): Spranger J. Source: Bone. 1991; 12(2): 133. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2064841&dopt=Abstract

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Mixed-sclerosing-bone-dystrophy: 42-year follow-up of a case reported as osteopetrosis. Author(s): Pacifici R, Murphy WA, Teitelbaum SL, Whyte MP. Source: Calcified Tissue International. 1986 March; 38(3): 175-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3085895&dopt=Abstract

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Morphologic features of bone in human osteopetrosis. Author(s): Helfrich MH, Aronson DC, Everts V, Mieremet RH, Gerritsen EJ, Eckhardt PG, Groot CG, Scherft JP. Source: Bone. 1991; 12(6): 411-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1797056&dopt=Abstract

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Multiple fractures in a 3-month-old infant with severe infantile osteopetrosis. Author(s): Bodamer OA, Bravermann RM, Craigen WJ. Source: Journal of Paediatrics and Child Health. 2001 October; 37(5): 520-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885723&dopt=Abstract

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Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat. Author(s): Dobbins DE, Sood R, Hashiramoto A, Hansen CT, Wilder RL, Remmers EF. Source: Biochemical and Biophysical Research Communications. 2002 June 28; 294(5): 1114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074592&dopt=Abstract

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Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Author(s): Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch TJ, Kubisch C. Source: Human Molecular Genetics. 2000 August 12; 9(13): 2059-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942435&dopt=Abstract

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Nature of osteopetrosis. Author(s): Little K. Source: British Medical Journal. 1969 April 5; 2(648): 49-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5776223&dopt=Abstract

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Neuroaxonal dystrohpy and osteopetrosis. Author(s): Fitch N, Carpenter S. Source: Annals of Neurology. 1978 July; 4(1): 91-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=697333&dopt=Abstract

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Neurological aspects of osteopetrosis. Author(s): Steward CG. Source: Neuropathology and Applied Neurobiology. 2003 April; 29(2): 87-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662317&dopt=Abstract

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Neurological complications of infantile osteopetrosis. Author(s): Lehman RA, Reeves JD, Wilson WB, Wesenberg RL. Source: Annals of Neurology. 1977 November; 2(5): 378-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=617576&dopt=Abstract

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Neurological complications of osteopetrosis. Author(s): Amacher AL. Source: Childs Brain. 1977; 3(5): 257-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=902509&dopt=Abstract

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Neutrophil defect associated with malignant infantile osteopetrosis. Author(s): Beard CJ, Key L, Newburger PE, Ezekowitz RA, Arceci R, Miller B, Proto P, Ryan T, Anast C, Simons ER. Source: The Journal of Laboratory and Clinical Medicine. 1986 November; 108(5): 498505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3021878&dopt=Abstract

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Nonbacterial thrombotic endocarditis and nondisseminated malignancy associated with osteopetrosis. Author(s): Sand JJ, Biller J, Aschenbrener CA. Source: European Neurology. 1987; 27(3): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3040417&dopt=Abstract

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Non-Hodgkin's lymphoma in a patient with osteopetrosis. Author(s): Shibuya H, Suzuki T, Matsubara S, Suzuki S. Source: Lymphology. 1986 June; 19(2): 90-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3736126&dopt=Abstract

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Non-immune hydrops fetalis due to osteopetrosis congenita. Author(s): Mathur BP, Karan S. Source: Indian Pediatrics. 1984 August; 21(8): 651-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6519793&dopt=Abstract

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Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis. Author(s): Michigami T, Kageyama T, Satomura K, Shima M, Yamaoka K, Nakayama M, Ozono K. Source: Bone. 2002 February; 30(2): 436-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856654&dopt=Abstract

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Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. Author(s): Scimeca JC, Quincey D, Parrinello H, Romatet D, Grosgeorge J, Gaudray P, Philip N, Fischer A, Carle GF. Source: Human Mutation. 2003 February; 21(2): 151-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552563&dopt=Abstract

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Nutrition in patients with osteopetrosis on interferon gamma. Author(s): Key LL Jr, Oexmann MJ, Green L. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1997 November-December; 13(11-12): 988-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9433718&dopt=Abstract

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Optic nerve decompression for osteopetrosis in early childhood. Author(s): Haines SJ, Erickson DL, Wirtschafter JD. Source: Neurosurgery. 1988 October; 23(4): 470-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3200377&dopt=Abstract

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Optic nerve decompression in osteopetrosis. Author(s): Al-Mefty O, Fox JL, Al-Rodhan N, Dew JH. Source: Journal of Neurosurgery. 1988 January; 68(1): 80-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3335915&dopt=Abstract

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Oral aspects of osteopetrosis. Author(s): Bjorvatn K, Gilhuus-Moe O, Aarskog D. Source: Scand J Dent Res. 1979 August; 87(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=295483&dopt=Abstract

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Orthopedic management of osteopetrosis: results of a survey and review of the literature. Author(s): Armstrong DG, Newfield JT, Gillespie R. Source: Journal of Pediatric Orthopedics. 1999 January-February; 19(1): 122-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9890301&dopt=Abstract

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Osteoarthritis associated with osteopetrosis treated by total hip replacement arthroplasty. Report of a case. Author(s): Janecki CJ, Nelson CL. Source: Cleve Clin Q. 1971 October; 38(4): 169-77. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5166044&dopt=Abstract

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Osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. Report of a case. Author(s): Casden AM, Jaffe FF, Kastenbaum DM, Bonar SF. Source: Clinical Orthopaedics and Related Research. 1989 October; (247): 202-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2791389&dopt=Abstract

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Osteoclast abnormalities in idiopathic osteopetrosis. Reference to the ultrastructural histochemistry study. Author(s): van Tran P, Dryll A, Lansaman J, Naveau B, Treve R, Miravet L, Ryckewaert A. Source: Virchows Arch a Pathol Anat Histopathol. 1985; 408(2-3): 269-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3936266&dopt=Abstract

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Osteoclast morphology in autosomal recessive malignant osteopetrosis due to a TCIRG1 gene mutation. Author(s): Bruder E, Stallmach T, Peier K, Superti-Furga A, Vezzoni P. Source: Pediatric Pathology & Molecular Medicine. 2003 January-February; 22(1): 3-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687885&dopt=Abstract

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Osteoclasts in human osteopetrosis contain viral-nucleocapsid-like nuclear inclusions. Author(s): Mills BG, Yabe H, Singer FR. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1988 February; 3(1): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3213601&dopt=Abstract

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Osteomyelitis complicating osteopetrosis--a case report. Author(s): Juggins KJ, Walton GM, Patel M. Source: Dent Update. 2001 December; 28(10): 509-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862853&dopt=Abstract

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Osteomyelitis of the mandible associated with osteopetrosis. Author(s): Steiner M, Gould AR, Means WR. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1983 June; 41(6): 395-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6574222&dopt=Abstract

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Osteomyelitis of the mandible associated with osteopetrosis: report of a case. Author(s): Lawoyin DO, Daramola JO, Ajagbe HA, Nyako EA, Lawoyin JO. Source: The British Journal of Oral & Maxillofacial Surgery. 1988 August; 26(4): 330-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3166967&dopt=Abstract

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Osteomyelitis of the mandible in a patient with malignant osteopetrosis. Author(s): Osborn R, Boland T, DeLuchi S, Beirne OR. Source: J Oral Med. 1985 April-June; 40(2): 76-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3858467&dopt=Abstract

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Osteomyelitis of the mandible in a patient with osteopetrosis. Author(s): Nitzan DW, Marmary Y. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1982 June; 40(6): 377-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6951979&dopt=Abstract

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Osteomyelitis of the mandible. An initial feature in late-onset osteopetrosis. Author(s): Shaff MI, Mathis JM. Source: Arch Otolaryngol. 1982 February; 108(2): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7059314&dopt=Abstract

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Osteomyelitis of the maxilla in a patient with osteopetrosis (Albers-Schonberg disease). Author(s): Crockett DM, Stanley RB, Lubka R. Source: Otolaryngology and Head and Neck Surgery. 1986 July; 95(1): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3106886&dopt=Abstract

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Osteomyelitis of the maxilla secondary to osteopetrosis: report of a case. Author(s): Barry CP, Ryan CD. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2003 January; 95(1): 12-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539021&dopt=Abstract

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Osteomyelitis secondary to osteopetrosis: report of case. Author(s): Bok P, van der Waal I. Source: J Oral Surg. 1974 October; 32(10): 769-72. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4528665&dopt=Abstract

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Osteopathia striata, osteopetrosis, and impaired hearing. A case report. Author(s): Jones MD, Mulcahy ND. Source: Arch Otolaryngol. 1968 February; 87(2): 116-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5635349&dopt=Abstract

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Osteopetrosis (Albers Schoenberg disease, osteosclerosis fragilis generalisata, osteoscleroisis congenital diffusa). A case report with review of the literature. Author(s): Mopkar YR. Source: Indian Journal of Medical Sciences. 1968 May; 22(5): 307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5678433&dopt=Abstract

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Osteopetrosis (Albers Schonberg's Disease). Author(s): Gupta SP, Tewari GN, Gupta RC. Source: Indian J Pediatr. 1969 December; 36(263): 478-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5384111&dopt=Abstract

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Osteopetrosis (Albers-Schonberg): appearance on three-phase bone scintigraphy. Author(s): Roitberg D, Vitti RA, Maslack MM. Source: Clinical Nuclear Medicine. 1997 December; 22(12): 858-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9408655&dopt=Abstract

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Osteopetrosis (Albers-Schonberg's Disease). Report of three cases in one sibship. Author(s): Anand JS. Source: Indian J Pediatr. 1966 June; 33(221): 177-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5963198&dopt=Abstract

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Osteopetrosis (Marble bone disease) of the temporal bone. Author(s): Hamersma H. Source: The Laryngoscope. 1970 October; 80(10): 1518-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4991443&dopt=Abstract

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Osteopetrosis ('marble bone' disease). Author(s): Manusov EG, Douville DR, Page LV, Trivedi DV. Source: American Family Physician. 1993 January; 47(1): 175-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8418580&dopt=Abstract

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Osteopetrosis (marble bone disease)--agenesis of paranasal sinuses. Author(s): Paulose KO, Al Khalifa S, Shenoy PK, Harris S, Sharma RK. Source: The Journal of Laryngology and Otology. 1988 November; 102(11): 1047-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3209943&dopt=Abstract

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Osteopetrosis and Glanzmann's thrombasthenia in a child. Author(s): Yarali N, Fisgin T, Duru F, Kara A. Source: Annals of Hematology. 2003 April; 82(4): 254-6. Epub 2003 March 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707732&dopt=Abstract

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Osteopetrosis and mandibular osteitis in adult. Report of a case in Guadeloupe. Author(s): Billy-Brissac R, Foucan L, Roudier M, Trival M. Source: Rev Rhum Engl Ed. 1995 April; 62(4): 303-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7606428&dopt=Abstract

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Osteopetrosis and osteoporosis: two sides of the same coin. Author(s): Lazner F, Gowen M, Pavasovic D, Kola I. Source: Human Molecular Genetics. 1999; 8(10): 1839-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469835&dopt=Abstract

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Osteopetrosis and rickets: an intriguing association. Author(s): Oliveira G, Boechat MI, Amaral SM, Young LW. Source: Am J Dis Child. 1986 April; 140(4): 377-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3953529&dopt=Abstract

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Osteopetrosis and total hip arthroplasty. Report of two cases. Author(s): Matsuno T, Katayama N. Source: International Orthopaedics. 1997; 21(6): 409-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498153&dopt=Abstract

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Osteopetrosis appearance on bone scan. Author(s): Dumont M, Lamoureux J, Lamoureux F, Danais S, Soucy JP, Taillefer R. Source: Clinical Nuclear Medicine. 1983 September; 8(9): 446. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6227443&dopt=Abstract

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Osteopetrosis as a model for studying bone resorption. Author(s): Benichou OD, Benichou B, de Vernejoul MC. Source: Rev Rhum Engl Ed. 1998 December; 65(12): 778-87. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9923047&dopt=Abstract

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Osteopetrosis associated with familial paraplegia: report of a family. Author(s): Jacques S, Garner JR, Johnson D, Shelden CH. Source: Paraplegia. 1975 November; 13(3): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1208112&dopt=Abstract

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Osteopetrosis associated with proximal and distal tubular acidosis. Author(s): Vainsel M, Fondu P, Cadranel S, Rocmans C, Gepts W. Source: Acta Paediatr Scand. 1972 July; 61(4): 429-34. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5041390&dopt=Abstract

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Osteopetrosis complicated by osteomyelitis of the mandible: a case report including gross and microscopic findings. Author(s): Barbaglio A, Cortelazzi R, Martignoni G, Nocini PF. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1998 March; 56(3): 393-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9496856&dopt=Abstract

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Osteopetrosis fetalis. Report on a case, with special reference to ultrastructure. Author(s): Bonucci E, Sartori E, Spina M. Source: Virchows Arch a Pathol Anat Histol. 1975 October 20; 368(2): 109-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=810948&dopt=Abstract

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Osteopetrosis fragilis (Albers-Schonberg's disease) (Case report). Author(s): el-Kahky M. Source: J Egypt Med Assoc. 1969; 52(7): 582-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5365921&dopt=Abstract

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Osteopetrosis from the ophthalmological point of view. A report of two cases. Author(s): Aasved H. Source: Acta Ophthalmol (Copenh). 1970; 48(4): 771-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5536725&dopt=Abstract

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Osteopetrosis in a Nigerian woman--a case report. Author(s): Durosinmi MA, Lawoyin DO, Ogunseyinde AO, Avoseh MA, Williams CK, Daramola JO. Source: Afr J Med Med Sci. 1987 September; 16(3): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2829607&dopt=Abstract

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Osteopetrosis in an infant. Author(s): Kumar D, Agrawal PK. Source: J Indian Med Assoc. 1990 March; 88(3): 84-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2262689&dopt=Abstract

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Osteopetrosis in children. Author(s): al-Rasheed SA, al-Mohrij O, al-Jurayyan N, al-Herbish A, al-Mugeiren M, alSalloum A, al-Hussain M, el-Desouki M. Source: Int J Clin Pract. 1998 January-February; 52(1): 15-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9536561&dopt=Abstract

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Osteopetrosis in children: a report of 26 cases. Author(s): Loria-Cortes R, Quesada-Calvo E, Cordero-Chaverri C. Source: The Journal of Pediatrics. 1977 July; 91(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=874663&dopt=Abstract

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Osteopetrosis in infancy. Author(s): Delidzakova M, Nikolova T, Grivceva N, Gordova A, Dzarlieva R, Kocova M. Source: God Zb Med Fak Skopje. 1977; 23: 893-901. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=615058&dopt=Abstract

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Osteopetrosis in Saudi children: a report of 10 cases. Author(s): Mahdi AH. Source: Annals of Tropical Paediatrics. 1988 June; 8(2): 112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2456727&dopt=Abstract

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Osteopetrosis in South Africa. The benign, lethal and intermediate forms. Author(s): Beighton P, Hamersma H, Cremin BJ. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1979 April 21; 55(17): 659-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=462288&dopt=Abstract

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Osteopetrosis in trauma. Author(s): Fish RM. Source: The Journal of Emergency Medicine. 1983; 1(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6680127&dopt=Abstract

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Osteopetrosis in two brothers with severe mental retardation. Author(s): Funderburk SJ. Source: Birth Defects Orig Artic Ser. 1975; 11(6): 91-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1201358&dopt=Abstract

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Osteopetrosis of the maxilla. Author(s): Long RG, Ziccardi VB. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 February; 91(2): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174587&dopt=Abstract

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Osteopetrosis of the temporal bone. Author(s): Hawke M, Jahn AF, Bailey D. Source: Arch Otolaryngol. 1981 May; 107(5): 278-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7224945&dopt=Abstract

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Osteopetrosis presenting with paroxysmal trigeminal neuralgia. A case report. Author(s): Chindia ML, Ocholla TJ, Imalingat B. Source: International Journal of Oral and Maxillofacial Surgery. 1991 August; 20(4): 199200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1940495&dopt=Abstract

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Osteopetrosis reconsidered as a curable immune disorder. Author(s): Milhaud G, Labat ML. Source: Biomedicine. 1979 June; 30(2): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=383170&dopt=Abstract

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Osteopetrosis reports of four cases. Author(s): Kumar VV, Raju PA, Rao IV. Source: Indian Pediatrics. 1989 September; 26(9): 938-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2634012&dopt=Abstract

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Osteopetrosis tarda (a case report). Author(s): Datta T, Basu J. Source: Indian Pediatrics. 1977 April; 14(4): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=924644&dopt=Abstract

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Osteopetrosis tarda--a case report. Author(s): Sharma A, Kumar S. Source: J Indian Med Assoc. 1999 January; 97(1): 22, 24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10549183&dopt=Abstract

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Osteopetrosis with arteritis: Case report and review of the literature. Author(s): Foca FJ, Liebeskind AL. Source: Archives of Physical Medicine and Rehabilitation. 1973 August; 54(8): 370-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4722013&dopt=Abstract

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Osteopetrosis with bilateral facial nerve palsy. Author(s): Bajaj S, Gupta SC, Nigam DK. Source: J Assoc Physicians India. 1986 July; 34(7): 529-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3759889&dopt=Abstract

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Osteopetrosis with calcifying tendinitis. Author(s): Quinn SF, Dyer R. Source: Southern Medical Journal. 1984 March; 77(3): 400-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6701629&dopt=Abstract

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Osteopetrosis with combined proximal and distal renal tubular acidosis. Author(s): Bregman H, Brown J, Rogers A, Bourke E. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1982 November; 2(3): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7148827&dopt=Abstract

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Osteopetrosis with precocious manifestations. (Report of 3 familial and 1 sporadic case). Author(s): Kozlowski K, Szmigiel C, Konik R, Ostrowski A, Walecki J. Source: Australasian Radiology. 1972 September; 16(3): 311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4658458&dopt=Abstract

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Osteopetrosis with rickets in infancy. Author(s): Ozdirim E, Altay C, Pirnar T. Source: Turk J Pediatr. 1981 July-September; 23(3): 211-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7345697&dopt=Abstract

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Osteopetrosis with rickets: report of two cases. Author(s): Sundaravalli N, Ranganathan G, Shetty MV, Raju VB. Source: Indian Pediatrics. 1975 August; 12(8): 715-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1205577&dopt=Abstract

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Osteopetrosis with spondylolysis--four cases in one family. Author(s): Saha MM, Bhardwaj OP, Srivastava G, Pramanick A, Gupta A. Source: The British Journal of Radiology. 1970 October; 43(514): 738-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5470424&dopt=Abstract

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Osteopetrosis-(Albers-Schonberg's disease). Author(s): Bhandari NR, Inamdar S, Jungalwala BN, Hussain S. Source: Indian Pediatrics. 1968 September; 5(9): 417-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5703830&dopt=Abstract

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Osteopetrosis, femoral fracture, and chronic osteomyelitis caused by Staphylococcus aureus small colony variants (SCV) treated by girdlestone resection--6-year follow-up. Author(s): Rolauffs B, Bernhardt TM, von Eiff C, Hart ML, Bettin D. Source: Archives of Orthopaedic and Trauma Surgery. 2002 December; 122(9-10): 547-50. Epub 2002 October 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483342&dopt=Abstract

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Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother. Author(s): Dupuis-Girod S, Corradini N, Hadj-Rabia S, Fournet JC, Faivre L, Le Deist F, Durand P, Doffinger R, Smahi A, Israel A, Courtois G, Brousse N, Blanche S, Munnich A, Fischer A, Casanova JL, Bodemer C. Source: Pediatrics. 2002 June; 109(6): E97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042591&dopt=Abstract

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Osteopetrosis, renal tubular acidosis and basal ganglia calcification in three sisters. Author(s): Whyte MP, Murphy WA, Fallon MD, Sly WS, Teitelbaum SL, McAlister WH, Avioli LV. Source: The American Journal of Medicine. 1980 July; 69(1): 64-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7386510&dopt=Abstract

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Osteopetrosis, renal tubular acidosis without urinary concentration abnormality, cerebral calcification and severe mental retardation in three Turkish brothers. Author(s): Ocal G, Berberoglu M, Adiyaman P, Cetinkaya E, Ekim M, Aycan Z, Evliyaoglu O. Source: J Pediatr Endocrinol Metab. 2001 November-December; 14(9): 1671-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795660&dopt=Abstract

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Osteopetrosis. Author(s): Kocher MS, Kasser JR. Source: Am J Orthop. 2003 May; 32(5): 222-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772872&dopt=Abstract

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Osteopetrosis. Author(s): Stoker DJ. Source: Seminars in Musculoskeletal Radiology. 2002 December; 6(4): 299-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541186&dopt=Abstract

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Osteopetrosis. Author(s): Carolino J, Perez JA, Popa A. Source: American Family Physician. 1998 March 15; 57(6): 1293-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9531912&dopt=Abstract

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Osteopetrosis. Author(s): Singer FR, Chang SS. Source: Semin Nephrol. 1992 March; 12(2): 191-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1561496&dopt=Abstract

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Osteopetrosis. Author(s): Verma DN, Rao VR, Gupta SK, Sasibabu K. Source: J Indian Med Assoc. 1978 January 1; 70(1): 14-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=670735&dopt=Abstract

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Osteopetrosis. Author(s): Ramavat LG, Ramavat S. Source: Indian Pediatrics. 1976 October; 13(10): 803-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1002244&dopt=Abstract

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Osteopetrosis. Author(s): Sengupta D, Mitra M. Source: J Indian Med Assoc. 1975 January 1; 64(1): 10-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1133457&dopt=Abstract

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Osteopetrosis. Author(s): Newman CL. Source: Proc R Soc Med. 1972 August; 65(8): 729-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5085970&dopt=Abstract

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Osteopetrosis. Author(s): Yu JS, Oates RK, Walsh KH, Stuckey SJ. Source: Archives of Disease in Childhood. 1971 June; 46(247): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5090659&dopt=Abstract

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Osteopetrosis. Author(s): Utley PM. Source: J Tenn Med Assoc. 1970 August; 63(8): 659-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5434028&dopt=Abstract

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Osteopetrosis. Author(s): Robichon J, Wiley JJ, Germain JP. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 1968 October; 11(4): 424-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5683600&dopt=Abstract

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Osteopetrosis. Author(s): Andreas A, Maniammal, Thilak G. Source: J Assoc Physicians India. 1985 July; 33(7): 490-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4055671&dopt=Abstract

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Osteopetrosis. A case report. Author(s): Wolf EW, Fernandez L. Source: Journal of the American Podiatric Medical Association. 1994 October; 84(10): 518-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7965685&dopt=Abstract

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Osteopetrosis. A clinical, genetic, metabolic, and morphologic study of the dominantly inherited, benign form. Author(s): Johnston CC Jr, Lavy N, Lord T, Vellios F, Merritt AD, Deiss WP Jr. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 1968 March; 47(2): 149-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4871758&dopt=Abstract

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Osteopetrosis. A genetic and epidemiological study. Author(s): Bollerslev J. Source: Clinical Genetics. 1987 February; 31(2): 86-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3829443&dopt=Abstract

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Osteopetrosis. A morphological study of twenty-one cases. Author(s): Milgram JW, Jasty M. Source: The Journal of Bone and Joint Surgery. American Volume. 1982 July; 64(6): 91229. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7085720&dopt=Abstract

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Osteopetrosis. A report of four cases. Author(s): Abdulsalam M, Wahidiyat I, Karyomanggolo WT, Tamaela LA. Source: Paediatr Indones. 1984 September-October; 24(9-10): 211-24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6545917&dopt=Abstract

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Osteopetrosis. Current clinical considerations. Author(s): Shapiro F. Source: Clinical Orthopaedics and Related Research. 1993 September; (294): 34-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358940&dopt=Abstract

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Osteopetrosis. The pharmaco-physiologic basis of therapy. Author(s): Key LL Jr, Ries WL. Source: Clinical Orthopaedics and Related Research. 1993 September; (294): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358949&dopt=Abstract

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Osteopetrosis: a case report including gross and microscopic findings in the mandible at autopsy. Author(s): Younai F, Eisenbud L, Sciubba JJ. Source: Oral Surg Oral Med Oral Pathol. 1988 February; 65(2): 214-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3278267&dopt=Abstract

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Osteopetrosis: a potential mimic of osteomyelitis on three-phase bone scintigraphy. Author(s): Ahmed Al-Kandari F, Abdulla Kazem N, David Collier B, Shah Syed GM. Source: Clinical Nuclear Medicine. 2003 January; 28(1): 54-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493966&dopt=Abstract

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Osteopetrosis: a review of the literature and report of a case complicated by osteomyelitis of the mandible. Author(s): Bakeman RJ, Abdelsayed RA, Sutley SH, Newhouse RF. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1998 October; 56(10): 1209-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9766551&dopt=Abstract

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Osteopetrosis: a scanning electron microscopic study. Author(s): Kuo TT, Davis CP. Source: Human Pathology. 1981 April; 12(4): 376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7239505&dopt=Abstract

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Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis. Author(s): Kapelushnik J, Shalev C, Yaniv I, Aker M, Carmi R, Cohen Z, Mozer A, Schulman C, Stein G, Or R. Source: Bone Marrow Transplantation. 2001 January; 27(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281380&dopt=Abstract

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Osteopetrosis: an interpretation of its pathogenesis. Author(s): Krook L, Whalen JP, Dorfman HD, Norman A, Nunez EA. Source: Skeletal Radiology. 1981; 7(3): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7330675&dopt=Abstract

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Osteopetrosis: an unusual case of terminal-tuft erosion. Author(s): Moss AA, Mainzer F. Source: Radiology. 1970 December; 97(3): 631-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5491753&dopt=Abstract

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Osteopetrosis: brain ultrasound and computed tomography findings. Author(s): Patel PJ, Kolawole TM, al-Mofada S, Malabarey TM, Hulailah A. Source: European Journal of Pediatrics. 1992 November; 151(11): 827-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1468457&dopt=Abstract

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Osteopetrosis: further heterogeneity. Author(s): Horton WA, Schimke RN, Iyama T. Source: The Journal of Pediatrics. 1980 October; 97(4): 580-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7420221&dopt=Abstract

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Osteopetrosis: MR characteristics at 1.5 T. Author(s): Rao VM, Dalinka MK, Mitchell DG, Spritzer CE, Kaplan F, August CS, Axel L, Kressel HY. Source: Radiology. 1986 October; 161(1): 217-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3763870&dopt=Abstract

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Osteopetrosis: nuclear medicine pathophysiologic correlation. Author(s): Palestro CJ, Fineman D, Solomon RW, Kim CK, Goldsmith SJ. Source: Clinical Nuclear Medicine. 1989 November; 14(11): 854-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2513159&dopt=Abstract

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Osteopetrosis: report of a case and discussion of the differential diagnosis. Author(s): Ruprecht A, Wagner H, Engel H. Source: Oral Surg Oral Med Oral Pathol. 1988 December; 66(6): 674-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3060776&dopt=Abstract

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Osteopetrosis: report of a case. Author(s): Cangiano R, Mooney J, Stratigos GT. Source: J Oral Surg. 1972 March; 30(3): 217-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4501101&dopt=Abstract

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Osteopetrosis: report of case. Author(s): Boyko A, Smylski PT. Source: J Oral Surg. 1974 November; 32(11): 859-63. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4530078&dopt=Abstract

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Osteopetrosis: some unusual radiological features with a short review. Author(s): Kolawole TM, Hawass ND, Patel PJ, Mahdi AH. Source: European Journal of Radiology. 1988 May; 8(2): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3383862&dopt=Abstract

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Osteopetrosis--improvement of hematologic findings with age. Author(s): Totan M, Albayrak D. Source: Indian J Pediatr. 1999 September-October; 66(5): 809-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798143&dopt=Abstract

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Osteopetrosis--multiple pathways for the interception of osteoclast function. Author(s): Marks SC Jr. Source: Appl Pathol. 1987; 5(3): 172-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3304355&dopt=Abstract

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Osteopetrosis--prosthodontic treatment. Author(s): Woodward JD, Smith JR, Beck HO. Source: The Journal of Prosthetic Dentistry. 1976 June; 35(6): 608-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=784952&dopt=Abstract

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Osteosclerosis versus osteopetrosis of the newborn. Author(s): Ozsoylu S, Besim A. Source: The Journal of Pediatrics. 1992 June; 120(6): 1005-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1593342&dopt=Abstract

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Otolaryngological complications of osteopetrosis. Author(s): Srirompotong S, Saeng-Sa-Ard S, Srirompotong S. Source: J Med Assoc Thai. 2002 April; 85(4): 514-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118501&dopt=Abstract

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Paget's disease with benign osteopetrosis and Crohn's disease. Author(s): Henderson RG, Long PJ, Al-Nafussi AI, Coombs RR, Gibson RN. Source: Journal of the Royal Society of Medicine. 1985 September; 78(9): 766-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3930726&dopt=Abstract

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Pathogenesis and treatment of infantile osteopetrosis. Author(s): Pojda Z. Source: Mater Med Pol. 1986 January-March; 18(1): 40-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3528688&dopt=Abstract

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Pathogenesis of osteosclerosis in autosomal dominant osteopetrosis. Author(s): Kovanlikaya A, Loro ML, Gilsanz V. Source: Ajr. American Journal of Roentgenology. 1997 April; 168(4): 929-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9124142&dopt=Abstract

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Patients with malignant osteopetrosis are at high risk of anesthetic morbidity and mortality. Author(s): Burt N, Haynes GR, Bailey MK. Source: Anesthesia and Analgesia. 1999 June; 88(6): 1292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10357332&dopt=Abstract

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Periodontal manifestations of osteopetrosis. Author(s): Trapnell DH. Source: The British Journal of Radiology. 1968 September; 41(489): 669-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5676052&dopt=Abstract

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Peripheral T-cell lymphoma in a patient with osteopetrosis. Author(s): Hashino S, Hirota G, Hasegawa M, Chiba K, Toyoshima N, Suzuki S, Kurosawa M, Musashi M, Asaka M. Source: Annals of Hematology. 2001 June; 80(6): 376-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475155&dopt=Abstract

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Petrous carotid canal stenosis in malignant osteopetrosis: CT documentation with MR angiographic correlation. Author(s): Cure JK, Key LL, Shankar L, Gross AJ. Source: Radiology. 1996 May; 199(2): 415-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8668787&dopt=Abstract

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Physiologic osteosclerosis versus osteopetrosis of the newborn. Author(s): Nadvi SZ, Kottamasu SR, Bawle E, Abella E. Source: Clinical Pediatrics. 1999 April; 38(4): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326179&dopt=Abstract

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Plasma calcitonin activity in a patient with thyroid medullary carcinoma and her children with osteopetrosis. Author(s): Verdy M, Beaulieu R, Demers L. Source: The Journal of Clinical Endocrinology and Metabolism. 1971 February; 32(2): 216-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5539034&dopt=Abstract

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Portal hypertension in a patient with osteopetrosis. A case report with discussion of the mechanism of portal hypertension. Author(s): Denison EK, Peters RL, Reynolds TB. Source: Archives of Internal Medicine. 1971 August; 128(2): 279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5564207&dopt=Abstract

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Posterior spinal instrumentation and fusion of a neuromuscular scoliosis in a patient with autosomal dominant osteopetrosis. Author(s): Westerlund LE, Blanco JS, Chhabra A. Source: Spine. 2000 January 15; 25(2): 265-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685493&dopt=Abstract

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Prenatal axonal dystrophy and osteopetrosis. Author(s): Fitch N, Carpenter S, Lachance RC. Source: Arch Pathol. 1973 May; 95(5): 298-301. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4735089&dopt=Abstract

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Prenatal diagnosis of autosomal recessive osteopetrosis, infantile type, by X-ray evaluation. Author(s): Ogur G, Ogur E, Celasun B, Baser I, Imirzalioglu N, Ozturk T, Alemdaroglu A. Source: Prenatal Diagnosis. 1995 May; 15(5): 477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7644439&dopt=Abstract

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Prenatal diagnosis of malignant osteopetrosis in Bedouin families by linkage analysis. Author(s): Shalev H, Mishori-Dery A, Kapelushnik J, Moser A, Sheffield VC, McClain A, Carmi R. Source: Prenatal Diagnosis. 2001 March; 21(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260604&dopt=Abstract

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Primary optic atrophy and autosomal dominant osteopetrosis type II. Author(s): Singh SK, Singh R, Maurya VK. Source: J Assoc Physicians India. 2002 June; 50: 850. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12240863&dopt=Abstract

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Proceedings: Dik Kop disease: a variety of osteopetrosis. Author(s): Beighton P. Source: The Journal of Bone and Joint Surgery. British Volume. 1975 May; 57(2): 260. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1141355&dopt=Abstract

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Pseudo-avascular necrosis of the hips in a sporadic case of osteopetrosis. Author(s): Manolios N, Wiseman J, Webb J. Source: Clinical Rheumatology. 1987 September; 6(3): 408-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3442965&dopt=Abstract

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Pycnodysostosis of Maroteaux and Lamy. Osteopetrosis acro-osteolytica. Author(s): Bertrand P, Marchal G, Igodt-Ameye L, Vanderschueren-Lodeweyckx M. Source: Acta Paediatr Belg. 1977 January-March; 30 Suppl 1: 1-18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=868507&dopt=Abstract

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Quantification of bone mineralization by dual photon absorptiometry in osteopetrosis. Author(s): Fig LM, Shulkin BL. Source: Clinical Nuclear Medicine. 1989 July; 14(7): 544-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2766640&dopt=Abstract

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Radiographic type I autosomal dominant osteopetrosis with syringohydromyelia. Author(s): Sari A, Demirci A. Source: Neuroradiology. 1996 August; 38(6): 532-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8880712&dopt=Abstract

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Radiologic manifestations of osteopetrosis. Author(s): Xu Y, Xu S, Zhan J, Huang X, Feng G, Wang B, Chen W. Source: Chin Med J (Engl). 1995 September; 108(9): 692-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8575237&dopt=Abstract

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Radiological case of the month. Autosomal recessive osteopetrosis. Author(s): Yavuz H, Caliskan O, Bozkir A, Arslan A, Koc H, Wood BP. Source: Am J Dis Child. 1992 November; 146(11): 1309-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415067&dopt=Abstract

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Radiological case of the month. Osteopetrosis (Albers-Schomberg's disease) with osteomyelitis. Author(s): Gwinn JL, Lee FA. Source: Am J Dis Child. 1972 July; 124(1): 91-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5033756&dopt=Abstract

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Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. Author(s): Bollerslev J, Andersen PE Jr. Source: Bone. 1988; 9(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3377922&dopt=Abstract

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Recent developments in the understanding of the pathophysiology of osteopetrosis. Author(s): Felix R, Hofstetter W, Cecchini MG. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1996 February; 134(2): 143-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8630510&dopt=Abstract

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Recombinant human interferon gamma therapy for osteopetrosis. Author(s): Key LL Jr, Ries WL, Rodriguiz RM, Hatcher HC. Source: The Journal of Pediatrics. 1992 July; 121(1): 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1320672&dopt=Abstract

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Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report. Author(s): Fischer A, Friedrich W, Fasth A, Blanche S, Le Deist F, Girault D, Veber F, Vossen J, Lopez M, Griscelli C, et al. Source: Blood. 1991 January 15; 77(2): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1985691&dopt=Abstract

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Renal tubular acidosis and osteopetrosis in siblings. Author(s): Bourke E, Delaney VB, Mosawi M, Reavey P, Weston M. Source: Nephron. 1981; 28(6): 268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7312081&dopt=Abstract

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Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency. Author(s): Repetto HA. Source: Pediatric Nephrology (Berlin, Germany). 1998 April; 12(3): 261. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9630052&dopt=Abstract

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Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification. Author(s): Nagai R, Kooh SW, Balfe JW, Fenton T, Halperin ML. Source: Pediatric Nephrology (Berlin, Germany). 1997 October; 11(5): 633-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323296&dopt=Abstract

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Renal tubular acidosis and osteopetrosis. Author(s): Donckerwolcke R, Stone P. Source: Pediatric Nephrology (Berlin, Germany). 1999 February; 13(2): 180. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229010&dopt=Abstract

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Retinal atrophy in osteopetrosis. Author(s): Keith CG. Source: Archives of Ophthalmology. 1968 March; 79(3): 234-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4170880&dopt=Abstract

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Retroviral expression in mononuclear blood cells isolated from a patient with osteopetrosis (Albers-Schonberg disease). Author(s): Labat ML, Bringuier AF, Chandra A, Einhorn TA, Chandra P. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1990 May; 5(5): 425-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1695060&dopt=Abstract

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Retroviruses, immunosuppression and osteopetrosis. Author(s): Labat ML. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1986; 40(3): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3017470&dopt=Abstract

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Reversal of obstructive sleep apnea in osteopetrosis following bone marrow transplantation. Author(s): Stocks R, Cannon CB, Wang WC, Horwitz EM, Thompson JW. Source: Clinical Pediatrics. 2002 January-February; 41(1): 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866369&dopt=Abstract

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Reversal of optic canal stenosis in osteopetrosis after bone marrow transplant. Author(s): Kerr NC, Wang WC, Mohadjer Y, Haik BG, Kaste SC, Horwitz EM. Source: American Journal of Ophthalmology. 2000 September; 130(3): 370-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11020426&dopt=Abstract

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Rickets in osteopetrosis--a paradoxical association. Author(s): Kulkarni ML, Matadh PS. Source: Indian Pediatrics. 2003 June; 40(6): 561-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824667&dopt=Abstract

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Rickets, osteomalacia, and osteopetrosis. Author(s): Balsan S, Garabedian M. Source: Current Opinion in Rheumatology. 1991 June; 3(3): 496-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1883705&dopt=Abstract

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Scintigraphic detection of osteomyelitis in osteopetrosis. Author(s): Puskas C, Sciuk J. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1994 January; 35(1): 95-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8271069&dopt=Abstract

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Scintigraphy in a patient with complicated osteopetrosis. Author(s): Adams BK. Source: Clinical Nuclear Medicine. 1989 May; 14(5): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2656038&dopt=Abstract

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Serum creatine kinase isoenzyme BB in mammalian osteopetrosis. Author(s): Bollerslev J, Ueland T, Landaas S, Marks SC Jr. Source: Clinical Orthopaedics and Related Research. 2000 August; (377): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943208&dopt=Abstract

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Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types. Author(s): Bollerslev J, Nielsen HK, Storm T, Mosekilde L. Source: Bone. 1988; 9(6): 355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3248198&dopt=Abstract

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Severe obstructive sleep apnea in a child with osteopetrosis. Author(s): Carter M, Stokes D, Wang W. Source: Clinical Pediatrics. 1988 February; 27(2): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3338229&dopt=Abstract

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Skeletal and reticuloendothelial imaging in osteopetrosis: case report. Author(s): Park HM, Lambertus J. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1977 November; 18(11): 1091-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=915085&dopt=Abstract

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Slipped capital femoral epiphysis in a patient with type II autosomal dominant osteopetrosis. Author(s): Cooper JR, Sprigg A. Source: Skeletal Radiology. 1998 September; 27(9): 515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809882&dopt=Abstract

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Slipped capital femoral epiphysis in osteopetrosis: an unusual case. Author(s): Kinik H, Polat O, Yildiz Y, Mergen E. Source: Archives of Orthopaedic and Trauma Surgery. 2002 June; 122(5): 302-5. Epub 2002 February 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070653&dopt=Abstract

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Splenectomy in the management of the anemia and thrombocytopenia of osteopetrosis (marble bone disease). Author(s): Besselman DM. Source: The Journal of Pediatrics. 1966 September; 69(3): 455-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5946454&dopt=Abstract

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Spondylolysis in children who have osteopetrosis. Author(s): Martin RP, Deane RH, Collett V. Source: The Journal of Bone and Joint Surgery. American Volume. 1997 November; 79(11): 1685-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384428&dopt=Abstract

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Spondylolysis in osteopetrosis. Author(s): Szappanos L, Szepesi K, Thomazy V. Source: The Journal of Bone and Joint Surgery. British Volume. 1988 May; 70(3): 428-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3372566&dopt=Abstract

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Stress fracture of the vertebral arch in osteopetrosis. Author(s): Suzuki S, Awaya G. Source: Clinical Orthopaedics and Related Research. 1986 December; (213): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3780097&dopt=Abstract

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Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types. Author(s): Bollerslev J, Steiniche T, Melsen F, Mosekilde L. Source: Bone. 1989; 10(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2660883&dopt=Abstract

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Study of the nonresorptive phenotype of osteoclast-like cells from patients with malignant osteopetrosis: a new approach to investigating pathogenesis. Author(s): Flanagan AM, Sarma U, Steward CG, Vellodi A, Horton MA. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2000 February; 15(2): 352-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10703938&dopt=Abstract

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Successful bone-marrow transplantation for infantile malignant osteopetrosis. Author(s): Coccia PF, Krivit W, Cervenka J, Clawson C, Kersey JH, Kim TH, Nesbit ME, Ramsay NK, Warkentin PI, Teitelbaum SL, Kahn AJ, Brown DM. Source: The New England Journal of Medicine. 1980 March 27; 302(13): 701-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6986555&dopt=Abstract

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Successful treatment of infantile malignant osteopetrosis by bone-marrow transplantation. A case report. Author(s): Kaplan FS, August CS, Fallon MD, Dalinka M, Axel L, Haddad JG. Source: The Journal of Bone and Joint Surgery. American Volume. 1988 April; 70(4): 61723. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3281954&dopt=Abstract

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Superoxide generation in transformed B-lymphocytes from patients with severe, malignant osteopetrosis. Author(s): Yang S, Ries WL, Key LL Jr. Source: Molecular and Cellular Biochemistry. 1999 September; 199(1-2): 15-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10544947&dopt=Abstract

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Syndrome of infantile osteopetrosis and Hirschsprung disease in seven children born to four consanguineous unions in two families. Author(s): Dudin AA, Rambaud-Cousson A. Source: American Journal of Medical Genetics. 1993 November 15; 47(7): 1083-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8291528&dopt=Abstract

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Syndrome of osteopetrosis and muscular degeneration associated with cerebro-oculofacio-skeletal changes. Author(s): Lerman-Sagie T, Levi Y, Kidron D, Grunebaum M, Nitzan M. Source: American Journal of Medical Genetics. 1987 September; 28(1): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3674107&dopt=Abstract

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Temporal bone histopathology of osteopetrosis. Author(s): Suga F, Linsay JR. Source: The Annals of Otology, Rhinology, and Laryngology. 1976 January-February; 85(1 Pt 1): 15-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1083183&dopt=Abstract

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Temporal bone pathology of adult-type osteopetrosis. Author(s): Milroy CM, Michaels L. Source: Archives of Otolaryngology--Head & Neck Surgery. 1990 January; 116(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2294946&dopt=Abstract

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Tetracycline-based analysis of bone remodelling in osteopetrosis. Author(s): Frost HM, Vilanueva AR, Jett S, Eyring E. Source: Clinical Orthopaedics and Related Research. 1969 July-August; 65: 203-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5802527&dopt=Abstract

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The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part IV of IV parts: The state of the bones in uremic hyperaparathyroidism--the mechanisms of skeletal resistance to PTH in renal failure and pseudohypoparathyroidism and the role of PTH in osteoporosis, osteopetrosis, and osteofluorosis. Author(s): Parfitt AM. Source: Metabolism: Clinical and Experimental. 1976 October; 25(10): 1157-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=787723&dopt=Abstract

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The association of infantile osteopetrosis and neuronal storage disease in two brothers. Author(s): Jagadha V, Halliday WC, Becker LE, Hinton D. Source: Acta Neuropathologica. 1988; 75(3): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3348081&dopt=Abstract

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The detection of extramedullary hematopoiesis in a patient with osteopetrosis. Author(s): Adams BK, Smuts NA. Source: European Journal of Nuclear Medicine. 1989; 15(12): 803-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2625128&dopt=Abstract

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The hematopoietic effects of prednisone therapy in four infants with osteopetrosis. Author(s): Reeves JD, Huffer WE, August CS, Hathaway WE, Koerper M, Walters CE. Source: The Journal of Pediatrics. 1979 February; 94(2): 210-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=762608&dopt=Abstract

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The influence of thyroid hormones on bone turnover in health and osteopetrosis. Author(s): Langdahl BL, Eriksen EF. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1998 July; 139(1): 10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9703369&dopt=Abstract

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The jaws in osteopetrosis (Albers-Schonberg disease): report of case. Author(s): Gomez LS, Taylor R, Cohen MM, Shklar G. Source: J Oral Surg. 1966 January; 24(1): 67-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5214564&dopt=Abstract

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The mutational spectrum of human malignant autosomal recessive osteopetrosis. Author(s): Sobacchi C, Frattini A, Orchard P, Porras O, Tezcan I, Andolina M, BabulHirji R, Baric I, Canham N, Chitayat D, Dupuis-Girod S, Ellis I, Etzioni A, Fasth A, Fisher A, Gerritsen B, Gulino V, Horwitz E, Klamroth V, Lanino E, Mirolo M, Musio A, Matthijs G, Nonomaya S, Notarangelo LD, Ochs HD, Superti Furga A, Valiaho J, van Hove JL, Vihinen M, Vujic D, Vezzoni P, Villa A. Source: Human Molecular Genetics. 2001 August 15; 10(17): 1767-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532986&dopt=Abstract

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The pathogenesis of infantile malignant osteopetrosis: bone mineral metabolism and complications in five infants. Author(s): Reeves J, Arnaud S, Gordon S, Subryan B, Block M, Huffer W, Arnaud C, Mundy G, Haussler M. Source: Metab Bone Dis Relat Res. 1981; 3(2): 135-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6270498&dopt=Abstract

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The protein tyrosine kinase p60c-Src is not implicated in the pathogenesis of the human autosomal recessive form of osteopetrosis: a study of 13 children. Author(s): Bernard F, Casanova JL, Cournot G, Jabado N, Peake J, Jauliac S, Fischer A, Hivroz C. Source: The Journal of Pediatrics. 1998 October; 133(4): 537-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9787694&dopt=Abstract

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The role of carbonic anhydrase in autosomal dominant osteopetrosis. Author(s): Bollerslev J, Mondrup MP. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1989 February; 49(1): 93-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2499032&dopt=Abstract

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The syndrome of osteopetrosis in siblings: its occurrence in two sisters in Nigeria. Author(s): Adeloye A. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1987; 3(2): 128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3621230&dopt=Abstract

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The syndrome of osteopetrosis, renal acidosis and cerebral calcification in two sisters. Author(s): Al Rajeh S, el Mouzan MI, Ahlberg A, Ozaksoy D. Source: Neuropediatrics. 1988 August; 19(3): 162-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3221988&dopt=Abstract

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The temporal bone in osteopetrosis. Author(s): Myers EN, Stool S. Source: Arch Otolaryngol. 1969 March; 89(3): 460-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5304350&dopt=Abstract

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Therapeutic studies in osteopetrosis. Report of 4 cases. Author(s): Moe PJ, Skjaeveland A. Source: Acta Paediatr Scand. 1969 November; 58(6): 593-600. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5378349&dopt=Abstract

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Thermal stability of cortical bone collagen in relation to age in normal individuals and in individuals with osteopetrosis. Author(s): Danielsen CC, Mosekilde L, Bollerslev J, Mosekilde L. Source: Bone. 1994 January-February; 15(1): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8024858&dopt=Abstract

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Three sibs with mild variety of osteopetrosis. Author(s): Shah AM, Boby KF, Karande SC, Lahiri KR, Jain MK. Source: Journal of Postgraduate Medicine. 1996 October-December; 42(4): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9715315&dopt=Abstract

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Thymus and osteopetrosis. Author(s): Milhaud G, Labat ML. Source: Clinical Orthopaedics and Related Research. 1978 September; (135): 260-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=361322&dopt=Abstract

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Thyroid hormone resistance in blood monocyte cells and elevated serum T3 in patients with autosomal dominant osteopetrosis. Author(s): Bollerslev J, Kvetny J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1988 December; 48(8): 795-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3238324&dopt=Abstract

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Total decompression of the facial nerve in osteopetrosis (marble bone disease-morbus Albers-Schonberg). Author(s): Hamersma H. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 1974; 36(1): 21-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4361518&dopt=Abstract

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Total hip arthroplasty in osteopetrosis. A report of two cases. Author(s): Ashby ME. Source: Clinical Orthopaedics and Related Research. 1992 March; (276): 214-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1537156&dopt=Abstract

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Transfusion of carbonic anhydrase-replete erythrocytes fails to correct the acidification defect in the syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification (carbonic anhydrase-II deficiency). Author(s): Whyte MP, Hamm LL 3rd, Sly WS. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1988 August; 3(4): 385-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3146897&dopt=Abstract

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Transient infantile osteopetrosis. Author(s): Monaghan BA, Kaplan FS, August CS, Fallon MD, Flannery DB. Source: The Journal of Pediatrics. 1991 February; 118(2): 252-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1993956&dopt=Abstract

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Transplantation of cord blood progenitor cells can promote bone resorption in autosomal recessive osteopetrosis. Author(s): Locatelli F, Beluffi G, Giorgiani G, Maccario R, Fiori P, Pession A, Bonetti F, Comoli P, Calcaterra V, Rondini G, Severi F. Source: Bone Marrow Transplantation. 1997 October; 20(8): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383237&dopt=Abstract

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Triiodothyronine stimulates urinary excretion of calcium and hydroxyproline in autosomal dominant osteopetrosis. Author(s): Bollerslev J, Nielsen HK, Kvetny J, Mosekilde L. Source: Bone. 1988; 9(4): 205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3166837&dopt=Abstract

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Two cases of osteopathia striata, deafness and cranial osteopetrosis. Author(s): Franklyn PP, Wilkinson D. Source: Ann Radiol (Paris). 1978 March-April; 21(2-3): 91-3. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=677756&dopt=Abstract

·

Type II autosomal dominant osteopetrosis (Albers-Schonberg disease): clinical and radiological manifestations in 42 patients. Author(s): Benichou OD, Laredo JD, de Vernejoul MC. Source: Bone. 2000 January; 26(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617161&dopt=Abstract

·

Type II autosomal dominant osteopetrosis. Author(s): Senel K, Ugur M, Erdal A, Ozdemir H. Source: Rheumatology International. 2002 July; 22(3): 116-8. Epub 2002 May 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111087&dopt=Abstract

·

Ultrastructural abnormalities of osteoclasts in malignant-recessive osteopetrosis. Author(s): Shapiro F. Source: Archives of Pathology & Laboratory Medicine. 1982 August; 106(8): 425. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6896634&dopt=Abstract

·

Ultrastructural findings of bone marrow in a case with malignant osteopetrosis following successful allogeneic bone marrow transplantation. Author(s): Korkusuz P, Asan E, Cetin M, Tuncer M, Tezcan I. Source: Turk J Pediatr. 1999 July-September; 41(3): 353-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770097&dopt=Abstract

90 Osteopetrosis

·

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis. Author(s): Bollerslev J, Marks SC Jr, Pockwinse S, Kassem M, Brixen K, Steiniche T, Mosekilde L. Source: Bone. 1993 November-December; 14(6): 865-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8155410&dopt=Abstract

·

Ultrastructure of macrophages and dendritic cells in osteopetrosis (op) mutant mice lacking macrophage colony-stimulating factor (M-CSF/CSF-1) activity. Author(s): Usuda H, Naito M, Umeda S, Takahashi K, Shultz LD. Source: J Submicrosc Cytol Pathol. 1994 January; 26(1): 111-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8149328&dopt=Abstract

·

Valgus tibial osteotomy in a patient with benign dominant osteopetrosis (AlbersSchoenberg disease). A case report. Author(s): Stalder H, von Hochstetter A, Schreiber A. Source: International Orthopaedics. 1994 October; 18(5): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7852011&dopt=Abstract

·

Variable osteoclast appearance in human infantile osteopetrosis. Author(s): Shapiro F, Key LL, Anast C. Source: Calcified Tissue International. 1988 August; 43(2): 67-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3142669&dopt=Abstract

·

Visual loss in infantile osteopetrosis. Author(s): Ainsworth JR, Bryce IG, Dudgeon J. Source: Journal of Pediatric Ophthalmology and Strabismus. 1993 May-June; 30(3): 2013. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8350232&dopt=Abstract

·

Visual loss in osteopetrosis. Author(s): Hoyt CS, Billson FA. Source: Am J Dis Child. 1979 September; 133(9): 955-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=474548&dopt=Abstract

91

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

Finding Nutrition Studies on Osteopetrosis 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 “osteopetrosis” (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.

92 Osteopetrosis

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

Assessment of the influence of NaF or 1,25-(OH)2 vitamin D3 on the proliferative bone effect of an avian osteopetrosis virus, MAV-2(O). Author(s): Department of Microbiology, Colorado State University, Fort Collins 80523. Source: Smith, R E Maurer, J K Long, P H Proctor, J E Torgersen, J L Toxicol-Pathol. 1990; 18(3): 380-6 0192-6233

·

Autosomal dominant osteopetrosis: bone metabolism and epidemiological, clinical, and hormonal aspects. Author(s): Department of Internal Medicine, Svendborg Hospital, Denmark. Source: Bollerslev, J Endocr-Revolume 1989 February; 10(1): 45-67 0163-769X

·

Biochemical markers of bone metabolism in benign human osteopetrosis: a study of two types at baseline and during stimulation with triiodothyronine. Author(s): Department of Medical Endocrinology, National University Hospital, Oslo, Norway. Source: Bollerslev, J Ueland, T Grodum, E HAugust, E Brixen, K Djoseland, O Eur-JEndocrinol. 1998 July; 139(1): 29-35 0804-4643

·

Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant. Author(s): Centre de Recherche Guy Bernier et Unite de Greffe de Moelle Osseuse,Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada. Source: Lajeunesse, D Busque, L Menard, P Brunette, M G Bonny, Y J-Clin-Invest. 1996 October 15; 98(8): 1835-42 0021-9738

·

Dual-energy x-ray absorptiometry in osteopetrosis. Author(s): Department of Radiology, Arkansas Children's Hospital, Little Rock, USA. Source: Adler, I N Stine, K C Kurtzburg, J Kinder, D L Cox, K S Lensing, S Y Seibert, J J South-Med-J. 2000 May; 93(5): 501-3 0038-4348

·

Experimental studies of osteopetrosis in laboratory animals. Author(s): Department of Anatomy, Indiana University Medical Center, Indianapolis 46202. Source: Seifert, M F Popoff, S N Jackson, M E MacKay, C A Cielinski, M Marks, S C ClinOrthopage 1993 September; (294): 23-33 0009-921X

·

Failure of calcitriol treatment in a patient with malignant osteopetrosis. Author(s): Department of Paediatrics, Academic Hospital Leyden, The Netherlands. Source: van Lie Peters, E M Aronson, D C Everts, V Dooren, L J Eur-J-Pediatr. 1993 October; 152(10): 818-21 0340-6199

·

Increased urine heparan and chondroitin sulphate excretion in patients with osteopetrosis. Author(s): Department of Pediatrics, Oregon Health Sciences University, Portland, USA. Source: Steiner, R D Whyte, M P Chang, E Hanks, J Mattes, C Senephansiri, H Gibson, K M J-Inherit-Metab-Dis. 2000 February; 23(1): 88-90 0141-8955

·

Malignant osteopetrosis obscured by maternal vitamin D deficiency in a neonate. Author(s): Department of Pediatrics, University of Heidelberg, Germany. [email protected] Source: Popp, D Zieger, B Schmitt Graff, A Nutzenadel, W Schaefer, F Eur-J-Pediatr. 2000 June; 159(6): 412-5 0340-6199

Nutrition 93

·

Malignant osteopetrosis treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Author(s): Department of Pediatrics, Okayama University Medical School, Japan. Source: Kubo, T Tanaka, H Ono, H Moriwake, T Kanzaki, S Seino, Y J-Pediatr. 1993 August; 123(2): 264-8 0022-3476

·

Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation. Author(s): Department of Haematology, Royal Infirmary, Glasgow. Source: Rawlinson, P S Green, R H Coggins, A M Boyle, I T Gibson, B E Arch-Dis-Child. 1991 May; 66(5): 638-9 0003-9888

·

Managing osteopetrosis in children: a nutrition challenge. Author(s): Department of Food and Nutrition Services, St Jude Children's Research Hospital, Memphis, Tenn. 38101, USA. Source: Williams, R Wang, W J-Am-Diet-Assoc. 1996 February; 96(2): 172-5 0002-8223

·

Mineral metabolism in infants with malignant osteopetrosis: heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology. Author(s): CNRS URA 583, Universite Paris V, France. Source: Cournot, G Trubert Thil, C L Petrovic, M Boyle, A Cormier, C Girault, D Fischer, A Garabedian, M J-Bone-Miner-Res. 1992 January; 7(1): 1-10 0884-0431

·

Neonatal reductions in osteoclast number and function account for the transient nature of osteopetrosis in the rat mutation microphthalmia blanc (mib). Author(s): Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655. Source: Cielinski, M J Marks, S C Bone. 1994 Nov-December; 15(6): 707-15 8756-3282

·

Normalization of mineral homeostasis after reversal of osteopetrosis. Author(s): Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. Source: Nesbitt, T Marks, S C Jackson, M E Mackay, C A Drezner, M K J-Bone-MinerRes. 1995 July; 10(7): 1116-21 0884-0431

·

Osteopetrosis in the rat: coexistence of reductions in osteocalcin and bone resorption. Author(s): Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655. Source: Lian, J B Marks, S C Endocrinology. 1990 February; 126(2): 955-62 0013-7227

·

Osteopetrosis. Current clinical considerations. Author(s): Department of Orthopaedic Surgery, Children's Hospital, Boston, MA 02115. Source: Shapiro, F Clin-Orthopage 1993 September; (294): 34-44 0009-921X

·

Osteopetrosis. The pharmaco-physiologic basis of therapy. Author(s): Department of Pediatrics, Brenner Children's Hospital, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina. Source: Key, L L Ries, W L Clin-Orthopage 1993 September; (294): 85-9 0009-921X

·

Recombinant human interferon gamma therapy for osteopetrosis. Author(s): Department of Pediatrics, Medical University of South Carolina, Charleston 29425. Source: Key, L L Ries, W L Rodriguiz, R M Hatcher, H C J-Pediatr. 1992 July; 121(1): 11924 0022-3476

·

Rickets, osteomalacia, and osteopetrosis. Author(s): Hopital Necker, Paris, France.

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Source: Balsan, S Garabedian, M Curr-Opin-Rheumatol. 1991 June; 3(3): 496-502 10408711 ·

Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types. Author(s): Department of Internal Medicine, Svendborg Hospital, Denmark. Source: Bollerslev, J Nielsen, H K Storm, T Mosekilde, L Bone. 1988; 9(6): 355-9 87563282

·

Superoxide generation in transformed B-lymphocytes from patients with severe, malignant osteopetrosis. Author(s): Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA. Source: Yang, S Ries, W L Key, L L Mol-Cell-Biochem. 1999 September; 199(1-2): 15-24 0300-8177

·

The role of macrophage colony-stimulating factor in hepatic glucan-induced granuloma formation in the osteopetrosis mutant mouse defective in the production of macrophage colony-stimulating factor. Author(s): Second Department of Pathology, Kumamoto University School of Medicine, Japan. Source: Takahashi, K Naito, M Umeda, S Shultz, L D Am-J-Pathol. 1994 June; 144(6): 1381-92 0002-9440

·

Treatment of congenital osteopetrosis in the rabbit with high-dose 1,25dihydroxyvitamin D. Author(s): Department of Cell Biology, University of Massachusetts Medical School, Worcester. Source: Popoff, S N McGuire, J L Zerwekh, J E Marks, S C J-Bone-Miner-Res. 1989 February; 4(1): 57-67 0884-0431

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

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

·

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

·

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

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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/

·

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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WebMDÒHealth: http://my.webmd.com/nutrition

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

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CHAPTER 3. OSTEOPETROSIS

ALTERNATIVE

MEDICINE

AND

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

1alpha-hydroxyvitamin D3 in the treatment of nutritional and metabolic rickets and osteomalacia. Author(s): Gertner JM, Brenton DB, Edwards RH. Source: Clinical Endocrinology. 1977 December; 7 Suppl: 239S-244S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=203419&dopt=Abstract

·

Auditory brainstem responses (ABR) in children with neurological disorders. Author(s): el Khateeb I, Abdul Razzak B, Moosa A. Source: Brain & Development. 1988; 10(4): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3218703&dopt=Abstract

·

Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating

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factor-1. Author(s): Aharinejad S, Grossschmidt K, Franz P, Streicher J, Nourani F, MacKay CA, Firbas W, Plenk H Jr, Marks SC Jr. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1999 March; 14(3): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027906&dopt=Abstract ·

Comparative study on the composition of the organic matrix of the long bones of the “normal” rat and of the mutant Op/Orl. Author(s): Moczar E, Berenholc S, Lamendin H, Allard R, Robert AM. Source: Pathologie-Biologie. 1977 March; 25(3): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=404616&dopt=Abstract

·

Defects in growth and bone metabolism in klotho mutant mice are resistant to GH treatment. Author(s): Kashimada K, Yamashita T, Tsuji K, Nifuji A, Mizutani S, Nabeshima Y, Noda M. Source: The Journal of Endocrinology. 2002 September; 174(3): 403-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208660&dopt=Abstract

·

Experimental studies of osteopetrosis in laboratory animals. Author(s): Seifert MF, Popoff SN, Jackson ME, MacKay CA, Cielinski M, Marks SC Jr. Source: Clinical Orthopaedics and Related Research. 1993 September; (294): 23-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8358920&dopt=Abstract

·

Hyperbaric oxygen treatment of mandibular osteomyelitis in osteopetrosis. Author(s): Mainous EG, Hart GB, Soffa DJ, Graham GA. Source: J Oral Surg. 1975 April; 33(4): 288-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1054401&dopt=Abstract

·

Rehabilitation of left femur subtrochanteric fracture in osteopetrosis -- a case report. Author(s): Yang BJ, Chen CF, Lien IN. Source: Taiwan Yi Xue Hui Za Zhi. 1980 December; 79(12): 1180-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6943297&dopt=Abstract

·

Treatment of congenital osteopetrosis in the rabbit with high-dose 1,25dihydroxyvitamin D. Author(s): Popoff SN, McGuire JL, Zerwekh JE, Marks SC Jr.

Alternative Medicine 99

Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1989 February; 4(1): 57-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2718779&dopt=Abstract ·

Treatment of congenital osteopetrosis with high-dose calcitriol. Author(s): Key L, Carnes D, Cole S, Holtrop M, Bar-Shavit Z, Shapiro F, Arceci R, Steinberg J, Gundberg C, Kahn A, et al. Source: The New England Journal of Medicine. 1984 February 16; 310(7): 409-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6546410&dopt=Abstract

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

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

·


·

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

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

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

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

·

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

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

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

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

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WebMDÒHealth: http://my.webmd.com/drugs_and_herbs

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

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

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

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CHAPTER 4. CLINICAL TRIALS AND OSTEOPETROSIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning osteopetrosis.

Recent Trials on Osteopetrosis The following is a list of recent trials dedicated to osteopetrosis.8 Further information on a trial is available at the Web site indicated. ·

Post marketing surveillance study of Actimmune in patients with severe, malignant osteopetrosis. Condition(s): Osteopetrosis Study Status: This study is currently recruiting patients. Sponsor(s): InterMune Pharmaceuticals Purpose - Excerpt: The purpose of this study is to establish a registry of all children with severe, malignant osteopetrosis who are treated with Actimmune (IFN-g 1b or Interferon gamma-1b) to monitor the effects of IFN-g 1b on preventing progression of this disease and to follow the safety of patients receiving it on a long-term basis. In addition, evaluation of the possible effect of Actimmune therapy on the humoral response to normal childhood vaccinations in this same patient population will be examined.Interferon gamma is a substance that the body makes naturally. Phase(s): Phase IV Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043329

8

These are listed at www.ClinicalTrials.gov.

102 Osteopetrosis

·

Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis Condition(s): Osteopetrosis Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; Medical University of South Carolina Purpose - Excerpt: Objectives: I. Compare the rate of treatment failure in osteopetrosis patients receiving interferon gamma in combination with calcitriol to the rate of treatment failure in patients receiving calcitriol alone. II. Compare the number of adverse events or clinical manifestations of disease progression occurring in these patients. III. Assess the effects of interferon gamma on hematopoiesis, cranial nerve function, and rate of infection in these patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004402

·

Study of Unrelated Allogeneic Bone Marrow Transplantation in Patients With Benign Congenital Bone Marrow Failure Disorders Condition(s): Graft Versus Host Disease; Neutropenia; Shwachman syndrome; Red-Cell Aplasia, Pure; Osteopetrosis Study Status: This study is not yet open for patient recruitment. Sponsor(s): Fairview University Medical Center Purpose - Excerpt: Objectives: I. Deliver potential curative therapy with unrelated donor bone marrow transplantation in patients with Kostman's neutropenia, Shwachman's neutropenia, Diamond-Blackfan anemia, or autosomal recessive osteopetrosis.. II. Determine the rate of engraftment following transplantation of nongenotypic identical bone marrow with partial lymphocyte depletion using a preparative regimen consisting of busulfan, cyclophosphamide, anti-thymocyte globulin and radiotherapy in this patient population. III. Determine the incidence of acute and chronic graft vs host disease, relapse, and three year survival in this patient population treated with this regimen. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005895

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately

Clinical Trials 103

5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “osteopetrosis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: ·

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

·

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

·

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

·

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

·

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

·

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

·

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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

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

·

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

·

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

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CHAPTER 5. PATENTS ON OSTEOPETROSIS 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.9 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 “osteopetrosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on osteopetrosis, we have not necessarily excluded nonmedical patents in this bibliography.

Patent Applications on Osteopetrosis As of December 2000, U.S. patent applications are open to public viewing.10 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 osteopetrosis:

9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 10 This has been a common practice outside the United States prior to December 2000.

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·

Preparation of potent macrophage activating factors derived from cloned vitamin D binding protein and its domain and their therapeutic usage for cancer, HIV-infection and osteopetrosis Inventor(s): Yamamoto, Nobuto; (Philadelphia, PA) Correspondence: CAESAR, RIVISE, BERNSTEIN,; COHEN & POKOTILOW, LTD. 12TH FLOOR, SEVEN PENN CENTER; 1635 MARKET STREET; PHILADELPHIA; PA; 191032212; US Patent Application Number: 20020055140 Date filed: April 5, 2001 Abstract: Vitamin D-binding protein (Gc protein) and its small domain (approximately 1/5 of the Gc peptide also known as domain III) were cloned via a baculovirus vector. The cloned Gc protein and the cloned domain (Cd) peptide were treated with immobilized.beta.-galactosidase and sialidase to yield macrophage activating factors, GcMAFc and CdMAF, respectively. These cloned macrophage activating factors and GcMAF are to be used for therapy of cancer, HIV-infection and osteopetrosis, and may also be used as adjuvants for immunization and vaccination. Excerpt(s): This invention relates to potent macrophage activating factors, prepared by oligosaccharide digestion of the cloned vitamin D binding protein (Gc protein) and the cloned Gc protein domain III, and the use of these macrophage activating factors for various cancer, HIV-infection and osteopetrosis, and as adjuvants for immunization and vaccination.... Vitamin D-binding protein (Gc protein) and its small domain (approximately 1/5 of the Gc peptide also known as domain III) were cloned via a baculovirus vector. The cloned Gc protein and the cloned domain (Cd) peptide were treated with immobilized.beta.-galactosidase and sialidase to yield macrophage activating factors, GcMAFc and CdMAF, respectively. These cloned macrophage activating factors and GcMAF are to be used for therapy of cancer, HIV-infection and osteopetrosis, and may also be used as adjuvants for immunization and vaccination.... Inflammation results in the activation of macrophages. Inflamed lesions release lysophospholipids. The administration into mice of small doses (5-20.mu.g/mouse) of lysophosphatidylcholine (lyso-Pc) and other lysophospholipids induced a greatly enhanced phagocytic and superoxide generating capacity of macrophages (Ngwenya and Yamamoto, Proc. Soc. Exp. Biol. Med. 193:118, 1990; Yamamoto et al, Inf. Imm. 61:5388, 1993; Yamamoto et al., Inflammation. 18:311, 1994). 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 osteopetrosis, 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 “osteopetrosis” (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 osteopetrosis.

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You can also use this procedure to view pending patent applications concerning osteopetrosis. 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 6. BOOKS ON OSTEOPETROSIS Overview This chapter provides bibliographic book references relating to osteopetrosis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on osteopetrosis 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 “osteopetrosis” (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 osteopetrosis: ·

Otosclerosis: Diagnosis and Treatment Source: Alexandria, VA: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. (AAO-HNS). 1993. 90 p. Contact: American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc. (AAO-HNS). One Prince Street, Alexandria, VA 22314. (703) 836-4444. Fax (703) 6835100. PRICE: $20.00 for AAO-HNS members; $25.00 for nonmembers. Item Number 5506210. ISBN: 1567720072. Summary: This Self-Instructional Package (SIPac) booklet serves as a clinical reference on otosclerosis for residents in otolaryngology-head and neck surgery. Topics include a definition of otosclerosis; the etiology, pathology and anatomy of otosclerosis; clinicopathologic correlations; the patient history and examination, including audiometric tests and radiologic studies; the differential diagnosis of otosclerosis, including comparison to congenital malleus or incus fixation, congenital stapes fixation,

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other congenital ossicular abnormalities, postinflammatory ossicular fixation, ossicular discontinuity, osteogenesis imperfecta tarda, Paget's disease, and osteopetrosis; the management of otosclerosis, including observation, prosthetic rehabilitation, medical treatment, and surgery; and the complications of stapedectomy and their management. The self-paced instruction style includes pre-tests for self assessment, interim quizzes for each chapter, and a post-test. 28 figures. 48 references.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “osteopetrosis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 ·

Osteoporosis sourcebook: basic consumer health information about primary and secondary osteoporosis and juvenile osteoporosis and related conditions: including fibrous dysplasia, Gaucher disease, hyperthyroidism, hypophosphatasia, myeloma, osteopetrosis, osteogenesis imperfecta, and Paget's disease: along with information about risk factors, treatments, traditional and nontraditional pain management, a glossary or related terms , and a directory of resources Author: Cook, Allan R.; Year: 1953; Detroit, MI: Omnigraphics, 2001; ISBN: 078080239X http://www.amazon.com/exec/obidos/ASIN/078080239X/icongroupinterna

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

Temporal Bone Granulomas and Dystrophies Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 801-811.

11

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

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Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: Granulomatous disease and osteodystrophy are a diverse group of disorders that include osseous dysplasia, histiocytic proliferation, autoimmune disorders, and infectious diseases. This chapter on temporal bone granulomas and dystrophies is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. The authors discuss osteodystrophies and dysplasias, including Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, osteopetrosis, endosteal hyperostosis, and osteitis fibrosa cystica; histiocytic proliferation, notably Langerhans cell histiocytosis; and autoimmune disorders, including Wegener's granulomatosis and sarcoidosis. The authors note that most of these processes are not common, but they are important to otolaryngologists. Local behavior can be aggressive, and audiologic, vestibular, or facial nerve dysfunction can result. 5 figures. 1 table. 73 references. ·

Fibro-Osseous Diseases and Systemic Diseases Affecting Bone Source: in Marx, R.E. Stern, D. Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment. Chicago, IL: Quintessence Publishing Co, Inc. 2003. p.739-770. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $ 399.00 plus shipping and handling. ISBN: 0867153903. Summary: This chapter on fibro-osseous diseases and systemic disease affecting bone is from a clinically oriented guide for oral and maxillofacial surgeons and other advanced dental and medical specialists who deal with pathologies in the oral cavity, midface, and neck. Topics include primary hyperparathyroidism, secondary hyperparathyroidism, hypercalcemia of malignancy, cherubism, fibrous dysplasia, cemento-osseous dysplasia, nonspecific radiopacities of the jaws, Paget disease, osteopetrosis, the effects of calcium, phosphate, and alkaline phosphatase in fibro-osseous diseases, and severe anemias affecting bone. For each condition, the authors discuss clinical presentation and pathogenesis, differential diagnosis, diagnostic work-up, histopathology, treatment, and prognosis. Full-color photographs illustrate the chapter. 29 figures.

·

Metabolic and Genetic Jaw Diseases Source: in Regezi, J.A. and Sciubba, J.J. Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 417-452. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32821-9854. (800) 545-2522. Fax (800) 874-6418. Website: www.wbsaunders.com. PRICE: $63.95. ISBN: 0721677312. Summary: This chapter on metabolic and genetic jaw diseases is from a pathology textbook that presents current concepts of oral and maxillofacial pathology in order to enhance the reader's diagnostic skills through the use of differential diagnosis strategies. The text offers readers detailed guidance of etiology, pathogenesis, clinical features, histopathology, differential diagnosis, and treatment of oral diseases of the mucosa, submucosa, and bone. This chapter covers metabolic conditions, including Paget's

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disease, hyperparathyroidism, hyperthyroidism, hypophosphatasia, infantile cortical hyperostosis, phantom bone disease, and acromegaly; and genetic abnormalities, including cherubism, osteopetrosis, osteogenesis imperfecta, cleidocranial dysplasia, Crouzon's syndrome (craniofacial dysostosis), Treacher Collins syndrome (mandibulofacial dysostosis), Pierre Robin syndrome, Marfan's syndrome, Ehlers Danlos syndrome, Down syndrome (trisomy 21), hemifacial atrophy, hemifacial hypertrophy, clefts of the lip and palate, and Fragile X syndrome. 32 figures. 142 references. ·

Musculoskeletal Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 310-335. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on musculoskeletal disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. The authors note that the jaws and temporomandibular joints are part of the skeletal system, but are rarely involved by systemic disease and few skeletal diseases affect the management of the dental patient directly. Muscle disorders are relatively uncommon and involvement of the masticatory (chewing) and facial muscles is not necessarily a prominent feature. However, for patients with musculoskeletal disease, access to the dental clinic or getting into or out of the chair may be difficult. Topics include genetic skeletal diseases, osteogenesis imperfecta, achondroplasia, cleidocranial dysplasia, osteopetrosis (Albers Schonberg disease), Marfan's syndrome, Ehlers Danlos syndrome, diseases of calcium metabolism and bone, rickets and osteomalacia, osteoporosis, William's syndrome, tumoral calcinosis, fibrous dysplasia, Paget's disease of bone (osteitis deformans), osteoarthritis, rheumatoid arthritis, Felty's syndrome, juvenile rheumatoid arthritis (childhood polyarthritis), psoriatic arthritis, Lyme disease, gout, ankylosing spondylitis, Reiter's disease, prosthetic joint replacements, genetic myopathies, polymyositis and dermatomyositis, and cranial arteritis and polymyalgia rhematica. For each condition, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 4 figures. 10 tables. 61 references.

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CHAPTER 7. PERIODICALS AND NEWS ON OSTEOPETROSIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover osteopetrosis.

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

Pamidronate linked to osteopetrosis in a child Source: Reuters Medical News Date: July 31, 2003 http://www.reutershealth.com/archive/2003/07/31/professional/links/20030731clin0 09.html

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·

FDA approves Actimmune for management of osteopetrosis Source: Reuters Medical News Date: February 14, 2000

·

Recombinant Human Interferon Gamma Benefits Some Patients With Osteopetrosis Source: Reuters Medical News Date: June 15, 1995

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

Periodicals and News 115

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 “osteopetrosis” (or synonyms).

Academic Periodicals covering Osteopetrosis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to osteopetrosis. In addition to these sources, you can search for articles covering osteopetrosis 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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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 Institute12: ·

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

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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

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

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

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

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

12

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

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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/

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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

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

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

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

·

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

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

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

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

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

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

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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.13 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:14 ·

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

·

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

·

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

·

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

·

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

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

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

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

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

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

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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

13 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). 14 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

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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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “osteopetrosis” (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 2031 14 5 1 0 2051

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “osteopetrosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

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

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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.


Coffee Break: Tutorials for Biologists20 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.21 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.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

·

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

The Genome Project and Osteopetrosis In the following section, we will discuss databases and references which relate to the Genome Project and osteopetrosis.

Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted from 21

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. 22 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. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

124 Osteopetrosis

To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “osteopetrosis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for osteopetrosis: ·

Ectodermal Dysplasia, Anhidrotic, with Immunodeficiency, Osteopetrosis, and Lymphedema Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300301

·

Osteopetrosis and Infantile Neuroaxonal Dystrophy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600329

·

Osteopetrosis with Renal Tubular Acidosis Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259730

·

Osteopetrosis, Autosomal Dominant, Type I Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607634

·

Osteopetrosis, Autosomal Dominant, Type Ii Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?166600

·

Osteopetrosis, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259700

·

Osteopetrosis, Lethal Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259720

·

Osteopetrosis, Mild Autosomal Recessive Form Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?259710

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

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

·

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


·

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

·

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

·

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

·

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

·

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

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

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

·

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

·

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

·

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

·

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

·

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

126 Osteopetrosis

·

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

·

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

·

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

·

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

·

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

·

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

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “osteopetrosis” (or synonyms) into the search box and click “Go.”

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.


scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “osteopetrosis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

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

130 Osteopetrosis

·

Other guides Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html Foot Injuries and Disorders http://www.nlm.nih.gov/medlineplus/footinjuriesanddisorders.html Fractures http://www.nlm.nih.gov/medlineplus/fractures.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Stem Cells/Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsstemcelltransplantation.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on osteopetrosis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: ·

Questions and Answers About Osteopetrosis Source: New York, NY: Paget Foundation. 1998. 13 p. Contact: Available from Paget Foundation. 120 Wall Street, Suite 1602, New York, NY 10005-4001. (212) 509-5335. Fax (212) 509-8492. E-mail: [email protected]. Website: www.paget.org. PRICE: Single copy free plus $2.00 shipping and handling. Summary: This brochure uses a question and answer format to provide people who have osteopetrosis with information on this congenital condition, which is characterized by overly dense bones. Questions deal with the bones most commonly affected by osteopetrosis, its symptoms, the three different types of osteopetrosis, their common features, and the reason the malignant infantile form is considered the most severe. In addition, other questions focus on the cause of osteopetrosis; the role of genetics in its etiology; its magnitude and diagnosis; and its treatment by bone marrow

Patient Resources 131

transplantation, high dose calcitriol, interferon gamma, prednisone, good nutrition, and physical and occupational therapy. Remaining questions concern the prognosis for people who have osteopetrosis, the types of physicians who diagnose and treat it, and treatment research. The brochure also includes a glossary and provides information on the Paget Foundation.

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 osteopetrosis. 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.

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

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


·

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/

·

WebMDÒHealth: http://my.webmd.com/health_topics

132 Osteopetrosis

Associations and Osteopetrosis The following is a list of associations that provide information on and resources relating to osteopetrosis: ·

March of Dimes Birth Defects Foundation Telephone: (914) 428-7100 Toll-free: (888) 663-4637 Fax: (914) 997-4763 Email: [email protected] Web Site: http://www.marchofdimes.com Background: The March of Dimes Birth Defects Foundation is a national not-for-profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. The March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it also produces a wide variety of printed informational materials and videos. The Pregnancy and Newborn Health Education Center staffs trained health information specialists who provide researched information on pregnancy issues, complications and risks, newborn care, birth defects, genetic diseases and related topics as well as referrals to relevant organizations and support groups. Relevant area(s) of interest: Osteopetrosis

·

Paget Foundation for Paget's Disease of Bone and Related Disorders Telephone: (212) 509-5335 Toll-free: (800) 237-2438 Fax: (212) 509-8492 Email: [email protected] Web Site: http://www.paget.org Background: The Paget Foundation is a voluntary health agency devoted to serving people affected by Paget s Disease of Bone and certain other bone disorders, including primary hyperparathyroidism, fibrous dysplasia, osteopetrosis, and the complications of certain cancers of the skeleton. Established in 1978, it continues to provide affected individuals and their families with up-to-date information about these disorders. It also provides physician referrals, information to enhance public awareness of Paget s Disease of Bone and related disorders, and professional education for members of the medical community. Relevant area(s) of interest: Osteopetrosis

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

Patient Resources 133

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 osteopetrosis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “osteopetrosis” (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 “osteopetrosis”. 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 “osteopetrosis” (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 “osteopetrosis” (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.26

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

26

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

136 Osteopetrosis

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)27: ·

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/

27

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

Finding Medical Libraries 137

·

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/

138 Osteopetrosis

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

·

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

Finding Medical Libraries 139

·

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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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

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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).

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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OSTEOPETROSIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Acyl: Chemical signal used by bacteria to communicate. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element,

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organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Cell: A type of cell in the pancreas (in areas called the islets of Langerhans). Alpha cells make and release a hormone called glucagon, which raises the level of glucose (sugar) in the blood. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] 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,

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magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anabolic: Relating to, characterized by, or promoting anabolism. [EU] 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] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH]

Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH]

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Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA

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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] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] 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] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH]

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Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH]

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Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [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]

Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [NIH]

Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bony Callus: The bony deposit formed between and around the broken ends of a fractured bone during normal healing. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

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Breakdown: A physical, metal, or nervous collapse. [NIH] Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [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] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU]

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Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [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] 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] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH]

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Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic examination. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrogenesis: The formation of cartilage. This process is directed by chondrocytes which continually divide and lay down matrix during development. It is sometimes a precursor to osteogenesis. [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]

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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 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] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [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 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,

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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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] 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 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT)

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scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Connective tissue: The supporting or framework tissue of the animal body, formed of fibrous and ground substance with more or less numerous cells of various kinds. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Corpus: The body of the uterus. [NIH] Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH]

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Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH]

Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU]

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Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Duct: A tube through which body fluids pass. [NIH]

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Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [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] Dysostosis: Defective bone formation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [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 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] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] 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

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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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [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 Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH]

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Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excrete: To get rid of waste from the body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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]

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Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of microfilaments

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terminate and attach to the transmembrane linkers, integrins, which in turn attach through their extracellular domains to extracellular matrix proteins. [NIH] Follicles: Shafts through which hair grows. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes bony callus formation and normal replacement of bone tissue. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH]

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Germ Layers: The three layers of cells comprising the early embryo. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [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] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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] 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] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Gonads: The gamete-producing glands, ovary or testis. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [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] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Growth: The progressive development of a living being or part of an organism from its

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earliest stage to maturity. [NIH] Growth Disorders: Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [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] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH]

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Histology: The study of tissues and cells under a microscope. [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] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperostosis: Increase in the mass of bone per unit volume. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side

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effect of some anticancer drugs. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: (antigens). [NIH]

The activity of the immune system against foreign substances

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH]

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Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Incontinentia Pigmenti: A genodermatosis occurring mostly in females and characterized by skin changes in three phases - vesiculobullous, verrucous papillomatous, and macular melanodermic. Hyperpigmentation is bizarre and irregular. Sixty percent of patients have abnormalities of eyes, teeth, central nervous system, and skin appendages. [NIH] Incus: One of three ossicles of the middle ear. It conducts sound vibrations from the malleus to the stapes. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

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

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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH]

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Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles,

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etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lacrimal: Pertaining to the tears. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] 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] 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] Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH]

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Lipid: Fat. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] 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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [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] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysophospholipids: Derivatives of phosphatidic acids that lack one of its fatty acyl chains due to its hydrolytic removal. [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 Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macrophage Colony-Stimulating Factor:

A mononuclear phagocyte colony-stimulating

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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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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] Malleus: The largest of the auditory ossicles, and the one attached to the membrana tympani (tympanic membrane). Its club-shaped head articulates with the incus. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mandibulofacial Dysostosis: A rare congenital anomaly characterized by antimongoloid oblique palpebral fissures, coloboma of the lower eyelids, hypoplasia of the facial bones, malformations of the external ears and sometimes middle and inner ears, an abnormally large mouth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger

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

Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [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] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] 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]

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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] 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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multiple 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 Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH]

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Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] 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] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH]

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Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] 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] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [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] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]

Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an

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environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Optic Atrophy: Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm, and optic tracts. Glaucoma, ischemia, inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions are relatively common causes of this condition. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossicle: A small bone. [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] Osteitis Deformans: A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry. [NIH] Osteitis Fibrosa Cystica: A fibrous degeneration, cyst formation, and the presence of fibrous nodules in bone, usually due to hyperparathyroidism. [NIH] Osteoarthritis:

A progressive, degenerative joint disease, the most common form of

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arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Osteolytic: Causing the breakdown of bone. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]

Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [NIH]

Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosclerosis: An abnormal hardening or increased density of bone tissue. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otosclerosis: The formation of spongy bone in the labyrinth capsule. The ossicles can become fixed and unable to transmit sound vibrations, thereby causing deafness. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The

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ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] 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] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Hormones: Peptide hormones secreted into the blood by cells in the Islets of Langerhans of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide. [NIH] Pancreatic Polypeptide: A 36-amino acid polypeptide with physiological regulatory functions. It is secreted by pancreatic tissue. Plasma pancreatic polypeptide increases after ingestion of food, with age, and in disease states. A lack of pancreatic polypeptide in the islets of Langerhans has been associated with the obese syndrome in rats and mice. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Paraplegia: Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with spinal cord diseases, although brain diseases; peripheral nervous system diseases; neuromuscular diseases; and muscular diseases may also cause bilateral leg weakness. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A

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sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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

Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral

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sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH]

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Plasma cells: A type of white blood cell that produces antibodies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU]

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Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the

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nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] 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]

Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Hybrid Mapping: A method for ordering genetic loci along chromosomes. The method involves fusing irradiated donor cells with host cells from another species. Following cell fusion, fragments of DNA from the irradiated cells become integrated into the chromosomes of the host cells. Molecular probing of DNA obtained from the fused cells is used to determine if two or more genetic loci are located within the same fragment of donor cell DNA. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH]

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Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines

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with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] 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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion,

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contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [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] 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] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: female or male. [NIH]

The biological characteristics which distinguish human beings as

Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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]

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Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Skull Base: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases:

Pathologic conditions which feature spinal cord damage or

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dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] 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] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spondylolysis: Dissolution of a vertebra, especially the pars interarticularis. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the 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] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain.

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[NIH]

Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtrochanteric: Below a trochanter. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Syncytium: A living nucleated tissue without apparent cellular structure; a tissue composed of a mass of nucleated protoplasm without cell boundaries. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the

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tarsus. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendinitis: Inflammation of tendons and of tendon-muscle attachments. [EU] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Theca Cells: The connective tissue cells of the ovarian follicle. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less 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 IIb-

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IIIa 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] Thrombocytopenia: A decrease in the number of blood platelets. [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]

Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] 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]

192 Osteopetrosis

Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor 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]

Dictionary 193

Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tympani: The part of the cochlea below the spiral lamina. [NIH] Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of

194 Osteopetrosis

vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [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] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [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] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

195

INDEX A Abdominal, 143, 178 Aberrant, 6, 143 Acceptor, 143, 192 Acid Phosphatase, 58, 143 Acidity, 143, 180 Acidosis, 58, 67, 87, 124, 143 Actin, 8, 20, 21, 143, 162, 172 Acyl, 143, 170 Adaptation, 7, 143 Adenine, 143 Adenocarcinoma, 11, 143 Adenosine, 54, 62, 143, 180 Adenosine Monophosphate, 54, 143 Adhesions, 22, 143 Adjustment, 143 Adrenal Cortex, 143, 145, 182 Afferent, 143, 161 Affinity, 10, 17, 143, 144, 171, 187 Agammaglobulinemia, 9, 144 Agenesis, 30, 66, 144 Agonist, 23, 144 Airway, 144, 187 Algorithms, 144, 148 Alkaline, 7, 111, 143, 144, 150, 190 Alkaline Phosphatase, 7, 111, 144 Alkylating Agents, 144, 150 Alleles, 24, 144 Allogeneic, 29, 89, 102, 144, 163 Allogeneic bone marrow transplantation, 29, 89, 144 Alopecia, 144, 156 Alpha Cell, 144, 178 Alpha Particles, 144, 183 Alternative medicine, 114, 144 Alveolar Process, 145, 184 Amino Acid Sequence, 145, 146 Amplification, 6, 145 Amygdala, 145, 148, 190 Anabolic, 7, 10, 145, 160 Anaemia, 40, 145 Anaesthesia, 43, 145, 167 Anal, 145, 161 Anaphylatoxins, 145, 154 Anatomical, 145, 152, 166, 185 Androgenic, 145 Androstenedione, 23, 145 Anemia, 81, 83, 102, 125, 145, 165, 173, 177

Animal model, 9, 13, 14, 29, 145 Anions, 24, 145, 169 Anode, 145, 146 Anorexia, 146, 177 Antibacterial, 146, 187 Antibiotic, 146, 156, 187, 188 Antibodies, 5, 15, 36, 146, 164, 166, 170, 181, 183 Antibody, 81, 144, 146, 154, 164, 165, 166, 167, 173, 183, 187 Anticoagulant, 146, 182 Antigen, 8, 144, 146, 154, 156, 163, 165, 166, 167, 168 Antigen-Antibody Complex, 146, 154 Antigen-presenting cell, 146, 156 Anti-inflammatory, 146, 163, 181 Antimicrobial, 16, 146 Antineoplastic, 144, 146, 156 Anus, 145, 146, 149, 154 Anxiety, 146, 178 Anxiety Disorders, 146, 178 Aplasia, 102, 146, 158 Apnea, 146 Apoptosis, 18, 146 Aqueous, 147, 148, 156, 158, 169 Arterial, 56, 59, 147, 165, 182, 189 Arteries, 30, 147, 149, 155, 172 Arterioles, 147, 149, 150 Arteritis, 70, 112, 147 Artery, 147, 149, 155, 179, 183 Arthroplasty, 7, 63, 67, 88, 147 Articular, 17, 147, 177 Ascorbic Acid, 147, 165 Aseptic, 147, 176, 188 Assay, 17, 19, 29, 147 Asymptomatic, 4, 147 Ataxia, 125, 147, 190 Atrophy, 34, 81, 112, 125, 147, 176 Auditory, 97, 147, 171, 193 Autologous, 46, 147 Autopsy, 74, 147 Avian, 51, 92, 147 Axillary, 147 Axonal, 78, 147 Axons, 147, 176, 185 B Bacteria, 143, 146, 147, 159, 172, 186, 187, 192, 193

196 Osteopetrosis

Bacterial Physiology, 143, 147 Basal Ganglia, 71, 147, 148, 149 Basal Ganglia Diseases, 147, 148 Base, 17, 41, 143, 148, 156, 169, 190 Basement Membrane, 148, 160 Benign, 3, 26, 32, 33, 69, 73, 77, 90, 92, 102, 148, 174, 183 Beta blocker, 11, 148 Bilateral, 32, 33, 70, 148, 178 Bile, 148, 162, 165, 170, 188 Binding Sites, 14, 148 Biochemical, 4, 8, 11, 20, 33, 50, 60, 80, 92, 144, 148, 177 Biological response modifier, 148, 168 Biological therapy, 148, 164 Biopsy, 148 Biotechnology, 25, 26, 110, 114, 121, 123, 124, 125, 126, 148 Bladder, 148, 182, 193 Bleeding Time, 148, 190 Blood Coagulation, 148, 149, 150, 191 Blood Platelets, 149, 171, 191 Blood pressure, 149, 165, 173, 181, 187 Blood vessel, 19, 148, 149, 151, 152, 153, 159, 169, 170, 172, 179, 187, 188, 190, 191, 193 Blot, 15, 149 Bone Density, 10, 149 Bone Development, 14, 149 Bone Remodeling, 8, 40, 85, 149 Bone Resorption, 4, 5, 6, 8, 9, 10, 12, 13, 16, 17, 18, 21, 22, 25, 46, 52, 67, 89, 93, 149, 150, 176 Bone scan, 67, 149 Bony Callus, 149, 162 Bowel, 145, 149, 157, 168, 188 Bowel Movement, 149, 157, 188 Brain Diseases, 149, 178 Branch, 139, 149, 158, 170, 179, 187, 190 Breakdown, 18, 150, 157, 177 Busulfan, 102, 150 C Calcifediol, 150 Calcification, 4, 36, 37, 47, 53, 58, 71, 72, 87, 88, 150 Calcinosis, 112, 150 Calcitonin, 54, 78, 150 Calcitriol, 13, 36, 45, 92, 99, 102, 131, 150 Calcium, 10, 33, 36, 53, 85, 89, 111, 112, 149, 150, 154, 162, 165, 172, 177, 179, 186, 190 Calculi, 150, 163

Callus, 47, 150, 158 Capillary, 5, 148, 150, 193 Capsid, 150, 175, 194 Carbohydrate, 150, 163, 181, 186 Carbon Dioxide, 150, 161, 184 Carcinogenic, 144, 150, 167, 176, 182, 188 Carcinogens, 151, 176 Carcinoma, 16, 78, 150, 151 Cardiac, 11, 151, 159, 160, 174, 188 Carpal Tunnel Syndrome, 28, 151 Case report, 37, 39, 43, 46, 52, 56, 60, 64, 65, 67, 68, 69, 70, 73, 74, 78, 83, 84, 90, 98, 151 Catheter, 151, 168 Catheterization, 151, 168 Cations, 151, 169 Caudal, 151, 181 Cell Adhesion, 151, 168 Cell Communication, 18, 151 Cell Death, 146, 151, 163 Cell Differentiation, 151, 186, 188 Cell Division, 124, 147, 151, 164, 171, 173, 180, 182 Cell Fusion, 151, 183 Cell membrane, 151, 157, 168 Cell proliferation, 5, 6, 151, 186 Cell Respiration, 151, 184 Cell Survival, 151, 164 Cell Transplantation, 10, 50, 130, 152 Central Nervous System, 149, 152, 158, 163, 167, 176 Cerebellar, 147, 152, 184 Cerebral, 4, 36, 37, 56, 58, 59, 72, 87, 88, 147, 148, 149, 152, 159, 161, 187, 190 Cerebral Cortex, 147, 149, 152, 161 Cerebrospinal, 4, 152 Cerebrospinal fluid, 4, 152 Cerebrum, 152, 190, 192 Ceroid, 52, 152, 170 Cervical, 27, 37, 43, 152, 171 Cervix, 152 Character, 152, 156 Chemotactic Factors, 152, 154 Cherubism, 111, 112, 152 Chimera, 19, 152 Chin, 80, 152, 172 Cholesterol, 148, 152, 188 Chondrocytes, 152 Chondrogenesis, 19, 152 Chromatin, 146, 152, 175 Chromosomal, 145, 152, 153 Chromosome, 54, 58, 153, 169, 192

Index 197

Chronic, 56, 71, 102, 124, 153, 157, 159, 167, 169, 176, 181, 189 Chronic renal, 153, 181 Circulatory system, 153, 168 Cirrhosis, 153, 181 CIS, 7, 153, 184 C-kit receptor, 153, 188 Clathrin, 153, 159 Clinical Medicine, 61, 153, 181 Clinical trial, 4, 101, 103, 121, 153, 183 Cloning, 5, 9, 12, 148, 153 Clot Retraction, 153, 190 Coated Vesicles, 153, 159 Codon, 17, 153 Cofactor, 153, 182, 191 Collagen, 5, 7, 24, 39, 87, 145, 148, 153, 160, 161, 182 Collapse, 150, 154, 187 Coloboma, 154, 171 Colon, 124, 154, 169 Complement, 11, 145, 154, 162, 168 Complementary and alternative medicine, 97, 99, 154 Complementary medicine, 97, 154 Computational Biology, 121, 123, 154 Computed tomography, 75, 149, 154, 155 Computerized tomography, 154, 155 Concentric, 24, 155 Congenita, 3, 14, 62, 155, 158 Conjunctiva, 155, 192 Connective tissue, 5, 147, 149, 153, 155, 161, 170, 172, 185, 189, 190 Connective Tissue Cells, 155, 190 Constitutional, 27, 155 Contraindications, ii, 155 Coronary, 155, 172 Coronary Thrombosis, 155, 172 Corpus, 30, 155, 182 Corpus Callosum, 30, 155 Cortex, 48, 155, 177, 184 Cortical, 4, 27, 40, 49, 84, 87, 112, 155, 186, 190 Cortisone, 155, 181 Cranial, 13, 33, 40, 41, 89, 102, 112, 155, 160, 161, 168, 174, 176, 178, 179, 187, 192 Creatine, 41, 44, 58, 83, 155 Creatine Kinase, 44, 58, 83, 155 Creatinine, 155 Curative, 102, 156, 185, 190 Cyclic, 151, 156, 186 Cycloheximide, 16, 156 Cyclophosphamide, 102, 156

Cyst, 37, 156, 176 Cytokine, 6, 11, 15, 156 Cytoplasm, 146, 151, 156, 163, 175 Cytoskeleton, 8, 156, 168 Cytotoxic, 156, 183, 186 D De novo, 23, 156 Decompression, 33, 39, 45, 62, 63, 88, 156 Defense Mechanisms, 156, 168 Degenerative, 4, 42, 156, 176 Deletion, 8, 15, 17, 19, 22, 146, 156, 162 Dendrites, 156, 175 Dendritic, 90, 156, 171, 185 Dendritic cell, 90, 156 Density, 6, 11, 35, 149, 156, 176, 177 Dentists, 23, 156 Depersonalization, 156, 178 Depigmentation, 157, 194 Depolarization, 157, 186 Derealization, 156, 157, 178 Dermal, 157, 158 Diagnostic procedure, 105, 114, 157 Diastolic, 157, 165 Digestion, 106, 148, 149, 157, 168, 170, 188, 193 Digestive system, 103, 157, 173 Dilatation, 157, 182 Dimerization, 15, 157 Diploid, 157, 180, 192 Direct, iii, 6, 8, 151, 153, 157, 184, 189 Discrete, 149, 157, 190 Disease Progression, 102, 157 Dissociation, 144, 157 Distal, 27, 43, 67, 70, 147, 157, 183 Dizziness, 157, 178 Dorsal, 157, 181 Drive, ii, vi, 11, 91, 111, 157, 168 Duct, 151, 157, 185, 188 Duodenum, 148, 158, 188 Dwarfism, 19, 158 Dyes, 158, 175 Dysostosis, 26, 112, 158 Dysplasia, 41, 110, 111, 112, 125, 132, 158 Dyspnea, 158, 178 Dystrophy, 30, 60, 78, 124, 125, 158 E Ectoderm, 158 Ectodermal Dysplasia, 71, 124, 158 Ectopic, 26, 47, 158 Effector, 9, 154, 158 Effector cell, 158 Efferent, 158, 161

198 Osteopetrosis

Elastin, 153, 158, 160 Electrolysis, 145, 151, 158 Electrophysiological, 14, 158 Elementary Particles, 158, 175, 182 Embryo, 149, 151, 158, 163, 167, 177 Embryogenesis, 19, 158, 188 Emulsion, 158, 161 Endemic, 159, 188 Endocarditis, 62, 159 Endocardium, 159 Endocytosis, 14, 159 Endogenous, 16, 20, 159, 182, 192 Endosomes, 12, 159 Endothelial cell, 5, 159, 191 Endotoxin, 159, 192 End-stage renal, 153, 159, 181 Environmental Exposure, 159, 176 Environmental Health, 120, 122, 159 Enzymatic, 13, 145, 150, 154, 159, 184 Enzyme, 12, 143, 144, 158, 159, 162, 169, 172, 178, 182, 186, 189, 191, 192, 194 Epidemic, 159, 188 Epidemiological, 31, 74, 92, 159 Epidermis, 158, 159 Epinephrine, 159, 175, 193 Epiphyseal, 19, 48, 159 Epithelial, 5, 8, 14, 143, 159, 160 Epithelial Cells, 5, 14, 160 Erythroblasts, 160 Erythrocytes, 88, 145, 149, 160, 184 Erythroid Progenitor Cells, 38, 160 Erythropoietin, 40, 160 Esophagus, 157, 160, 188 Essential Tremor, 125, 160 Estrogens, 160, 163 Ethmoid, 160, 178 Eukaryotic Cells, 160, 166, 176 Excitability, 14, 160 Excrete, 160, 184 Exogenous, 23, 159, 160, 182 Expiration, 160, 184 Extensor, 160, 194 Extracellular, 10, 14, 19, 21, 159, 160, 161, 162, 168, 177, 187, 190 Extracellular Matrix, 21, 160, 161, 162, 168, 177 Extracellular Matrix Proteins, 160, 162 Extracellular Space, 10, 160, 161 F Facial, 40, 45, 70, 88, 111, 112, 161, 171, 179 Facial Expression, 161 Facial Nerve, 70, 88, 111, 161, 179

Failure to Thrive, 4, 161 Family Planning, 121, 161 Fat, 149, 161, 170, 185, 187 Femoral, 33, 46, 48, 71, 83, 161 Femur, 17, 98, 161, 191 Fetus, 149, 160, 161, 181, 193 Fibroblasts, 21, 57, 155, 161 Fibrosis, 125, 161, 185 Fibula, 161, 191 Fine-needle aspiration, 161, 174 Fissure, 154, 155, 161 Fixation, 109, 161 Focal Adhesions, 21, 161 Follicles, 23, 162 Fovea, 161, 162 Fracture Healing, 18, 162 G Gallbladder, 143, 157, 162 Gamma Rays, 162, 183 Gastric, 4, 162 Gastrin, 162, 165 Gastrointestinal, 11, 159, 162, 187, 189 Gelsolin, 22, 162 Gene Deletion, 22, 162 Gene Expression, 6, 7, 8, 17, 19, 126, 162 Gene Therapy, 6, 16, 162 Genetic Engineering, 148, 153, 162 Genetics, 4, 5, 10, 26, 27, 28, 31, 35, 38, 41, 42, 44, 50, 54, 58, 61, 66, 74, 85, 86, 130, 162 Genomics, 4, 162 Genotype, 10, 48, 162, 180 Germ Cells, 162, 171, 178, 190 Germ Layers, 149, 158, 163 Giant Cells, 24, 163, 185 Gland, 143, 155, 163, 170, 178, 179, 182, 186, 191 Glomerular, 163, 184 Glucocorticoid, 163, 181 Gluconeogenesis, 4, 163 Glucose, 42, 125, 144, 147, 163, 164, 167, 168, 185 Glutamic Acid, 163, 175, 182 Glycine, 145, 163, 175 Glycoprotein, 160, 163, 171, 190, 191, 192 Gonadal, 163, 188 Gonadotropin, 23, 163 Gonads, 163, 166 Gout, 112, 163 Governing Board, 163, 181 Graft, 81, 102, 163, 165, 166 Graft Rejection, 163, 166

Index 199

Grafting, 23, 163 Granulocytes, 163, 186, 194 Granuloma, 94, 163 Growth Disorders, 16, 164 Growth factors, 9, 164 Growth Plate, 19, 164 H Haptens, 144, 164 Helix-loop-helix, 15, 164 Hematopoiesis, 10, 45, 86, 102, 164 Heme, 164, 178 Hemoglobin, 145, 160, 164, 169 Hemoglobinopathies, 162, 164 Hemoglobinuria, 125, 164 Hemorrhage, 164, 188 Hemostasis, 164, 168 Hepatic, 16, 94, 164 Hereditary, 3, 80, 152, 158, 163, 164, 185 Heredity, 162, 164 Heterodimers, 164, 168 Heterogeneity, 31, 48, 49, 54, 59, 75, 93, 144, 164 Histiocytosis, 111, 164 Histology, 17, 59, 93, 165 Homeostasis, 9, 10, 16, 20, 21, 33, 85, 93, 149, 165 Homologous, 144, 162, 165, 189, 192 Hormonal, 6, 11, 31, 92, 147, 165 Host, 50, 102, 165, 166, 183, 193, 194 Humoral, 101, 163, 165, 191 Humour, 165 Hybrid, 20, 165 Hybridization, 6, 7, 151, 165 Hydrogen, 143, 148, 150, 160, 165, 173, 175, 180, 183 Hydrolysis, 12, 165, 168, 180, 182 Hydrops Fetalis, 62, 165 Hydroxylation, 150, 165 Hydroxylysine, 154, 165 Hydroxyproline, 89, 145, 154, 165 Hypercalcemia, 16, 111, 165 Hyperostosis, 111, 112, 165 Hypersensitivity, 165, 185 Hypertension, 11, 78, 165, 181 Hyperthyroidism, 110, 112, 165 Hypertrophy, 11, 112, 165 Hyperuricemia, 163, 165 Hypogonadism, 51, 166 Hypoplasia, 158, 166, 171 I Id, 95, 99, 131, 138, 140, 166 Idiopathic, 63, 166, 185

Immune response, 146, 155, 163, 164, 166, 189, 193, 194 Immune Sera, 166 Immune system, 21, 146, 148, 158, 166, 170, 180, 194 Immunization, 106, 166 Immunodeficiency, 35, 49, 71, 81, 124, 166 Immunoglobulin, 41, 146, 166, 173 Immunohistochemistry, 8, 15, 166 Immunologic, 144, 152, 166, 170, 183 Immunology, 144, 166 Immunosuppressive, 156, 163, 166 Immunosuppressive therapy, 166 Immunotherapy, 11, 148, 166 Immunotoxin, 11, 166 Impairment, 147, 166, 172 In situ, 6, 7, 8, 18, 24, 166 In Situ Hybridization, 6, 7, 8, 166 In vitro, 7, 15, 19, 21, 22, 23, 55, 151, 162, 166 In vivo, 5, 7, 8, 21, 22, 23, 151, 162, 166 Incisor, 5, 8, 167 Incontinentia Pigmenti, 71, 167 Incus, 109, 167, 171, 188 Indicative, 167, 179, 193 Induction, 6, 16, 20, 25, 52, 167 Infancy, 3, 68, 71, 167, 185 Infant Mortality, 132, 167 Infarction, 155, 167, 172 Infection, 102, 106, 147, 148, 152, 166, 167, 170, 185, 189, 194 Inflammation, 106, 146, 147, 161, 167, 176, 177, 181, 183, 185, 188, 190 Infusion, 167, 192 Initiation, 167, 188, 192 Inlay, 167, 184 Inner ear, 167, 171 Innervation, 161, 167, 171 Inorganic, 24, 167 Insight, 12, 13, 16, 22, 23, 167 Insulin, 11, 167, 168, 178 Insulin-dependent diabetes mellitus, 167, 168 Integrins, 5, 22, 162, 168 Interferon, 10, 13, 55, 57, 62, 80, 93, 101, 102, 114, 131, 168 Interferon-alpha, 168 Interstitial, 23, 161, 168, 184 Intestinal, 150, 168, 171 Intestine, 5, 149, 168, 169 Intracellular, 12, 14, 19, 153, 167, 168, 172, 185, 186

200 Osteopetrosis

Intracranial Pressure, 33, 168, 176 Intravenous, 49, 167, 168 Intrinsic, 144, 148, 168 Intubation, 43, 151, 168 Involuntary, 148, 160, 168, 174 Ion Channels, 168 Ion Transport, 14, 168 Ionizing, 144, 159, 168, 183 Ions, 14, 24, 143, 148, 157, 162, 165, 168, 169 Ischemia, 147, 169, 176 Isoenzyme, 41, 44, 58, 83, 155, 169 Isozymes, 45, 169 J Joint, 4, 7, 46, 50, 74, 79, 84, 112, 147, 169, 176, 189 K Kb, 120, 169 Kidney Disease, 70, 103, 120, 125, 169 Kinetics, 14, 169 L Labile, 154, 169 Labyrinth, 167, 169, 177, 194 Lacrimal, 161, 169 Large Intestine, 157, 168, 169, 184, 187 Lens, 155, 169, 184 Lethal, 29, 48, 54, 69, 124, 169 Leucine, 15, 169 Leukemia, 25, 56, 124, 162, 169 Leukocytes, 149, 152, 163, 168, 169, 175, 192 Library Services, 138, 169 Ligament, 169, 182 Ligands, 168, 169 Linkage, 5, 59, 79, 169, 180 Lip, 112, 169 Lipid, 152, 167, 170 Lipofuscin, 152, 170 Litter, 23, 170 Liver, 8, 54, 143, 148, 150, 153, 156, 157, 159, 160, 162, 164, 170, 181, 185 Localization, 54, 166, 170 Localized, 21, 161, 167, 170, 177, 180 Loop, 170 Lymph, 147, 152, 153, 159, 165, 170, 185 Lymph node, 147, 152, 170, 185 Lymphatic, 167, 170, 172, 188, 191 Lymphatic system, 170, 188, 191 Lymphedema, 71, 124, 170 Lymphocyte, 42, 102, 146, 170 Lymphoid, 146, 170 Lymphokines, 170

Lymphoma, 62, 78, 124, 170 Lysophospholipids, 106, 170 M Macrophage, 13, 17, 18, 38, 42, 55, 60, 90, 94, 106, 170 Macrophage Activation, 42, 170 Macrophage Colony-Stimulating Factor, 38, 90, 94, 170 Malabsorption, 125, 171 Malignancy, 62, 111, 171 Malignant tumor, 171, 173 Malleus, 109, 167, 171 Malnutrition, 23, 147, 171, 174 Mammogram, 150, 171, 172 Mandible, 64, 67, 74, 75, 145, 152, 171, 184 Mandibulofacial Dysostosis, 112, 171 Manifest, 9, 147, 171 Mastication, 171, 192 Masticatory, 112, 171 Maxillary, 58, 171, 178 Medial, 160, 171, 176, 187, 191 Median Nerve, 151, 171 Mediate, 12, 171 MEDLINE, 121, 123, 125, 171 Medullary, 78, 171 Megakaryocytes, 171, 191 Meiosis, 171, 189 Melanin, 157, 171, 172, 180, 193 Melanocytes, 15, 24, 171, 172 Melanoma, 124, 172 Melanosomes, 171, 172 Membrane, 5, 7, 12, 21, 151, 153, 154, 155, 157, 159, 160, 161, 168, 172, 173, 176, 182, 184, 186, 192, 193 Membrane Proteins, 172, 182 Mental, iv, 4, 69, 72, 103, 120, 122, 126, 152, 157, 172, 183, 193 Mental Disorders, 103, 172, 183 Mental Retardation, 4, 69, 72, 126, 172 Mesenchymal, 171, 172 Metabolic disorder, 163, 172 Metastasis, 172, 174 Metastatic, 14, 18, 20, 172 Metastatic cancer, 14, 172 Methylprednisolone, 49, 59, 172 MI, 14, 15, 24, 64, 66, 87, 110, 141, 172 Microbe, 172, 191 Microbiology, 92, 143, 172 Microcalcifications, 150, 172 Microfilaments, 161, 172 Microorganism, 153, 172, 194 Migration, 21, 170, 173

Index 201

Milliliter, 149, 173 Mineralization, 79, 173, 177 Mitosis, 147, 173 Mobility, 22, 173 Mobilization, 36, 173 Modification, 15, 145, 162, 173 Molecule, 146, 148, 154, 157, 158, 164, 165, 173, 175, 183, 186, 193 Monitor, 34, 101, 155, 173, 175 Monoclonal, 15, 81, 173 Monocyte, 18, 88, 171, 173 Mononuclear, 42, 47, 81, 163, 170, 173, 192 Morphogenesis, 8, 173 Morphological, 74, 158, 171, 173 Morphology, 7, 8, 63, 170, 173 Motility, 22, 162, 173 Mucosa, 111, 173, 174, 189 Mucositis, 173, 191 Multiple Myeloma, 20, 173 Muscle Fibers, 173, 174 Muscle Relaxation, 173, 174 Muscular Atrophy, 125, 174 Muscular Diseases, 174, 178 Muscular Dystrophies, 158, 174 Myeloma, 110, 174 Myocardium, 172, 174 Myotonia, 14, 174 Myotonic Dystrophy, 125, 174 N Nasal Cavity, 174, 178 Nausea, 174, 178, 193 NCI, 1, 103, 119, 153, 174 Need, 3, 24, 109, 110, 133, 153, 174 Needle biopsy, 43, 161, 174 Neonatal, 11, 23, 56, 93, 167, 174 Neoplasia, 124, 174 Neoplasms, 146, 151, 174, 183, 190 Neoplastic, 170, 174 Nephropathy, 169, 174 Nervous System, 30, 87, 125, 143, 152, 174, 175, 179 Neural, 143, 165, 174 Neuralgia, 69, 174 Neuromuscular, 78, 175, 178 Neuronal, 52, 86, 175 Neurons, 12, 156, 175, 189 Neurotransmitter, 143, 145, 151, 163, 168, 175, 185, 186, 187, 189 Neutrons, 144, 175, 183 Neutrophils, 41, 163, 169, 175 Nitrogen, 156, 160, 161, 175, 192

Nuclear, 25, 26, 32, 34, 35, 45, 64, 65, 67, 74, 76, 79, 82, 83, 86, 94, 148, 160, 162, 175, 185, 193 Nuclear Medicine, 26, 32, 34, 35, 45, 65, 67, 74, 76, 79, 82, 83, 86, 175 Nuclei, 144, 145, 162, 173, 175, 176, 182 Nucleic acid, 150, 165, 166, 175 Nucleic Acid Hybridization, 165, 175 Nucleocapsid, 64, 175 Nucleus, 146, 148, 152, 156, 158, 160, 162, 171, 173, 175, 182, 183, 190 O Occupational Therapy, 131, 175 Oncogene, 16, 22, 124, 175, 188 Oncogenic, 8, 168, 176 Opacity, 156, 176 Ophthalmic, 30, 42, 176 Ophthalmology, 38, 40, 81, 82, 90, 161, 176 Optic Atrophy, 79, 176 Optic Chiasm, 176 Optic Disk, 176 Optic Nerve, 39, 176, 184, 185 Oral Health, 112, 176 Organ Culture, 5, 176 Organelles, 153, 156, 171, 172, 176 Osseointegration, 149, 176 Ossicle, 97, 176 Ossification, 19, 176, 177, 185 Osteitis Deformans, 112, 176 Osteitis Fibrosa Cystica, 111, 176 Osteoarthritis, 42, 63, 112, 176 Osteoblasts, 5, 6, 7, 9, 19, 21, 23, 24, 177 Osteocalcin, 7, 40, 49, 93, 177 Osteoclasts, 6, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 47, 64, 89, 150, 177 Osteodystrophy, 111, 177 Osteogenesis, 110, 111, 112, 130, 149, 152, 177 Osteolysis, 18, 20, 26, 177 Osteolytic, 20, 177 Osteomalacia, 82, 93, 97, 112, 150, 177 Osteomyelitis, 12, 28, 47, 52, 58, 64, 65, 67, 71, 74, 75, 80, 82, 98, 177 Osteoporosis, 7, 8, 9, 10, 14, 15, 16, 17, 18, 20, 21, 24, 66, 85, 110, 112, 130, 149, 177 Osteosclerosis, 11, 50, 65, 77, 78, 177 Osteotomy, 53, 90, 177 Otolaryngologist, 111, 177 Otolaryngology, 49, 56, 65, 85, 109, 111, 177 Otosclerosis, 109, 177

202 Osteopetrosis

Outpatient, 11, 177 Ovarian Follicle, 177, 190 Ovaries, 23, 177 Ovary, 23, 145, 163, 177, 178, 189 Oxygen Consumption, 42, 178, 184 Oxygenase, 17, 178 P Palate, 112, 178 Palliative, 178, 190 Palsy, 45, 70, 178 Pancreas, 143, 144, 157, 167, 178, 187 Pancreatic, 11, 124, 178 Pancreatic cancer, 11, 124, 178 Pancreatic Hormones, 11, 178 Pancreatic Polypeptide, 178 Panic, 11, 178 Panic Disorder, 11, 178 Paradoxical, 82, 178 Paranasal Sinuses, 66, 178 Paraplegia, 67, 178 Parathyroid, 7, 10, 27, 44, 52, 54, 85, 150, 178, 179, 185, 190 Parathyroid Glands, 178, 179, 185 Parathyroid hormone, 7, 10, 27, 44, 52, 54, 85, 150, 179 Paresthesias, 178, 179 Parotid, 14, 179, 185 Paroxysmal, 69, 125, 179 Pathogenesis, 12, 14, 19, 75, 77, 81, 84, 86, 87, 111, 179 Pathologic, 4, 14, 111, 143, 147, 148, 149, 150, 155, 165, 179, 184, 187 Pathologic fracture, 14, 179 Pathologic Processes, 147, 179 Pathologies, 111, 179 Pathophysiology, 3, 11, 12, 50, 80, 179 Patient Education, 130, 136, 138, 141, 179 Pelvic, 26, 179, 182 Pelvis, 178, 179, 193 Peptide, 10, 106, 145, 150, 178, 179, 182 Perception, 11, 156, 179 Perfusion, 179, 191 Periodontal disease, 28, 179 Peripheral blood, 47, 168, 179 Peripheral Nervous System, 175, 178, 179, 180, 187, 189 Peripheral Nervous System Diseases, 178, 180 PH, 79, 149, 180 Phagocyte, 170, 180 Phallic, 161, 180 Phantom, 112, 180

Pharmacologic, 180, 191 Phenotype, 6, 8, 10, 15, 24, 42, 48, 84, 92, 162, 180 Phenylalanine, 180, 193 Phosphatidic Acids, 170, 180 Phospholipases, 180, 186 Phosphorus, 150, 179, 180 Phosphorylate, 24, 180 Phosphorylated, 15, 180 Phosphorylation, 15, 24, 180 Physiologic, 74, 78, 93, 144, 180, 183, 184 Physiology, 5, 10, 12, 15, 158, 180 Pigmentation, 15, 180 Plants, 150, 163, 173, 180, 185, 191 Plasma, 59, 78, 93, 146, 150, 151, 161, 164, 173, 174, 178, 180, 181, 186, 191 Plasma cells, 146, 173, 174, 181 Platelet Activation, 181, 186 Platelets, 181, 190 Pneumonia, 155, 181 Polyarthritis, 112, 181 Polycystic, 125, 181 Polymorphic, 5, 152, 181 Polymorphism, 55, 181 Polysaccharide, 146, 181 Portal Hypertension, 78, 181 Portal Vein, 181 Posterior, 27, 78, 145, 147, 157, 178, 181, 187 Postmenopausal, 177, 181 Postsynaptic, 181, 186 Potentiation, 181, 186 Practice Guidelines, 122, 181 Precursor, 17, 21, 145, 152, 156, 158, 159, 180, 181, 192, 193 Prednisolone, 172, 181 Prednisone, 29, 53, 86, 131, 181 Prenatal, 75, 78, 79, 158, 181 Presumptive, 37, 182 Probe, 10, 182 Progesterone, 182, 188 Progression, 101, 145, 182 Progressive, 13, 151, 153, 163, 174, 176, 181, 182, 184 Projection, 156, 176, 182, 184 Proline, 21, 153, 165, 182 Promoter, 7, 16, 22, 182 Prophase, 182, 189 Prophylaxis, 182, 193 Prostate, 11, 124, 182 Protein Binding, 182, 191 Protein C, 10, 145, 153, 177, 182, 194

Index 203

Protein S, 6, 110, 125, 126, 148, 156, 177, 182, 188 Proteinuria, 173, 182 Proteolytic, 154, 182 Proton Pump, 42, 62, 182 Protons, 12, 14, 144, 165, 168, 182, 183 Proximal, 67, 70, 157, 174, 183 Psychiatry, 33, 73, 161, 183 Psychic, 172, 183, 186 Public Policy, 121, 183 Pulse, 173, 183 Pyogenic, 177, 183 Q Quiescent, 183, 194 R Race, 173, 183 Radiation, 54, 158, 159, 162, 168, 180, 183, 194 Radiation Hybrid Mapping, 54, 183 Radioactive, 149, 165, 175, 176, 183, 190, 193 Radioimmunotherapy, 183 Radiological, 31, 76, 80, 83, 84, 89, 94, 183 Radiotherapy, 102, 183 Randomized, 13, 102, 183 Receptor, 7, 8, 10, 15, 18, 20, 22, 23, 24, 55, 143, 146, 153, 171, 183, 186 Recombinant, 5, 13, 17, 24, 40, 55, 80, 93, 114, 184, 193 Recombination, 162, 184 Rectum, 146, 149, 154, 157, 169, 182, 184 Red blood cells, 160, 178, 184, 185 Red Nucleus, 147, 184 Refer, 1, 154, 157, 161, 170, 175, 183, 184, 194 Refraction, 184, 187 Regimen, 102, 184 Relapse, 102, 184 Renal failure, 85, 184 Renal tubular, 4, 12, 27, 36, 37, 45, 58, 70, 71, 72, 81, 88, 184 Renal tubular acidosis, 4, 12, 27, 36, 37, 45, 58, 70, 71, 72, 81, 88, 184 Resection, 71, 184 Resolving, 28, 184 Respiration, 4, 146, 150, 173, 184 Restoration, 6, 45, 162, 184, 194 Retina, 169, 176, 184, 185 Retinal, 81, 176, 184, 185 Retinal Ganglion Cells, 176, 185 Retinoblastoma, 124, 185 Retroviral vector, 162, 185

Rheumatism, 28, 185 Rheumatoid, 9, 20, 112, 185 Rheumatoid arthritis, 9, 20, 112, 185 Ribose, 143, 185 Rickets, 30, 52, 57, 66, 71, 82, 93, 97, 112, 150, 185 Rigidity, 24, 168, 180, 185 Risk factor, 110, 185 S Salivary, 157, 161, 178, 185 Salivary glands, 157, 161, 185 Saponins, 185, 188 Sarcoidosis, 111, 185 Scatter, 180, 185 Sclerosis, 38, 125, 185 Scoliosis, 78, 185 Screening, 6, 10, 153, 185 Second Messenger Systems, 185 Secretion, 5, 21, 23, 158, 165, 168, 185, 186, 193 Seizures, 179, 186 Semen, 182, 186 Senile, 177, 186 Sepsis, 46, 186 Sequence Analysis, 16, 186 Serous, 165, 186 Serum, 8, 44, 55, 83, 88, 94, 145, 154, 155, 163, 166, 177, 186, 192 Sex Determination, 125, 186 Shock, 186, 192 Side effect, 148, 156, 166, 186, 191 Signal Transduction, 4, 186 Signs and Symptoms, 184, 186 Skeleton, 19, 31, 132, 143, 149, 161, 169, 186, 187, 191 Skull, 5, 41, 168, 187, 190 Skull Base, 5, 187 Sleep apnea, 82, 83, 187 Small intestine, 158, 165, 168, 187 Sodium, 163, 187 Soft tissue, 149, 187 Somatic, 151, 158, 165, 171, 173, 179, 187 Somatostatin, 178, 187 Specialist, 133, 187 Species, 16, 144, 152, 159, 165, 171, 173, 183, 187, 189, 192, 194 Specificity, 144, 187, 191 Spectrum, 43, 86, 187 Sperm, 153, 187 Sphenoid, 178, 187 Spinal cord, 152, 171, 174, 178, 179, 180, 187

204 Osteopetrosis

Spinal Cord Diseases, 178, 187 Spleen, 26, 170, 185, 188 Splenomegaly, 177, 188 Spondylitis, 112, 188 Spondylolysis, 71, 84, 188 Sporadic, 70, 79, 185, 188 Stapes, 109, 167, 188 Stem Cell Factor, 15, 153, 188 Stem cell transplantation, 49, 188 Stem Cells, 130, 144, 160, 188 Stenosis, 78, 82, 188 Sterile, 8, 147, 179, 188 Sterility, 156, 188 Steroid, 9, 145, 155, 185, 188 Stomach, 5, 143, 157, 160, 162, 165, 174, 187, 188 Stool, 87, 154, 169, 188 Streptomycin, 156, 188 Stress, 7, 84, 174, 185, 188 Stria, 60, 65, 89, 188 Stricture, 188 Stroke, 56, 103, 120, 188 Stromal, 7, 21, 189 Stromal Cells, 7, 21, 189 Structure-Activity Relationship, 10, 189 Subacute, 167, 189 Subclinical, 167, 186, 189 Subspecies, 187, 189 Substance P, 186, 188, 189 Substrate, 15, 18, 22, 161, 189 Subtrochanteric, 98, 189 Superoxide, 85, 94, 106, 189 Support group, 132, 189 Symphysis, 152, 182, 189 Synapse, 189 Synapsis, 189 Synaptic, 25, 175, 186, 189 Syncytium, 163, 189 Systemic, 39, 111, 112, 149, 159, 167, 181, 185, 189, 192 Systemic disease, 111, 112, 189 Systolic, 165, 189 T Talus, 189, 191 Technetium, 34, 190 Telangiectasia, 125, 190 Telencephalon, 148, 152, 190 Temporal, 8, 16, 66, 69, 85, 87, 110, 111, 145, 190 Tendinitis, 70, 190 Tendon, 190 Terminator, 153, 190

Testicular, 16, 190 Testis, 145, 163, 190 Testosterone, 145, 190 Tetany, 179, 190 Thalamic, 25, 147, 190 Thalamic Diseases, 147, 190 Theca Cells, 23, 190 Therapeutics, 16, 190 Thigh, 161, 190 Threshold, 160, 165, 190 Thrombasthenia, 66, 190 Thrombin, 182, 191 Thrombocytopenia, 40, 83, 191 Thrombomodulin, 182, 191 Thrombopoietin, 38, 191 Thrombosis, 168, 182, 188, 191 Thymidine, 7, 17, 191 Thymus, 88, 166, 170, 191 Thyroid, 39, 42, 78, 86, 88, 150, 165, 178, 179, 191, 193 Thyroid Gland, 165, 178, 179, 191 Thyroid Hormones, 39, 86, 191, 193 Tibia, 53, 161, 191 Tin, 151, 191 Tissue Distribution, 15, 191 Tomography, 154, 155, 191 Tooth Preparation, 143, 191 Toxic, iv, 144, 159, 166, 191 Toxicity, 16, 191 Toxicology, 122, 191 Toxins, 146, 167, 176, 183, 191 Trachea, 191, 192 Transcription Factors, 19, 192 Transduction, 186, 192 Transfection, 148, 162, 192 Transfer Factor, 166, 192 Transferases, 16, 192 Transfusion, 41, 88, 192 Translation, 145, 192 Translational, 15, 192 Translocating, 12, 192 Transplantation, 4, 11, 13, 29, 34, 35, 36, 43, 46, 49, 50, 51, 53, 55, 57, 58, 60, 75, 81, 82, 84, 89, 93, 102, 130, 131, 149, 153, 166, 192 Trauma, 46, 47, 69, 71, 83, 148, 190, 192 Treatment Failure, 102, 192 Trigeminal, 69, 192 Trisomy, 112, 192 Tryptophan, 154, 192 Tuberous Sclerosis, 125, 192 Tumor Necrosis Factor, 20, 192

Index 205

Tunica, 173, 193 Tympani, 171, 193 Tympanic membrane, 171, 193 Tyrosine, 7, 8, 21, 22, 23, 87, 193 U Unconscious, 156, 166, 193 Uranium, 190, 193 Uremia, 184, 193 Urethra, 182, 193 Uric, 163, 165, 193 Urinary, 12, 72, 89, 150, 193 Urine, 52, 92, 148, 155, 164, 182, 193 Uterus, 152, 155, 178, 182, 193 V Vaccination, 11, 106, 193 Vaccines, 193, 194 Vacuoles, 159, 176, 193 Vascular, 11, 167, 177, 188, 191, 193 Vector, 106, 192, 193 Vein, 168, 175, 179, 181, 193 Venous, 56, 182, 193 Ventricles, 152, 193 Venules, 149, 150, 193 Vertebrae, 7, 11, 38, 187, 188, 193 Vertebral, 27, 84, 193 Vesicular, 12, 193

Vestibular, 111, 194 Vestibule, 167, 194 Veterinary Medicine, 121, 194 Viral, 16, 64, 150, 163, 176, 192, 194 Viral vector, 16, 194 Virion, 175, 194 Virulence, 191, 194 Virus, 11, 25, 51, 92, 150, 162, 163, 168, 175, 185, 192, 194 Vitiligo, 59, 194 Vitro, 8, 22, 23, 194 Vivo, 5, 8, 13, 21, 194 W Weight Gain, 161, 194 White blood cell, 146, 169, 170, 173, 174, 181, 194 Windpipe, 191, 194 Wound Healing, 168, 194 X Xenograft, 145, 194 X-ray, 14, 43, 79, 92, 149, 154, 155, 162, 171, 175, 183, 194 Y Yeasts, 180, 194 Z Zymogen, 182, 194

206 Osteopetrosis

Index 207

208 Osteopetrosis

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